Publisher: Sage Publications   (Total: 1166 journals)

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Showing 1 - 200 of 1166 Journals sorted alphabetically
AADE in Practice     Hybrid Journal   (Followers: 6)
Abstracts in Anthropology     Full-text available via subscription   (Followers: 29)
Academic Pathology     Open Access   (Followers: 6)
Accounting History     Hybrid Journal   (Followers: 18, SJR: 0.527, CiteScore: 1)
Acta Radiologica     Hybrid Journal   (Followers: 1, SJR: 0.754, CiteScore: 2)
Acta Radiologica Open     Open Access   (Followers: 2)
Acta Sociologica     Hybrid Journal   (Followers: 39, SJR: 0.939, CiteScore: 2)
Action Research     Hybrid Journal   (Followers: 53, SJR: 0.308, CiteScore: 1)
Active Learning in Higher Education     Hybrid Journal   (Followers: 398, SJR: 1.397, CiteScore: 2)
Adaptive Behavior     Hybrid Journal   (Followers: 9, SJR: 0.288, CiteScore: 1)
Administration & Society     Hybrid Journal   (Followers: 18, SJR: 0.675, CiteScore: 1)
Adoption & Fostering     Hybrid Journal   (Followers: 25, SJR: 0.313, CiteScore: 0)
Adsorption Science & Technology     Open Access   (Followers: 9, SJR: 0.258, CiteScore: 1)
Adult Education Quarterly     Hybrid Journal   (Followers: 262, SJR: 0.566, CiteScore: 2)
Adult Learning     Hybrid Journal   (Followers: 51)
Advances in Dental Research     Hybrid Journal   (Followers: 11, SJR: 1.791, CiteScore: 4)
Advances in Developing Human Resources     Hybrid Journal   (Followers: 35, SJR: 0.614, CiteScore: 2)
Advances in Mechanical Engineering     Open Access   (Followers: 156, SJR: 0.272, CiteScore: 1)
Advances in Methods and Practices in Psychological Science     Full-text available via subscription   (Followers: 20)
Advances in Structural Engineering     Full-text available via subscription   (Followers: 51, SJR: 0.599, CiteScore: 1)
AERA Open     Open Access   (Followers: 14)
Affilia     Hybrid Journal   (Followers: 6, SJR: 0.496, CiteScore: 1)
Africa Spectrum     Open Access   (Followers: 17)
Agrarian South : J. of Political Economy     Hybrid Journal   (Followers: 3)
Air, Soil & Water Research     Open Access   (Followers: 13, SJR: 0.214, CiteScore: 1)
Alexandria : The J. of National and Intl. Library and Information Issues     Full-text available via subscription   (Followers: 68)
Allergy & Rhinology     Open Access   (Followers: 5)
AlterNative : An Intl. J. of Indigenous Peoples     Full-text available via subscription   (Followers: 39, SJR: 0.194, CiteScore: 0)
Alternative Law J.     Hybrid Journal   (Followers: 12, SJR: 0.176, CiteScore: 0)
Alternatives : Global, Local, Political     Hybrid Journal   (Followers: 12, SJR: 0.351, CiteScore: 1)
Alternatives to Laboratory Animals     Full-text available via subscription   (Followers: 11, SJR: 0.297, CiteScore: 1)
American Behavioral Scientist     Hybrid Journal   (Followers: 26, SJR: 0.982, CiteScore: 2)
American Economist     Hybrid Journal   (Followers: 7)
American Educational Research J.     Hybrid Journal   (Followers: 260, SJR: 2.913, CiteScore: 3)
American J. of Alzheimer's Disease and Other Dementias     Hybrid Journal   (Followers: 23, SJR: 0.67, CiteScore: 2)
American J. of Cosmetic Surgery     Hybrid Journal   (Followers: 9)
American J. of Evaluation     Hybrid Journal   (Followers: 18, SJR: 0.646, CiteScore: 2)
American J. of Health Promotion     Hybrid Journal   (Followers: 35, SJR: 0.807, CiteScore: 1)
American J. of Hospice and Palliative Medicine     Hybrid Journal   (Followers: 47, SJR: 0.65, CiteScore: 1)
American J. of Law & Medicine     Full-text available via subscription   (Followers: 12, SJR: 0.204, CiteScore: 1)
American J. of Lifestyle Medicine     Hybrid Journal   (Followers: 7, SJR: 0.431, CiteScore: 1)
American J. of Medical Quality     Hybrid Journal   (Followers: 13, SJR: 0.777, CiteScore: 1)
American J. of Men's Health     Open Access   (Followers: 9, SJR: 0.595, CiteScore: 2)
American J. of Rhinology and Allergy     Hybrid Journal   (Followers: 11, SJR: 0.972, CiteScore: 2)
American J. of Sports Medicine     Hybrid Journal   (Followers: 249, SJR: 3.949, CiteScore: 6)
American Politics Research     Hybrid Journal   (Followers: 36, SJR: 1.313, CiteScore: 1)
American Review of Public Administration     Hybrid Journal   (Followers: 28, SJR: 2.062, CiteScore: 2)
American Sociological Review     Hybrid Journal   (Followers: 358, SJR: 6.333, CiteScore: 6)
American String Teacher     Full-text available via subscription   (Followers: 3)
Analytical Chemistry Insights     Open Access   (Followers: 26, SJR: 0.224, CiteScore: 1)
Angiology     Hybrid Journal   (Followers: 5, SJR: 0.849, CiteScore: 2)
Animation     Hybrid Journal   (Followers: 15, SJR: 0.197, CiteScore: 0)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 10, SJR: 0.634, CiteScore: 1)
Annals of Otology, Rhinology & Laryngology     Hybrid Journal   (Followers: 20, SJR: 0.807, CiteScore: 1)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 59, SJR: 1.096, CiteScore: 2)
Annals of the American Academy of Political and Social Science     Hybrid Journal   (Followers: 51, SJR: 1.225, CiteScore: 3)
Annals of the ICRP     Hybrid Journal   (Followers: 4, SJR: 0.548, CiteScore: 1)
Anthropocene Review     Hybrid Journal   (Followers: 8, SJR: 3.341, CiteScore: 7)
Anthropological Theory     Hybrid Journal   (Followers: 48, SJR: 0.739, CiteScore: 1)
Antitrust Bulletin     Hybrid Journal   (Followers: 14)
Antiviral Chemistry and Chemotherapy     Open Access   (Followers: 2, SJR: 0.635, CiteScore: 2)
Antyajaa : Indian J. of Women and Social Change     Hybrid Journal   (Followers: 1)
Applied Biosafety     Hybrid Journal   (Followers: 1, SJR: 0.131, CiteScore: 0)
Applied Psychological Measurement     Hybrid Journal   (Followers: 21, SJR: 1.17, CiteScore: 1)
Applied Spectroscopy     Full-text available via subscription   (Followers: 27, SJR: 0.489, CiteScore: 2)
Armed Forces & Society     Hybrid Journal   (Followers: 25, SJR: 0.29, CiteScore: 1)
Arthaniti : J. of Economic Theory and Practice     Full-text available via subscription  
Arts and Humanities in Higher Education     Hybrid Journal   (Followers: 49, SJR: 0.305, CiteScore: 1)
Asia Pacific Media Educator     Hybrid Journal   (Followers: 1, SJR: 0.23, CiteScore: 0)
Asia-Pacific J. of Management Research and Innovation     Full-text available via subscription   (Followers: 3)
Asia-Pacific J. of Public Health     Hybrid Journal   (Followers: 15, SJR: 0.558, CiteScore: 1)
Asia-Pacific J. of Rural Development     Hybrid Journal   (Followers: 2)
Asian and Pacific Migration J.     Full-text available via subscription   (Followers: 8, SJR: 0.324, CiteScore: 1)
Asian Cardiovascular and Thoracic Annals     Hybrid Journal   (Followers: 2, SJR: 0.305, CiteScore: 0)
Asian J. of Comparative Politics     Hybrid Journal   (Followers: 5)
Asian J. of Legal Education     Full-text available via subscription   (Followers: 4)
Asian J. of Management Cases     Hybrid Journal   (Followers: 6, SJR: 0.101, CiteScore: 0)
ASN Neuro     Open Access   (Followers: 2, SJR: 1.534, CiteScore: 3)
Assessment     Hybrid Journal   (Followers: 19, SJR: 1.519, CiteScore: 3)
Assessment for Effective Intervention     Hybrid Journal   (Followers: 15, SJR: 0.578, CiteScore: 1)
Australasian J. of Early Childhood     Hybrid Journal   (Followers: 7, SJR: 0.535, CiteScore: 1)
Australasian Psychiatry     Hybrid Journal   (Followers: 18, SJR: 0.433, CiteScore: 1)
Australian & New Zealand J. of Psychiatry     Hybrid Journal   (Followers: 30, SJR: 1.801, CiteScore: 2)
Australian and New Zealand J. of Criminology     Hybrid Journal   (Followers: 547, SJR: 0.612, CiteScore: 1)
Australian J. of Career Development     Hybrid Journal   (Followers: 5)
Australian J. of Education     Hybrid Journal   (Followers: 51, SJR: 0.403, CiteScore: 1)
Australian J. of Management     Hybrid Journal   (Followers: 13, SJR: 0.497, CiteScore: 1)
Autism     Hybrid Journal   (Followers: 358, SJR: 1.739, CiteScore: 4)
Autism & Developmental Language Impairments     Open Access   (Followers: 17)
Avian Biology Research     Hybrid Journal   (Followers: 6, SJR: 0.401, CiteScore: 1)
Behavior Modification     Hybrid Journal   (Followers: 14, SJR: 0.877, CiteScore: 2)
Behavioral and Cognitive Neuroscience Reviews     Hybrid Journal   (Followers: 27)
Behavioral Disorders     Hybrid Journal   (Followers: 2)
Beyond Behavior     Hybrid Journal   (Followers: 2)
Bible Translator     Hybrid Journal   (Followers: 13)
Biblical Theology Bulletin     Hybrid Journal   (Followers: 24, SJR: 0.184, CiteScore: 0)
Big Data & Society     Open Access   (Followers: 55)
Biochemistry Insights     Open Access   (Followers: 7)
Bioinformatics and Biology Insights     Open Access   (Followers: 12, SJR: 1.141, CiteScore: 2)
Biological Research for Nursing     Hybrid Journal   (Followers: 7, SJR: 0.685, CiteScore: 2)
Biomarker Insights     Open Access   (Followers: 1, SJR: 0.81, CiteScore: 2)
Biomarkers in Cancer     Open Access   (Followers: 11)
Biomedical Engineering and Computational Biology     Open Access   (Followers: 14)
Biomedical Informatics Insights     Open Access   (Followers: 8)
Bioscope: South Asian Screen Studies     Hybrid Journal   (Followers: 4, SJR: 0.235, CiteScore: 0)
BMS: Bulletin of Sociological Methodology/Bulletin de Méthodologie Sociologique     Hybrid Journal   (Followers: 4, SJR: 0.226, CiteScore: 0)
Body & Society     Hybrid Journal   (Followers: 29, SJR: 1.531, CiteScore: 3)
Bone and Tissue Regeneration Insights     Open Access   (Followers: 2)
Brain and Neuroscience Advances     Open Access  
Brain Science Advances     Open Access  
Breast Cancer : Basic and Clinical Research     Open Access   (Followers: 12, SJR: 0.823, CiteScore: 2)
British J. of Music Therapy     Hybrid Journal   (Followers: 9)
British J. of Occupational Therapy     Hybrid Journal   (Followers: 253, SJR: 0.323, CiteScore: 1)
British J. of Pain     Hybrid Journal   (Followers: 31, SJR: 0.579, CiteScore: 2)
British J. of Politics and Intl. Relations     Hybrid Journal   (Followers: 39, SJR: 0.91, CiteScore: 2)
British J. of Visual Impairment     Hybrid Journal   (Followers: 14, SJR: 0.337, CiteScore: 1)
British J.ism Review     Hybrid Journal   (Followers: 18)
BRQ Business Review Quarterly     Open Access   (Followers: 1)
Building Acoustics     Hybrid Journal   (Followers: 4, SJR: 0.215, CiteScore: 1)
Building Services Engineering Research & Technology     Hybrid Journal   (Followers: 3, SJR: 0.583, CiteScore: 1)
Bulletin of Science, Technology & Society     Hybrid Journal   (Followers: 9)
Business & Society     Hybrid Journal   (Followers: 15)
Business and Professional Communication Quarterly     Hybrid Journal   (Followers: 9, SJR: 0.348, CiteScore: 1)
Business Information Review     Hybrid Journal   (Followers: 17, SJR: 0.279, CiteScore: 0)
Business Perspectives and Research     Hybrid Journal   (Followers: 3)
Cahiers Élisabéthains     Hybrid Journal   (Followers: 1, SJR: 0.111, CiteScore: 0)
Calcutta Statistical Association Bulletin     Hybrid Journal   (Followers: 1)
California Management Review     Hybrid Journal   (Followers: 37, SJR: 2.209, CiteScore: 4)
Canadian Association of Radiologists J.     Full-text available via subscription   (Followers: 2, SJR: 0.463, CiteScore: 1)
Canadian J. of Kidney Health and Disease     Open Access   (Followers: 8, SJR: 1.007, CiteScore: 2)
Canadian J. of Nursing Research (CJNR)     Hybrid Journal   (Followers: 15)
Canadian J. of Occupational Therapy     Hybrid Journal   (Followers: 168, SJR: 0.626, CiteScore: 1)
Canadian J. of Psychiatry     Hybrid Journal   (Followers: 28, SJR: 1.769, CiteScore: 3)
Canadian J. of School Psychology     Hybrid Journal   (Followers: 12, SJR: 0.266, CiteScore: 1)
Canadian Pharmacists J. / Revue des Pharmaciens du Canada     Hybrid Journal   (Followers: 3, SJR: 0.536, CiteScore: 1)
Cancer Control     Open Access   (Followers: 2)
Cancer Growth and Metastasis     Open Access   (Followers: 1)
Cancer Informatics     Open Access   (Followers: 4, SJR: 0.64, CiteScore: 1)
Capital and Class     Hybrid Journal   (Followers: 10, SJR: 0.282, CiteScore: 1)
Cardiac Cath Lab Director     Full-text available via subscription   (Followers: 1)
Cardiovascular and Thoracic Open     Open Access   (Followers: 1)
Career Development and Transition for Exceptional Individuals     Hybrid Journal   (Followers: 10, SJR: 0.44, CiteScore: 1)
Cartilage     Hybrid Journal   (Followers: 6, SJR: 0.889, CiteScore: 3)
Cell Transplantation     Open Access   (Followers: 5, SJR: 1.023, CiteScore: 3)
Cephalalgia     Hybrid Journal   (Followers: 8, SJR: 1.581, CiteScore: 3)
Cephalalgia Reports     Open Access   (Followers: 4)
Child Language Teaching and Therapy     Hybrid Journal   (Followers: 34, SJR: 0.501, CiteScore: 1)
Child Maltreatment     Hybrid Journal   (Followers: 11, SJR: 1.22, CiteScore: 3)
Child Neurology Open     Open Access   (Followers: 6)
Childhood     Hybrid Journal   (Followers: 19, SJR: 0.894, CiteScore: 2)
Childhood Obesity and Nutrition     Open Access   (Followers: 12)
China Information     Hybrid Journal   (Followers: 9, SJR: 0.767, CiteScore: 2)
China Report     Hybrid Journal   (Followers: 11, SJR: 0.221, CiteScore: 0)
Chinese J. of Sociology     Full-text available via subscription   (Followers: 5)
Christian Education J. : Research on Educational Ministry     Hybrid Journal   (Followers: 1)
Chronic Illness     Hybrid Journal   (Followers: 6, SJR: 0.672, CiteScore: 2)
Chronic Respiratory Disease     Hybrid Journal   (Followers: 12, SJR: 0.808, CiteScore: 2)
Chronic Stress     Open Access  
Citizenship, Social and Economics Education     Full-text available via subscription   (Followers: 6, SJR: 0.145, CiteScore: 0)
Cleft Palate-Craniofacial J.     Hybrid Journal   (Followers: 8, SJR: 0.757, CiteScore: 1)
Clin-Alert     Hybrid Journal   (Followers: 1)
Clinical and Applied Thrombosis/Hemostasis     Open Access   (Followers: 32, SJR: 0.49, CiteScore: 1)
Clinical and Translational Neuroscience     Open Access   (Followers: 1)
Clinical Case Studies     Hybrid Journal   (Followers: 3, SJR: 0.364, CiteScore: 1)
Clinical Child Psychology and Psychiatry     Hybrid Journal   (Followers: 45, SJR: 0.73, CiteScore: 2)
Clinical EEG and Neuroscience     Hybrid Journal   (Followers: 8, SJR: 0.552, CiteScore: 2)
Clinical Ethics     Hybrid Journal   (Followers: 13, SJR: 0.296, CiteScore: 1)
Clinical Medicine Insights : Arthritis and Musculoskeletal Disorders     Open Access   (Followers: 3, SJR: 0.537, CiteScore: 2)
Clinical Medicine Insights : Blood Disorders     Open Access   (Followers: 1, SJR: 0.314, CiteScore: 2)
Clinical Medicine Insights : Cardiology     Open Access   (Followers: 8, SJR: 0.686, CiteScore: 2)
Clinical Medicine Insights : Case Reports     Open Access   (Followers: 1, SJR: 0.283, CiteScore: 1)
Clinical Medicine Insights : Circulatory, Respiratory and Pulmonary Medicine     Open Access   (Followers: 4, SJR: 0.425, CiteScore: 2)
Clinical Medicine Insights : Ear, Nose and Throat     Open Access   (Followers: 2)
Clinical Medicine Insights : Endocrinology and Diabetes     Open Access   (Followers: 34, SJR: 0.63, CiteScore: 2)
Clinical Medicine Insights : Oncology     Open Access   (Followers: 3, SJR: 1.129, CiteScore: 3)
Clinical Medicine Insights : Pediatrics     Open Access   (Followers: 3)
Clinical Medicine Insights : Psychiatry     Open Access   (Followers: 10)
Clinical Medicine Insights : Reproductive Health     Open Access   (Followers: 1, SJR: 0.776, CiteScore: 0)
Clinical Medicine Insights : Therapeutics     Open Access   (Followers: 1, SJR: 0.172, CiteScore: 0)
Clinical Medicine Insights : Trauma and Intensive Medicine     Open Access   (Followers: 4)
Clinical Medicine Insights : Urology     Open Access   (Followers: 3)
Clinical Medicine Insights : Women's Health     Open Access   (Followers: 4)
Clinical Nursing Research     Hybrid Journal   (Followers: 34, SJR: 0.471, CiteScore: 1)
Clinical Pathology     Open Access   (Followers: 5)
Clinical Pediatrics     Hybrid Journal   (Followers: 25, SJR: 0.487, CiteScore: 1)
Clinical Psychological Science     Hybrid Journal   (Followers: 16, SJR: 3.281, CiteScore: 5)
Clinical Rehabilitation     Hybrid Journal   (Followers: 78, SJR: 1.322, CiteScore: 3)
Clinical Risk     Hybrid Journal   (Followers: 5, SJR: 0.133, CiteScore: 0)
Clinical Trials     Hybrid Journal   (Followers: 22, SJR: 2.399, CiteScore: 2)
Clothing and Textiles Research J.     Hybrid Journal   (Followers: 28, SJR: 0.36, CiteScore: 1)
Collections : A J. for Museum and Archives Professionals     Full-text available via subscription   (Followers: 3)
Common Law World Review     Full-text available via subscription   (Followers: 17)
Communication & Sport     Hybrid Journal   (Followers: 8, SJR: 0.385, CiteScore: 1)
Communication and the Public     Hybrid Journal   (Followers: 2)
Communication Disorders Quarterly     Hybrid Journal   (Followers: 15, SJR: 0.458, CiteScore: 1)
Communication Research     Hybrid Journal   (Followers: 24, SJR: 2.171, CiteScore: 3)
Community College Review     Hybrid Journal   (Followers: 8, SJR: 1.451, CiteScore: 1)
Comparative Political Studies     Hybrid Journal   (Followers: 293, SJR: 3.772, CiteScore: 3)
Compensation & Benefits Review     Hybrid Journal   (Followers: 8)
Competition & Change     Hybrid Journal   (Followers: 12, SJR: 0.843, CiteScore: 2)

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Similar Journals
Journal Cover
Annals of Pharmacotherapy
Journal Prestige (SJR): 1.096
Citation Impact (citeScore): 2
Number of Followers: 59  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1060-0280 - ISSN (Online) 1542-6270
Published by Sage Publications Homepage  [1166 journals]
  • Peripherally Infused Norepinephrine to Avoid Central Venous Catheter
           Placement in a Medical Intensive Care Unit: A Pilot Study

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      Authors: Lara M. Groetzinger, Julia Williams, Susan Svec, Michael P. Donahoe, Phillip E. Lamberty, Ian J. Barbash
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Reducing central venous catheter (CVC) utilization can reduce complications in the intensive care unit (ICU). While norepinephrine (NE) is traditionally administered via a CVC, lower concentrations may be safely administered via peripheral intravenous (PIV) lines.Objective:We aimed to describe the implementation of a pilot protocol utilizing PIVs to administer a low-dose and lower-concentration NE, review the number of CVCs avoided, and evaluate any adverse events.Methods:In a quaternary medical intensive care unit (MICU), from March 1, 2019, to February 29, 2020, we reviewed charts for CVC placement and adverse events from the pNE infusion. We also measured unit-level CVC utilization in all MICU patients and assessed the change in utilization associated with the peripheral norepinephrine (pNE) protocol.Results:Over a 1-year period, 87 patients received a pNE infusion. Overall, 44 patients (51%) never required CVC placement during their MICU stay. Three patients (3%) experienced adverse events, none of which were documented as serious and or required antidote for treatment. Implementation of the protocol was associated with a decrease in the number of patients at the unit level who received CVCs, even if they did not receive pNE.Conclusion and Relevance:In this small pilot study, we pragmatically demonstrated that pNE is safe and may reduce the need for CVC placement. This information can be used to aid in pNE protocol development and implementation at other institutions, but further research should be done to confirm the safety of routine use of pNE in clinical practice.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-22T04:29:38Z
      DOI: 10.1177/10600280211053318
       
  • Hemodynamic Effects of Ketamine Compared With Propofol or Dexmedetomidine
           as Continuous ICU Sedation

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      Authors: Evan Atchley, Eljim Tesoro, Robert Meyer, Alexia Bauer, Mark Pulver, Scott Benken
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundKetamine has seen increased use for sedation in the intensive care unit. In contrast to propofol or dexmedetomidine, ketamine may provide a positive effect on hemodynamics.ObjectiveThe objective of this study was to compare the development of clinically significant hypotension or bradycardia (ie, negative hemodynamic event) between critically ill adults receiving sedation with ketamine and either propofol or dexmedetomidine.MethodsThis was a retrospective cohort study of adults admitted to an intensive care unit at an academic medical center between January 2016 and January 2021.ResultsPatients in the ketamine group (n = 78) had significantly less clinically significant hypotension or bradycardia compared with those receiving propofol or dexmedetomidine (n = 156) (34.6% vs 63.5%; P < 0.001). Patients receiving ketamine also experienced smaller degree of hypotension observed by percent decrease in mean arterial pressure (25.3% [17.4] vs 33.8% [14.5]; P < 0.001) and absolute reduction in systolic blood pressure (26.5 [23.8] vs 42.0 [37.8] mm Hg; P < 0.001) and bradycardia (15.5 [24.3] vs 32.0 [23.0] reduction in beats per minute; P < 0.001). In multivariate logistic regression modeling, receipt of propofol or dexmedetomidine was the only independent predictor of a negative hemodynamic event (odds ratio [OR]: 3.3, 95% confidence interval [CI], 1.7 to 6.1; P < 0.001).Conclusion and RelevanceKetamine was associated with less clinically relevant hypotension or bradycardia when compared with propofol or dexmedetomidine, in addition to a smaller absolute decrease in hemodynamic parameters. The clinical significance of these findings requires further investigation.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-21T06:53:35Z
      DOI: 10.1177/10600280211051028
       
  • A Retrospective Analysis of Creatinine-Based Kidney Function With and
           Without Sex Assigned at Birth Among Transgender Adults

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      Authors: Sarah K. Fadich, Alin Kalayjian, Dina N. Greene, Lauren R. Cirrincione
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundClinicians use sex-based kidney function estimating equations, but the appropriate sex modifier for transgender adults undergoing hormone therapy (HT) is undetermined.ObjectivesCompare median estimated creatinine clearance (eCrCL; Cockcroft-Gault) and estimated glomerular filtration rates (eGFRs; Modification of Diet in Renal Disease [MDRD] and Chronic Kidney Disease Epidemiology Study [CKD-EPI]) before and during HT when estimated with and without sex assigned at birth.MethodsSingle-system retrospective cohort study of transgender adults (2007-2017) prescribed ≥90 days HT (index date = first order) and measured serum creatinine ≤6 months pre-index date (baseline) and ≤12 months post-index date. We grouped patients based on testosterone or estrogen treatment and compared eCrCL and eGFRs at baseline up to 6-12 months post-index date using equations based on sex assigned at birth (female or male modifier in testosterone or estrogen groups, respectively) or gender identity (male or female modifier in testosterone or estrogen groups, respectively). We used Wilcoxon signed-rank tests (Bonferroni correction) for all comparisons.ResultsIn total, 29 (median age 26 years, follow-up 259 days) and 41 patients (29 years, 250 days) were prescribed testosterone or estrogen, respectively. In the testosterone group, the maximum eCrCL and eGFR changes based on sex assigned at birth were −14%, P = 0.0181; −18%; P = 0.0009, respectively, and based on gender identity were +5%, P> 0.025 and +11%, P = 0.0094, respectively. In the estrogen group, eCrCL or eGFRs based on sex assigned at birth did not change from baseline but based on gender identity were −17%, P < 0.0001 and −26%, P < 0.0001, respectively.Conclusion and RelevanceFemale-based equations may underestimate kidney function in transgender adults undergoing testosterone or estrogen treatment. Prospective cohort studies are needed to confirm the clinical significance of these findings.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-20T10:44:47Z
      DOI: 10.1177/10600280211050120
       
  • Reply: A Review of Pharmacologic Neurostimulant Use During Rehabilitation
           and Recovery after Brain Injury

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      Authors: Sumie Kakehi, Danielle M. Tompkins
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-20T10:33:09Z
      DOI: 10.1177/10600280211052631
       
  • Direct Oral Anticoagulants Versus Preprohormone in Patients With Cirrhosis
           and the Risk of Gastrointestinal Bleeding

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      Authors: Karel Kostev, Sven Loosen, Christoph Roderburg, Christian Tanislav
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-16T11:15:20Z
      DOI: 10.1177/10600280211048008
       
  • Erroneous Computerized Interpretation of QTc and Changes to Patient Drug
           Therapy: Cautionary Example for Pharmacists

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      Authors: Doson Chua, Tanveer Brar
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-15T11:15:13Z
      DOI: 10.1177/10600280211049469
       
  • Sleep-Promotion Bundle Development, Implementation, and Evaluation in
           Critically Ill Adults: Roles for Pharmacists

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      Authors: Patricia R. Louzon, Mojdeh S. Heavner, Kyle Herod, Ting Ting Wu, John W. Devlin
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review evidence for intensive care unit (ICU) sleep improvement bundle use, identify preferred sleep bundle components and implementation strategies, and highlight the role for pharmacists in developing and evaluating bundle efforts.Data Sources:Multiple databases were searched from January 1, 1990, to September 1, 2021, using the MeSH terms sleep, intensive care or critical care, protocol or bundle to identify comparative studies evaluating ICU sleep bundle implementation.Study Selection and Data Extraction:Study screening, data extraction, and risk-of-bias evaluation were conducted in tandem. The ICU quality improvement literature and Institute for Healthcare Improvement bundle improvement guidance were also reviewed to identify recommended strategies for successful sleep bundle use.Data Synthesis:Nine studies (3 randomized, 1 quasi-experimental, 5 before-and-after) were identified. Bundle elements varied and were primarily focused on nonpharmacological interventions designed to be performed during either the day or night; only 2 studies included a medication-based strategy. Five studies were associated with reduced delirium; 2 studies were associated with improved total sleep time and 2 with improved patient-perceived sleep. Pharmacists were involved directly in 4 studies.Relevance to Patient Care and Clinical Practice:Sleep improvement bundles are recommended for use in all critically ill adults; specific bundle elements and ICU team member roles should be individualized at the institution/ICU level. Pharmacists can help lead bundle development efforts and routinely deliver key elements.Conclusions:Pharmacists can play an important role in the development and implementation of ICU sleep bundles. Further research regarding the relative benefit of individual bundle elements on relevant patient outcomes is needed.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-06T02:45:58Z
      DOI: 10.1177/10600280211048494
       
  • Prior Authorization Burden on the Use of LCP-Tacrolimus in Abdominal Solid
           Organ Transplant Recipients

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      Authors: David K. Choi, Shree Patel, Cassie Muran, Nehrin Khamo, Ruchik Patel, Nida Fayyaz, Patricia West-Thielke
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-06T02:45:45Z
      DOI: 10.1177/10600280211050641
       
  • Accelerated Approval of Aducanumab: Where Do We Stand Now'

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      Authors: Hedva Barenholtz Levy
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Aducanumab was approved by the Food and Drug Administration (FDA) in June 2021 to treat Alzheimer disease (AD). Its path to approval has been highly scrutinized, with many experts arguing that the FDA’s decision was premature. Accelerated approval was based on a surrogate end point, with evidence to support clinical effectiveness pending a postapproval trial by the drug company sponsor Biogen. As a result, the role of aducanumab in treating AD remains uncertain. A summary of key areas of controversy to guide informed decisions about use of this drug is provided, along with a timeline describing preapproval and postapproval events.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-01T11:26:07Z
      DOI: 10.1177/10600280211050405
       
  • Eptacog Beta for Bleeding Treatment and Prevention in Congenital
           Hemophilia A and B With Inhibitors: A Review of Clinical Data and
           Implications for Clinical Practice

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      Authors: Alana M. Ciolek, Justin Arnall, Donald C. Moore, Surabhi Palkimas, Julie Der-Nigoghossian, Kathryn Dane
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review the pharmacology, dosing and administration, safety, clinical efficacy, and role of eptacog beta in the treatment of congenital hemophilia with inhibitors.Data Sources:A literature search of PubMed (1966 to August 2021) was conducted using the keywords eptacog beta, recombinant FVII, and hemophilia.Study Selection and Data Extraction:All relevant published articles and prescribing information on eptacog beta for the treatment of congenital hemophilia with inhibitors were reviewed.Data Synthesis:Eptacog beta is a novel recombinant activated factor VII (rVIIa) product that demonstrated efficacy in controlling bleeding and associated pain in patients with hemophilia A or B with inhibitors. Eptacog beta has limited Food and Drug Administration–approved and off-label indications compared with other bypassing agents (BPAs; activated prothrombin complex concentrates [aPCC; eptacog alfa]). Eptacog beta costs less than eptacog alfa, but still more than aPCCs.Relevance to Patient Care and Clinical Practice:This review provides insight into the role of eptacog beta for treatment of congenital hemophilia with inhibitors and reviews important health system formulary considerations for available BPAs.Conclusions:Eptacog beta is more cost-effective than eptacog alfa and, as such, may become the preferred rVIIa formulary product. However, eptacog alfa availability remains necessary for the treatment of disorders where eptacog beta has limited data. aPCC should remain the first-line BPA for the treatment of bleeding in patients with inhibitors with no contraindications to use because of its equivocal efficacy and safety and in light of the magnitude of cost savings associated with this strategy.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-01T11:25:09Z
      DOI: 10.1177/10600280211049394
       
  • Risk of Gastrointestinal Bleeding on Treatment With Statin Alone or With
           Concomitant Administration of Warfarin: A Systematic Review and
           Meta-analysis of 5.3 Million Participants

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      Authors: Akshaya Srikanth Bhagavathula, Kota Vidyasaga, Eyob Alemayehu Gebreyohannes, Wubshet Tesfaye
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:This study aimed to comprehensively evaluate the risk of gastrointestinal bleeding (GIB) with statin monotherapy or with concomitant warfarin use.Data Sources:PubMed, Web of Science, and EMBASE (via Scopus) were searched for observational studies that reported the risk of GIB in adults on statin therapy or with concomitant warfarin use until August 28, 2021.Study Selection and Data Extraction:Observational studies evaluating the risk of GIB in adults (age>18 years) on statin medication or concomitant use with warfarin were included.Data Synthesis:In all, 14 studies with a total of 5 235 123 participants, reporting 48 677 GIB events (43 734 from statin users and 4943 from users of statin combined with warfarin), were included in the analyses. The pooled analysis revealed no difference in the risk of GIB with statin monotherapy (relative risk [RR]: 0.65; 95% CI: 0.42-1.02) or concomitant statin + warfarin use (RR: 0.97; 95% CI: 0.91-1.02). Prior use of statin was not associated with GIB risk (RR: 0.88; 95% CI: 0.63-1.22), whereas a shorter duration of statin use (
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-10-01T11:24:19Z
      DOI: 10.1177/10600280211049727
       
  • Inflammation Suppresses Patients’ Ability to Metabolize Cytochrome
           P450 Substrate Drugs

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      Authors: C. Michael White
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To assess the impact of inflammation on cytochrome P450 (CYP) drug metabolism in human subjects.Data Sources:A PubMed search was done from 1980 to July 2021 limited to human subjects and English language using a search strategy of (((phase I metabolism) OR (CYP) OR (cytochrome P450)) AND (inflammatory OR inflammation)).Study Selection and Data Extraction:Narrative review of human studies assessing the impact of inflammation or inflammatory suppression with biologic drugs on CYP drug metabolism were used.Data Synthesis:Patients with inflammatory conditions ranging from fungal, viral, or bacterial infections to noninfectious causes (critical illness, surgical procedure, cancer, or transplantation of stem cells or organs) have suppressed drug metabolism. Markers of inflammation such as C-reactive protein or α-1-acid glycoprotein are correlated with reduced clearance through CYP3A4, CYP1A2, and CYP2C19. Elevated interleukin-6 concentrations are also associated or correlated with reduced clearance for CYP3A4 and CYP2C-19 isoenzymes. There was insufficient information to properly assess CYP2D6.Relevance to Patient Care and Clinical Practice:Health professionals should appreciate that patients with acute or chronic inflammation from infectious or noninfectious causes could have suppressed drug metabolism through CYP3A4, CYP1A2, and CYP2C19. For narrow therapeutic index drugs, such as many of the drugs assessed in this review, that means more judicious drug monitoring to prevent adverse events.Conclusions:Like other types of drug-drug or drug-disease interactions, inflammation can alter the steady-state concentration of CYP metabolized drugs.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-30T12:45:14Z
      DOI: 10.1177/10600280211047864
       
  • Development of Patient Education Material for Proton Pump Inhibitor
           Deprescribing: A Mixed-Methods Study

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      Authors: Jérôme Nguyen-Soenen, Maud Jourdain, Jean-Pascal Fournier
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Proton pump inhibitor (PPI) deprescribing is recommended in case of inappropriate use. Patient education materials are key elements in the deprescribing process.Objective:The study objective was to develop patient education material for PPI deprescribing in primary care in France.Methods:This was a mixed-methods study involving (1) a literature review of the existing patient education materials on PPI deprescribing to identify key points to optimize the layout and content of the document; (2) development of a first version of the brochure by a pluri-professional steering group, following the national reference methodology of the French National Authority for Health (Haute Autorité de Santé) and iterative modifications of the patient brochure; (3) assessment of the content and understandability of the brochure by questionnaires followed by semistructured interviews with target patients; and (4) iterative brochure readability assessment with the Flesch reading ease tool.Results:The final patient education material is a double-sided A3 brochure—that is, 4 A4 pages. The first round of user testing by questionnaire (n = 14 patients) led to modifications to improve the document understandability, validated in the second round of user testing by questionnaire (n = 10 patients). The semistructured interviews (n = 10 patients) highlighted an adequate comprehension, whereas actionability required some minor modifications. The readability test score of the final education brochure was 59.4.Conclusion and Relevance:This patient education brochure for PPI deprescribing is targeted to patients in primary care. Its impact on PPI deprescribing will be assessed in a population-based pragmatic trial in primary care.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-23T10:53:26Z
      DOI: 10.1177/10600280211046630
       
  • Safety and Efficacy of Direct Oral Anticoagulants in Patients With
           Moderate to Severe Cirrhosis

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      Authors: Mildred Oldham, Surabhi Palkimas, Amanda Hedrick
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Direct oral anticoagulants (DOACs) remain mostly investigational in patients with moderate to severe hepatic cirrhosis, yet are often selected over traditional anticoagulants including warfarin and enoxaparin in this setting.Objective:To determine the safety and efficacy of DOACs in patients with moderate to severe hepatic cirrhosis as compared with traditional anticoagulation.Methods:This was a retrospective, single-center cohort study evaluating inpatients and outpatients who were prescribed a DOAC, warfarin, or enoxaparin for therapeutic anticoagulation with Child-Turcotte-Pugh (CTP) B or C status at the time that the prescription was written. Included patients were followed until first bleeding or thromboembolic event, or until discontinuation of anticoagulation therapy. Data were collected by manual chart review. The primary outcomes included both bleeding events and thromboembolic events in the DOAC population as compared with traditional anticoagulation.Results:A total of 101 patients were included in the study, 69 treated with DOAC therapy and 32 with traditional anticoagulation. Bleeding events occurred in 36% of patients in the DOAC group and 22% of patients in the traditional group (P = 0.149). In both groups, bleeds were most commonly gastrointestinal. Thromboembolic events occurred in 4% of the DOAC population and no patients in the traditional population (P = 0.55). No fatal bleeding or thromboembolic events occurred.Conclusion and Relevance:DOACs do not appear to be more harmful than traditional anticoagulation in patients with CTP B or C status. These results support the use of DOACs in patients with CTP B or C hepatic cirrhosis when considering safety, efficacy, and convenience.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-23T10:42:39Z
      DOI: 10.1177/10600280211047433
       
  • Call to Action: Addressing Social Determinants of Health in Pharmacy
           Practice

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      Authors: Julie Kalabalik-Hoganson, Ayse Elif Ozdener-Poyraz, Denise Rizzolo
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Social determinants of health (SDOH) are conditions in which individuals are born, live, work, learn, play, and age that affect health, risks, functioning, and outcomes. SDOH are recognized barriers to care, risk factors for certain diseases, and associated with poorer health outcomes. Screening for SDOH in physician practices and hospitals is reportedly low. The accessibility of pharmacists and established relationships with patients make pharmacy settings ideal for identifying and mitigating social needs. An evaluation of the impact of SDOH on health outcomes and opportunities for pharmacists to embed screening into practice is warranted.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-18T10:26:21Z
      DOI: 10.1177/10600280211040895
       
  • Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic
           Myeloid Leukemia

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      Authors: Andy H. Szeto, Tyler Bucci, Allison Deal, Anqi Zhu, Majd Ahmad, Amanda S. Cass, Margaret R. Sketch, Ryan Kemper, Joshua F. Zeidner, Matthew C. Foster, Benyam Muluneh, Daniel J. Crona
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs).Objective:To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs.Methods:Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations.Results:Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, respectively).Conclusion and Relevance:Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-18T10:26:01Z
      DOI: 10.1177/10600280211044160
       
  • Apixaban and Rivaroxaban Anti-Xa Level Monitoring Versus Standard
           Monitoring in Hospitalized Patients With Acute Kidney Injury

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      Authors: William Towers, Steffany N. Nguyen, Melanie C. Ruegger, Eric Salazar, Kevin R. Donahue
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Oral direct factor Xa inhibitors (FxaIs) are renally eliminated; thus, acute kidney injury (AKI) may increase the risk for drug accumulation and bleeding. There is minimal data describing the effects of AKI on FxaI anti-Xa levels or clinical outcomes.Objective:To compare anti-Xa level monitoring with standard monitoring in patients who experience AKI on apixaban or rivaroxaban.Methods:This retrospective study included patients admitted within a large hospital system from May 2016 to October 2020. Patients were included if they received apixaban or rivaroxaban prior to AKI. Patients were stratified into 1 of 2 groups: those with anti-Xa level monitoring or those who received standard monitoring. The primary outcome was major bleeding as defined by the International Society of Thrombosis and Haemostasis.Results:A total of 196 patients were included in the final analysis. Major bleeding occurred in 2 patients who received anti-Xa level monitoring, compared with 14 patients who received standard monitoring (2.1% vs 14%; P < 0.01). Variables identified as predictors of major bleeding included a documented history of liver disease (adjusted odds ratio = 3.17; 95% CI = 1.04-9.67; P = 0.04) and antiplatelet use (adjusted odds ratio = 4.18; 95% CI = 1.28-13.7; P = 0.02).Conclusion and Relevance:This is the first study to demonstrate that anti-Xa level monitoring was associated with a significant reduction in major bleeding compared with standard monitoring in patients with AKI who received apixaban or rivaroxaban. The optimal management of antithrombotic medications in patients with AKI and recent exposure to an FxaI requires further investigation.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-18T10:25:26Z
      DOI: 10.1177/10600280211046087
       
  • A Review of Selumetinib in the Treatment of Neurofibromatosis Type
           1–Related Plexiform Neurofibromas

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      Authors: Mary Kate Anderson, Meredith Johnson, Lauren Thornburg, Zachery Halford
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To evaluate the safety and efficacy of selumetinib, a novel MEK inhibitor, for the treatment of plexiform neurofibromas (PN) in patients with neurofibromatosis type 1 (NF1).Data Sources:An English-based literature search of PubMed, EMBASE, and ClinicalTrials.gov was conducted using the terms selumetinib AND neurofibromatosis from inception to August 1, 2021.Study Selection and Data Extraction:Relevant prescribing information, abstracts, and articles identified through the search were considered for inclusion in this review.Data Synthesis:The open-label, multicenter, single-arm, phase II SPRINT trial demonstrated clinically significant improvements in PN-related complications. Of 50 symptomatic patients, 68% experienced a partial response, with a median change in tumor volume of −27.9% from baseline. Estimated progression-free survival at 3 years was 84%. Additionally, clinically meaningful improvements were seen on patient- and parent-reported assessments evaluating pain, range of motion, disfigurement, and quality of life. Overall, the adverse effect profile for selumetinib appears mild and manageable.Relevance to Patient Care and Clinical Practice:Selumetinib is the first FDA-approved treatment for inoperable PN in patients with NF1, demonstrating that MEK inhibition is a promising therapeutic strategy. Studies are ongoing to assess the effect of selumetinib on other NF1-associated tumor types and to determine the optimal dosing schedule and treatment duration. Cost and treatment burden must be considered when selecting selumetinib therapy.Conclusion:Selumetinib exhibits impressive antitumor activity and sustained clinical benefit in patients lacking other viable treatment options. Further studies are warranted to determine the optimal age of initiation, treatment duration, and overall cost-effectiveness of selumetinib.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-18T10:24:55Z
      DOI: 10.1177/10600280211046298
       
  • A Qualitative Systematic Review of Facilitators of and Barriers to
           Community Pharmacists–Led Anticoagulation Management Service

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      Authors: Oluwaseun Egunsola, Joyce W. Li, Liza Mastikhina, Oluwasefunmi Akeju, Laura E. Dowsett, Fiona Clement
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To identify the facilitators of and barriers to the implementation of Community Pharmacists–Led Anticoagulation Management Services (CPAMS).Data Sources:MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL Register of Controlled Trials were searched from inception until August 20, 2021.Study Selection and Data Extraction:All abstracts proceeded to full-text review, which was completed by 2 reviewers. Data extraction was completed by a single reviewer and verified. Analysis was completed using best-fit framework synthesis.Data Synthesis:A total of 17 articles reporting on CPAMS from 6 jurisdictions were included: 2 Canadian provincial programs (Nova Scotia, Alberta), a national program (New Zealand), and 3 cities in the United Kingdom (Whittington and Brighton and Hove) and Australia (Sydney). Facilitators of CPAMS included convenience for patients, accessibility for patients, professional satisfaction for pharmacists, increased efficiency in anticoagulation management, improved outcomes, enhanced collaboration, and scalability. Barriers included perceived poor quality of care by patients, resistance by general practitioners, organizational limits, capping of the number of eligible patients, and cost.Relevance to Patient Care and Clinical Practice:The barriers and facilitators identified in this review will inform health policy makers on the implementation and improvement of CPAMS for patients and health care practitioners.Conclusion and Relevance:CPAMS has been implemented in 6 jurisdictions across 4 countries, with reported benefits and challenges. The programs were structurally similar in most jurisdictions, with minor variations in implementation. New anticoagulation management programs should consider adapting existing frameworks to local needs.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-11T03:00:12Z
      DOI: 10.1177/10600280211045075
       
  • A Critical Analysis of the Specific Pharmacist Interventions and Risk
           Assessments During the 12-Month TRANSAFE Rx Randomized Controlled Trial

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      Authors: Haley M. Gonzales, James N. Fleming, Mulugeta Gebregziabher, Maria Aurora Posadas Salas, John W. McGillicuddy, David J. Taber
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundMedication safety issues have detrimental implications on long-term outcomes in the high-risk kidney transplant (KTX) population. Medication errors, adverse drug events, and medication nonadherence are important and modifiable mechanisms of graft loss.ObjectiveTo describe the frequency and types of interventions made during a pharmacist-led, mobile health–based intervention in KTX recipients and the impact on patient risk levels.MethodsThis was a secondary analysis of data collected during a 12-month, parallel-arm, 1:1 randomized clinical controlled trial including 136 KTX recipients. Participants were randomized to receive either usual care or supplemental, pharmacist-driven medication therapy monitoring and management using a smartphone-enabled app integrated with telemonitoring of blood pressure and glucose (when applicable) and risk-based televisits. The primary outcome was pharmacist intervention type. Secondary outcomes included frequency of interventions and changes in risk levels.ResultsA total of 68 patients were randomized to the intervention and included in this analysis. The mean age at baseline was 50.2 years; 51.5% of participants were male, and 58.8% were black. Primary pharmacist intervention types were medication reconciliation and patient education, followed by medication changes. Medication reconciliation remained high throughout the study period, whereas education and medication changes trended downward. From baseline to month 12, we observed an approximately 15% decrease in high-risk patients and a corresponding 15% increase in medium- or low-risk patients.Conclusion and RelevanceA pharmacist-led mHealth intervention may enhance opportunities for pharmacological and nonpharmacological interventions and mitigate risk levels in KTX recipients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-09T05:10:26Z
      DOI: 10.1177/10600280211044792
       
  • Liposomal Bupivacaine Versus Immediate-Release Bupivacaine for
           Postoperative Pain Control

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      Authors: Atul Dilawri, Marcia Wyman, Sneha Shah
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundLiposomal bupivacaine (LB) is increasingly being used for postoperative pain control, but there are conflicting efficacy data when compared with immediate-release bupivacaine (IRB).ObjectiveTo evaluate the comparative efficacies of LB and IRB for postoperative pain control in order to assess the formulary status of LB at our institution.MethodsA single-center, retrospective, institutional review board–approved, noninferiority matched cohort study at a tertiary care academic medical center. Adult surgical patients admitted for>24 hours who received LB or IRB were included. The primary outcome was total opioid consumption within 24 hours postoperatively. Secondary outcomes included total opioid consumption within 72 hours postoperatively, nonopioid analgesic use within 24 and 72 hours postoperatively, time to rescue analgesic use, and postoperative length of stay (LOS).ResultsA total of 326 patients were included in the matched cohort. Median 24-hour opioid consumption was significantly lower in the IRB group compared with the LB group (81 mg [30, 153] vs 103 mg [46, 241]; P = 0.01). Patients receiving IRB compared with LB also had a decrease in total opioid consumption 72 hours postoperatively (110 mg [45, 258] vs 165 mg [68, 402]; P = 0.005) and shorter postoperative LOS (2.8 days [1.7, 4] vs 3.3 days [2, 5.1]; P < 0.001). There was no difference in time to rescue analgesic use.Conclusion and RelevanceAcross a variety of surgical procedures, administration of IRB compared with LB was associated with a reduction in total opioid consumption within 24 and 72 hours postoperatively and shorter LOS in adult surgical patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-09T05:07:17Z
      DOI: 10.1177/10600280211043554
       
  • Comment: The Safety of Continuous Infusion Propofol in Mechanically
           Ventilated Adults With Coronavirus Disease 2019

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      Authors: Ju-Tae Sohn
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-09T05:04:12Z
      DOI: 10.1177/10600280211043505
       
  • Development and Implementation of a Multicomponent Protocol to Promote
           Sleep and Reduce Delirium in a Medical Intensive Care Unit

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      Authors: Adrienne Darby, Kalynn Northam, C. Adrian Austin, Lydia Chang, Stacy Campbell-Bright
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Evidence suggests that poor sleep increases risk of delirium. Because delirium is associated with poor outcomes, institutions have developed protocols to improve sleep in critically ill patients.Objective:To assess the impact of implementing a multicomponent sleep protocol.Methods:In this prospective, preimplementation and postimplementation evaluation, adult patients admitted to the medical intensive care unit (ICU) over 42 days were included. Outcomes evaluated included median delirium-free days, median Richards-Campbell Sleep Questionnaire (RCSQ) score, median optimal sleep nights, duration of mechanical ventilation (MV), ICU and hospital length of stay (LOS), and in-hospital mortality.Results:The preimplementation group included 78 patients and postimplementation group, 84 patients. There was no difference in median delirium-free days (1 day [interquartile range, IQR, = 0-2.5] vs 1 day [IQR = 0-2]; P = 0.48), median RCSQ score (59.4 [IQR = 43.2-71.6] vs 61.2 [IQR = 49.9-75.5]; P = 0.20), median optimal sleep nights (1 night [IQR = 0-2] vs 1 night [IQR = 0-2]; P = 0.95), and in-hospital mortality (16.7% vs 17.9%, P = 1.00). Duration of MV (8 days [IQR = 4-10] vs 4 days [IQR = 2-7]; P = 0.03) and hospital LOS (13 days [IQR = 7-22.3] vs 8 days [IQR = 6-17]; P = 0.05) were shorter in the postimplementation group, but both were similar between groups after adjusting for age and severity of illness.Conclusions and Relevance:This report demonstrates that implementation of a multicomponent sleep protocol in everyday ICU care is feasible, but limitations exist when evaluating impact on measurable outcomes. Additional evaluations are needed to identify the most meaningful interventions and best practices for quantifying impact on patient outcomes.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-07T09:28:45Z
      DOI: 10.1177/10600280211043278
       
  • Reply: The Safety of Continuous Infusion Propofol in Mechanically
           Ventilated Adults With Coronavirus Disease 2019

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      Authors: Corey J. Witenko, Audrey J. Littlefield, Sajjad Abedian, Anjile An, Philip S. Barie, Karen Berger
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-06T06:22:12Z
      DOI: 10.1177/10600280211043188
       
  • Evaluation of Inhaled Alprostadil in Hospitalized Adult Patients

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      Authors: Hangil Seo, Chelsea N. Lopez, Luma Succar, Kevin R. Donahue
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Intermittent inhaled alprostadil (iPGE1) may be a viable alternative to inhaled nitric oxide or epoprostenol for management of right ventricular failure, pulmonary hypertension (pHTN) or acute respiratory distress syndrome (ARDS). However, limited evidence exists regarding iPGE1 use in adults, ideal dosing strategies, or optimal use cases.ObjectiveTo describe the clinical characteristics of patients receiving iPGE1 and identify specific sub-populations warranting further research.MethodsThis was a single-center, retrospective, descriptive analysis of inpatients who received at least one dose of iPGE1. The primary outcome was to describe patient characteristics and alprostadil dosing strategies. Secondary outcomes included changes in respiratory support requirements, hemodynamics, and inotropic/vasoactive use. Outcomes were stratified and compared based on primary therapeutic indication (cardiac or pulmonary).ResultsFifty-four patients received iPGE1 40 (75%) for pulmonary (pHTN or ARDS) and 14 (25%) for cardiac indications. There was no difference between indications in the number of patients de-escalated from level of respiratory (53% vs 57%, P = 0.76), inotropic (70% vs 57%, P = 0.39), or vasopressor support (78% vs 57%, P = 0.17). Furthermore, there was no significant improvement in cardiopulmonary parameters at multiple time intervals after iPGE1 initiation.Conclusion and RelevanceThis is the largest study to date on the use of intermittent iPGE1 in adults. Alprostadil was safely utilized in novel populations; however, efficacy as evaluated by clinical or surrogate endpoints could not be demonstrated and further investigation is needed to determine its potential and optimal place in therapy.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-06T06:19:52Z
      DOI: 10.1177/10600280211042675
       
  • Evaluation of the Impact of Prior-to-Admission Sleep Aid Prescribing
           Practices on Sleep and Delirium in the Intensive Care Unit

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      Authors: Melissa Chudow, Vittorio Paradiso, Nicole Silva, Jillian Collette
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Sleep disruptions in the intensive care unit (ICU) may lead to complications such as delirium. There is limited evidence addressing how sleep aid use before and during ICU admission affects outcomes.Objective:The purpose of this study is to evaluate the impact of prior-to-admission sleep aid prescribing practices in the ICU on delirium and sleep outcomes.Methods:A retrospective review was conducted of adult patients admitted to any ICU from January to June 2018 receiving a sleep aid prior to admission. Patients were categorized based on sleep aid continuation, discontinuation, or alteration during the ICU admission. The primary end point was the incidence of delirium. Secondary end points included the incidence of sleep-wake cycle disturbances, delirium scores, and ICU length of stay.Results:A total of 291 patients were included with 109 in the continued group, 121 in the discontinued group, and 61 in the altered group. There was a similar incidence of delirium at 24 hours (P = 0.71), 48 hours (P = 0.60), 72 hours (P = 0.25), and 5 days (P = 0.48) after ICU admission. There was also no statistical difference in sleep-wake cycle disturbances or delirium scores at any time point. ICU length of stay was similar between the groups.Conclusion and Relevance:The incidence of delirium and sleep-wake cycle disturbances was not affected by differences in prior-to-admission sleep aid prescribing patterns during ICU admission.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-06T06:15:07Z
      DOI: 10.1177/10600280211042632
       
  • Hypertriglyceridemia in Critically Ill Patients With SARS-CoV-2 Infection

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      Authors: Wasim S. El Nekidy, Abdullah Shatnawei, Manal M. Abdelsalam, Mariam Hassan, Ruba Z. Dajani, Nouran Salem, Terrence J. Lee St. John, Nadeem Rahman, Fadi Hamed, Jihad Mallat
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundPatients with SARS-CoV-2 infection could develop severe disease requiring critical care admission. Case reports indicated high incidence of hypertriglyceridemia (HTG) in critically ill patients infected with SARS-CoV-2, which might be related to the drugs.ObjectiveWe sought to determine the risk factors associated with HTG in this population and to investigate the relationship between HTG and lipase.MethodsA retrospective observational study was conducted at our hospital between March 1 and June 30, 2020. Patients were included if they were ≥18 years old, admitted to the intensive care unit (ICU), tested positive for SARS-CoV-2, and had triglycerides (TG) checked during their hospital stay.ResultsOf the 111 critically ill patients, 103 patients were included. Males comprised 88.3% of the sample. The median TG at baseline was 197.4 (IQR: 139.8-283) mg/dL. The lipase median level at baseline was 23.00 (IQR: 0.00-69.50) IU/L. The results of the mixed-effects logistic regression analysis indicated that patient-level variables, favipiravir use, blood glucose level, and propofol use were significantly associated with HTG. There was no relationship between lipase and TG levels over time. Furthermore, TG concentrations over time showed a similar trend to inflammatory markers.Conclusion and RelevanceThe incidence of clinically significant HTG was high and was associated with propofol and favipiravir use. HTG might reflect the high inflammatory state in these patients. Clinicians should look at the full picture before changing therapies based only on HTG. Our findings need to be replicated in a larger prospective study.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-02T05:00:47Z
      DOI: 10.1177/10600280211038302
       
  • Direct Oral Anticoagulants Versus Warfarin for Treatment of Thrombosis or
           Atrial Fibrillation in Patients With Cirrhosis: A Retrospective Cohort
           Study

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      Authors: Eric M. Coons, Britta A. Staubes, Ashley L. Casey, Stephanie A. Elagizi-Youssef, Alaa E. Mohammed, Nikhil Sharma, Elle R. Kline
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundEvidence for direct oral anticoagulants (DOACs) in patients with cirrhosis is limited. Few patients with Child-Turcotte-Pugh (CTP) class B and C cirrhosis have been studied.ObjectiveTo compare major bleeding rates in patients with cirrhosis receiving a DOAC versus warfarin.MethodsA retrospective cohort study was conducted in adults with cirrhosis receiving a DOAC versus warfarin for venous thromboembolism, portal-vein thrombosis, or atrial fibrillation. The primary outcome was the rate of major bleeding. Secondary outcomes included time to major bleeding, clinically relevant nonmajor bleeding, all bleeding, gastrointestinal bleeding, intracranial bleeding, and new thromboembolic events. The study was approved by the Ochsner Health System Institutional Review Board.ResultsA total of 44 patients receiving a DOAC and 41 patients receiving warfarin were included. Major bleeding occurred in 4 patients receiving a DOAC and 6 patients receiving warfarin (9.1% vs 14.6%; P = 0.881). Rates of major bleeding were similar in 24 DOAC and 17 warfarin patients with CTP Class B (4.2% vs 17.6%; P = 0.37) and 8 DOAC and 9 warfarin patients with CTP Class C (37.5% vs 11.1%; P = 0.41) cirrhosis. Secondary bleeding and efficacy outcomes were similar between cohorts. The study was limited by a small sample size.Conclusion and RelevanceTreatment with DOACs in patients with cirrhosis was associated with a similar rate of major bleeding compared with warfarin. Inclusion of CTP class C patients in future studies remains valuable to evaluate safety and efficacy of DOACs in this population.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-09-02T04:59:32Z
      DOI: 10.1177/10600280211025050
       
  • Effectiveness and Safety of Twice- Versus Thrice-Daily Subcutaneous
           Heparin for Venous Thromboembolism Prophylaxis at a Large Academic Medical
           Center

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      Authors: Eryne E. Wiethorn, Sarah Harrison, Erin R. Weeda, Carolyn Magee Bell
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundDosing variation of subcutaneous unfractionated heparin (UFH) exist for venous thromboembolism prophylaxis (VTEP).ObjectiveThe purpose of this study was to compare the safety and effectiveness of thrice-daily (TID) versus twice-daily (BID) administration of UFH during a heparin shortage for VTEP.MethodsA single-center retrospective analysis was conducted in patients with orders for BID subcutaneous UFH during a heparin shortage from September 1, 2019, to February 4, 2020. These patients were matched to patients with TID subcutaneous UFH orders from January 1, 2019, to May 31, 2019. The primary outcome was the incidence of deep-vein thrombosis or pulmonary embolism confirmed by imaging during hospitalization. The secondary outcome was the incidence of major or clinically relevant nonmajor bleeding events as defined by International Society on Thrombosis and Haemostasis (ISTH) definitions.ResultsA total of 277 patients with orders for BID UFH and meeting inclusion criteria were evaluated and matched to patients who received TID UFH. After the exclusion criteria were implemented, 510 patients remained in the TID group. The primary outcome occurred in 4% of patients in the BID group and 3% in the TID group (P = 0.645). Major bleeding or clinically relevant nonmajor bleeding events occurred in 10% of patients in the BID group and 8% in the TID group (P = 0.310).Conclusion and RelevanceThere was no difference in effectiveness or safety of TID versus BID subcutaneous UFH for VTEP. During a heparin shortage, transitioning patients to BID UFH for VTEP to conserve supply may be considered.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-30T05:30:08Z
      DOI: 10.1177/10600280211041380
       
  • Impact of Pharmacist Activities in Patients With Depression: A Systematic
           Review and Meta-analysis of Randomized Controlled Trials

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      Authors: Waranee Bunchuailua, Nathapol Samprasit, Surachai Kotirum, Nattiya Kapol
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundDepression is a substantial health burden. Pharmacist activities may help improve health outcomes of patients with depression when comparing to current practice with no pharmacist-involved intervention.ObjectiveTo systematically review and analyze randomized controlled trials assessing the impact of pharmacist services on patients with depression compared to usual care using a meta-analysis approachMethodsFour international and 3 domestic electronic databases were systematically searched. Data from database inception to December 2019 were included. Studies were selected using predefined inclusion criteria, and quality was assessed using the risk-of-bias criteria. Pooled estimation was analyzed to report the relative risk (RR) and standard mean difference (SMD). The meta-analysis used the random-effect model when heterogeneity was observed between studies.ResultsA total of 12 eligible studies with 2133 patients with depression were included in the analysis. The relevant pharmacist interventions included medication therapy management, adherence counseling, and educational advice about depression and antidepressants. Pooled data in the meta-analysis showed a significantly increased number of patients with good adherence (RR = 1.39; 95% CI = 1.11 to 1.75) and improved medication adherence score (SMD = 0.32; 95% CI = 0.07 to 0.56) associated with pharmacist activities compared to usual care. No significant differences were detected in clinical rating scales (SMD = −0.03; 95% CI = −0.16 to 0.10) and quality of life (SMD = 0.10; 95% CI = −0.04 to 0.25)Conclusion and RelevanceThis review suggests that the role of pharmacists in patients with depression has a positive impact on medication adherence.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-30T05:28:43Z
      DOI: 10.1177/10600280211041274
       
  • A Review of Direct Oral Anticoagulants in Patients With Stage 5 or
           End-Stage Kidney Disease

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      Authors: Jessica A. Starr, Nathan A. Pinner, Melanie Mannis, Mary Katherine Stuart
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To evaluate the role of oral anticoagulation in patients with stage 5 chronic kidney disease (CKD-5) or end-stage kidney disease (ESKD).Data Sources:A literature search of PubMed (January 2000 to July 1, 2021), the Cochrane Library, and Google Scholar databases (through April 1, 2021) was performed with keywords DOAC (direct-acting oral anticoagulant) OR NOAC or dabigatran OR rivaroxaban OR apixaban OR edoxaban AND end-stage kidney disease combined with atrial fibrillation (AF) or venous thromboembolism (VTE) OR pulmonary embolism OR deep-vein thrombosis.Study Selection and Data Extraction:Case-control, cohort, and randomized controlled trials comparing DOACs to an active control for AF or VTE in patients with CKD-5 or ESKD and reporting outcomes of stroke, recurrent thromboembolism, or major bleeding were included.Data Synthesis:Nine studies were included. Efficacy data supporting routine use of warfarin or DOACs in CKD-5 or ESKD are limited. Rivaroxaban and apixaban may provide enhanced safety compared to warfarin in patients with AF. Data for VTE are limited to 1 retrospective study.Relevance to Patient Care and Clinical Practice:Because of the paucity of rigorous, prospective studies in CKD-5 or ESKD, OACs should not be broadly used in this population. It is clear that data regarding efficacy of DOACs cannot be reliably and safely extrapolated from the non-ESKD population. Therefore, use of OACs in this population should be individualized.Conclusions:If OACs for stroke prevention with AF are deemed necessary, apixaban or rivaroxaban can be considered. DOACs cannot currently be recommended over warfarin in patients with CKD-5 or ESKD and VTE.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-30T05:27:23Z
      DOI: 10.1177/10600280211040093
       
  • MenQuadfi (MenACWY-TT): A New Vaccine for Meningococcal Serogroups ACWY

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      Authors: Jessica Huston, Kevin Galicia, Eric F. Egelund
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveThis article reviews data encompassing the pharmacology, efficacy, and safety of MenACWY-TT (MenQuadfi), a conjugate vaccine to prevent meningococcal disease from serogroups A, C, W, Y.Data SourcesA literature review was conducted in PubMed, MEDLINE, and ClinicalTrials.gov from inception up to July 2021, using the search terms MenQuadfi, meningococcal ACWY vaccine, MCV4, and menacwy. Articles from reference lists were included to identify potential relevant literature.Study Selection and Data ExtractionData were limited to randomized phase II and III clinical studies published in the English language, evaluating the efficacy and safety of MenACWY-TT. Animal studies and studies not utilizing MenACWY-TT were excluded.Data SynthesisOne phase II and 4 phase III randomized clinical studies, enrolling approximately 7700 participants, aged 2 years to 97 years old found that MenACWY-TT was noninferior when compared to established MenACWY vaccines, as measured by surrogate immunogenicity end points. In studies evaluating primary dose vaccination, conducted in those aged 2 to 97 years of age, the difference in seroresponse rates, reported by the lower bound of the 95% CI, was (A) 1.1% to 14.8%, (C) 21% to 42.2%, (Y) 7.7% to 24.6%, and (W) 8.9% to 22.5%.Relevance to Patient Care and Clinical PracticeDespite the low incidence of meningococcal disease in the United States, meningococcal disease causes significant morbidity and mortality if not prevented.ConclusionMenACWY-TT is noninferior to currently approved quadrivalent meningococcal vaccines and shows similar immunogenicity and safety as both an initial vaccine for prevention as well as a booster dose.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-30T05:26:28Z
      DOI: 10.1177/10600280211039873
       
  • Outcome Benefits Seen With 1 Year of Optimized Sacubitril/Valsartan for
           the Treatment of Systolic Heart Failure Managed by Pharmacists in a
           Cardiology Practice

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      Authors: Lindsay E. Davis, Elizabeth K. Pogge
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Pharmacists’ care in heart failure (HF) management has been shown to better clinical outcomes, including use of guideline-directed medical therapy and hospital readmission, although the impact observed has varied among studies.Objective:To investigate the rates of all-cause hospitalization and hospitalization from HF (hHF) and changes in surrogate markers (left-ventricular ejection fraction, New York Heart Association Functional Classification [NYHA FC], diuretic requirements) for patients with HF with reduced ejection fraction (HFrEF) on angiotensin receptor-neprilysin inhibitor (ARNi) therapy optimized within a pharmacist clinic.Methods:Retrospective chart review of patients with HFrEF on sacubitril/valsartan from July 7, 2015, through January 1, 2018.Results:For the primary outcome analysis, 70 patients with pre/post hospitalization data had a reduction in the rate of all-cause hospitalization from 45.7% in the 12 months prior to ARNi therapy initiation to 24.3% during the first year on optimized ARNi therapy (P = 0.004). The rate of hHF reduced from 24.3% to 8.6% (P = 0.003). For the secondary outcome analyses at the 6-month assessment point, which included 104 patients, ejection fraction improved from 26% to 34% (P < 0.001), NYHA FC improved or remained unchanged in 86.6% of patients, and weekly loop diuretic dosing requirements were significantly reduced.Conclusion and Relevance:Real-world use of sacubitril/valsartan optimized within a pharmacist clinic was associated with reduced prevalence of all-cause and hHF during the first year of ARNi therapy. This study corroborates pharmacist involvement in HF management, which could be used to support further research and expanded pharmacist services.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-28T10:25:07Z
      DOI: 10.1177/10600280211036149
       
  • Rilonacept: A Newly Approved Treatment for Recurrent Pericarditis

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      Authors: Nicholas C. Schwier
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo review the pharmacology, efficacy, and safety of rilonacept for the prevention and treatment of recurrent pericarditis (RP).Data SourcesA MEDLINE search was conducted between January 2006 and April 2021 using the following terms: rilonacept, pharmacology, pericarditis, recurrent pericarditis, interleukin (IL) antagonist, and pharmacology; prescribing information was also used.Study Selection and Data ExtractionEnglish-language studies assessing pharmacology, efficacy, and safety of IL antagonists were reviewed.Data SynthesisRilonacept traps IL-1α and IL-1β. In the Phase III trial, rilonacept was associated with a lower risk of recurrence, more persistent clinical response, and higher amount of days with no or minimal pericarditis symptoms, compared with placebo. The median time to pain response was 5 days, and median time to normalization of C-reactive protein was 7 days with rilonacept. All patients receiving rilonacept during the run-in period were able to be weaned off of standard background therapy, leading to transition to rilonacept monotherapy. The most common adverse effects were upper respiratory tract infections and injection site reactions.Relevance to Patient Care and Clinical PracticeRilonacept may be used for the prevention and treatment of multiple recurrences in patients receiving background therapy for RP, and reduction in risk of recurrence in adults and adolescents ≥12 years with elevated C-reactive protein. Rilonacept may be considered to wean patients from standard background therapy.ConclusionRilonacept is a safe, once weekly, subcutaneously administered IL-1 “trap,” indicated for the treatment of RP, and reduction in risk of recurrent pericarditis in adults and children ≥12 years of age.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-28T10:15:32Z
      DOI: 10.1177/10600280211036499
       
  • Primary Care Pharmacist Practice Models Shape the Comprehensive Medication
           Management Process

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      Authors: Mary Mulrooney, Marie Smith
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Pharmacists are well positioned to collaborate with primary care providers (PCPs) to conduct comprehensive medication management (CMM). However, depending on organizational needs and pharmacist staffing resources, different pharmacist practice models have been implemented. In this commentary, we (1) describe 2 common pharmacist practice models in primary care settings, (2) explain variations in the CMM process based on 2 practice models, and (3) outline outcomes and implications of this expanded CMM process. By tailoring the CMM process to their practice model, pharmacists can follow consistent delivery of CMM services to create a common understanding among patients, PCPs, and other care team members.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-25T12:50:15Z
      DOI: 10.1177/10600280211042031
       
  • Vericiguat: A Novel Oral Soluble Guanylate Cyclase Stimulator for the
           Treatment of Heart Failure

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      Authors: Nicole Campbell, Julie Kalabalik-Hoganson, Kathleen Frey
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo review the efficacy and safety of vericiguat indicated to reduce the risk of cardiovascular death and heart failure (HF) hospitalization following hospitalization or need for outpatient intravenous diuretics in adult patients with chronic symptomatic HF and ejection fraction (EF) less than 45%.Data SourcesA literature search through MEDLINE with search terms MK1242, BAY 1021189, and vericiguat was conducted. Product labeling and English-language studies assessing pharmacokinetics, pharmacodynamics, efficacy, or safety of vericiguat were included.Study Selection and Data ExtractionPreclinical and clinical studies describing the efficacy and safety of vericiguat were included.Data SynthesisThe phase 3 VICTORIA clinical trial demonstrated a lower composite primary outcome of death from cardiovascular causes or first hospitalization in the vericiguat group compared to placebo. Total hospitalizations for HF in the vericiguat group were significantly less compared to placebo. The composite secondary outcome of death from any cause or first HF hospitalization was significantly less in the vericiguat group.Relevance to Patient Care and Clinical PracticeThe addition of vericiguat offers a new treatment option for those in whom rehospitalization or recurrent outpatient intravenous diuretic treatment is a concern. Given high rates of nonadherence in HF patients, vericiguat represents an additional treatment option, especially for patients who do not tolerate available HF therapies.ConclusionVericiguat is a novel soluble guanylate cyclase stimulator that is safe and effective for reducing the risk of cardiovascular death and HF hospitalization in adults with symptomatic chronic HF and reduced EF.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-25T12:49:20Z
      DOI: 10.1177/10600280211041384
       
  • Proton Pump Inhibitors and the Risk of Community-Acquired Pneumonia: An
           Updated Meta-analysis

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      Authors: Xuejiao Xun, Qifan Yin, Yuhao Fu, Xueru He, Zhanjun Dong
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Some studies suggested an increased risk of community-acquired pneumonia (CAP) among proton pump inhibitors (PPI) users. However, the published evidence is inadequate to define the association between PPI use and the risk of CAP.Objective:The aims of our meta-analysis were to systematically assess the association between the risk of CAP and PPI use in adults to reduce the adverse effects of PPI and ensure the safety of medication for patients.Methods:A comprehensive literature search was conducted, published between January 1, 2004, and February 1, 2021. The primary outcome was the incidence of CAP. This meta-analysis was performed using odds ratios (ORs) with 95% CIs as effective measures; 13 studies including 2 098 804 patients were enrolled in our meta-analysis.Results:Our study revealed that the incidence of CAP was higher in PPI users than non -PPI users [OR = 1.37 (95% CI = 1.22–1.53)], especially for PPI duration < 30 days [OR = 1.49 (95% CI = 1.34–1.66)]. Compared with non-PPI use, PPI use increased the incidence of CAP in the stroke disease population [OR = 1.52 (95% CI = 1.33–1.75)], but not in the liver disease population [OR = 1.13 (95% CI = 0.98–1.30)].Conclusions and Relevance:Using PPI could increase the risk of CAP when compared to not using PPI. PPI use increased the incidence of CAP in patients with stroke. Clinicians and clinical pharmacists should weigh the benefits before medication and strictly control the indication of the prescription, so as to reduce adverse reactions.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-24T04:39:37Z
      DOI: 10.1177/10600280211039240
       
  • Ozanimod: A First-in-Class Sphingosine 1-Phosphate Receptor Modulator for
           the Treatment of Ulcerative Colitis

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      Authors: David Choi, Alyssa P. Stewart, Shubha Bhat
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo review the pharmacological and clinical profile of ozanimod in the treatment of ulcerative colitis (UC).Data SourcesA PubMed search was conducted from inception to July 2021 using the keywords ozanimod, ulcerative colitis, and sphingosine 1-phosphate receptor modulator. Information was also extracted from published abstracts and the package insert.Study Selection and Data ExtractionPhase 2 and 3 studies and relevant literature on ozanimod pharmacological and clinical profiles were reviewed.Data SynthesisOzanimod approval was based on True North, a phase 3 trial evaluating ozanimod’s efficacy and safety in the treatment of moderate to severe UC. Compared with placebo, ozanimod led to clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. Additionally, for secondary end points of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing, ozanimod performed significantly better than placebo. Common adverse events included infections, headaches, hypertension, bradycardia, and liver enzyme elevations.Relevance to Patient Care and Clinical PracticeOzanimod is the first sphingosine 1-phosphate modulator to be approved for UC and is administered orally. Its efficacy profile is comparable with other UC medications. However, its safety profile is unique, requiring extensive assessments prior to initiation of and during treatment. Thus, it is unclear how ozanimod will be positioned in UC treatment.ConclusionOzanimod is another option in the growing arsenal of UC treatment. Although it offers a novel mechanism of action and is administered orally, there are important safety, dosing, and pharmacokinetic factors to consider prior to initiation and use.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-23T06:21:44Z
      DOI: 10.1177/10600280211041907
       
  • Heparin Monitoring with an Anti-Xa Protocol Compared to Activated Clotting
           Time in Patients on Temporary Mechanical Circulatory Support

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      Authors: Joel T. Feih, Kirsten E. Wallskog, Joseph R. G. Rinka, Janelle J. Juul, Lisa Rein, Nunzio Gaglianello, Lisa M. Baumann Kreuziger, David L. Joyce, Justin N. Tawil
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Temporary mechanical circulatory support (tMCS) devices are used for patients with severe cardiac or respiratory failure; however, these patients are at high risk for clotting and bleeding. The best method to monitor heparin in these patients has not been established.Objective:To determine the risks for bleeding and clotting while monitoring heparin with either anti-Xa or activated clotting time (ACT) in tMCS patients.Methods:A retrospective cohort study was conducted on tMCS patients who received heparin adjusted according to an anti-Xa or ACT protocol. The primary outcome was incidence of major bleeding. Pertinent secondary outcomes were individual components of the primary outcome, clotting events, and time to therapeutic range.Results:There were 103 patients included in the study: 53 in the ACT group and 50 in the anti-Xa group. Overall, there were 30 (56.6%) patients with major bleeding in the ACT group, compared with 16 (32%) patients in the anti-Xa group (P = 0.017). An anti-Xa–based protocol was associated with a decreased hazard of major bleeding (hazard ratio = 0.388 [0.215-0.701]; P = 0.002) in the univariate analysis. In the multivariable analysis, an anti-Xa protocol remained associated with a significantly lower hazard of bleeding. Findings were similar when broken down into more discrete subgroups of the entire cohort, extracorporeal membrane oxygenation life support (ECMO), and non-ECMO groups.Conclusion and Relevance:Anti-Xa monitoring was associated with a lower hazard of bleeding during tMCS compared to an ACT-based protocol. Further studies should evaluate if anti-Xa monitoring should be preferentially used in tMCS.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-23T06:19:54Z
      DOI: 10.1177/10600280211039582
       
  • Incidence of Heparin-Induced Thrombocytopenia in Patients With Newly
           Implanted Mechanical Circulatory Support Devices

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      Authors: Long To, Dana Attar, Brittany Lines, Melissa McCarty, Hassan Nemeh, Ileana Lopez-Plaza, Zachary Smith, Victor Coba, Jona Lekura
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Heparin exposure and device-related thrombocytopenia complicate the diagnosis of heparin-induced thrombocytopenia (HIT) in patients receiving mechanical circulatory support (MCS). To improve anticoagulation management for patients with newly implanted MCS devices, incidence of confirmed HIT needs to be further characterized.Objectives:The purpose of this study is to describe the incidence of HIT and clinical utility of the 4Ts score in patients with newly implanted MCS devices.Methods:This is a retrospective analysis of MCS patients receiving unfractionated heparin from 2014 to 2017. The primary end point was incidence of laboratory-confirmed HIT. Strong positive, likely positive, low probability, and negative HIT categories were established based on heparin-induced platelet antibody (HIPA) and serotonin release assay (SRA). Secondary end points include characterization of platelet trends, argatroban use, incidence of HIT among each of the MCS devices, and utility of 4Ts score.Results:A total of 342 patient encounters met inclusion criteria, of which 68 HIPA tests and 25 SRAs were ordered. The incidence of HIT was 0.88% (3/342) and 4.4% (3/68) in patients with suspected HIT. Of the 68 HIPA tests, 3 (4.4%) were considered strong positive and 3 of the 25 SRAs were positive. Median 4Ts score was 4 [2.5-4] and optical density 0.19 [0.11-0.54]. The positive predictive value for the 4Ts score was 0.15 (CI = 0.03-0.46) and negative predictive value, 0.93 (CI = 0.82-0.98).Conclusion and Relevance:HIT occurs infrequently with newly implanted MCS devices. The 4Ts score appears to have a high negative predictive value for ruling out HIT.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-12T11:35:47Z
      DOI: 10.1177/10600280211038705
       
  • Dolutegravir-Based Dual Therapies in HIV Pretreated Patients: A Real-Life
           Study in Madrid

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      Authors: Miguel Ángel Amor-García, Carmen Guadalupe Rodríguez-González, Esther Chamorro-de-Vega, Ana Herranz-Alonso, María Sanjurjo-Sáez
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Few studies describe the use of dolutegravir (DTG)-based dual therapies under routine clinical practice.Objectives:To report real-life data on the use of DTG-based dual therapies in treatment-experienced patients.Methods:This was an observational, retrospective study. It included all treatment-experienced HIV patients starting a DTG-based dual therapy from 2014 to 2018. The primary end point was to identify the incidence and reasons for the switch. The secondary end points were to assess the effectiveness, safety, adherence, and costs after 48 weeks of treatment (W48).Results:The incidence of the switch to a DTG-based dual therapy increased from 1.6 patients per 1000 patient-years in 2014 to 38.6 in 2018. A total of 241 patients initiated this therapy: 113 (46.9%) patients started DTG plus rilpivirine (RPV), 72 (29.9%), DTG plus lamivudine (3TC), and 68 (28.2%), DTG plus boosted-darunavir (b-DRV). A total of 170 patients completed W48 of follow-up. By intention-to-treat analysis, 89.3% of virologically suppressed (VS) patients (94.3% with DTG plus b-DRV, 91.3% with DTG plus 3TC, and 87.2% with DTG plus RPV) and 56.7% of non-VS patients (71.4% with DTG plus RPV and 52.2% with DTG plus b-DRV) achieved a viral load
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-12T11:32:35Z
      DOI: 10.1177/10600280211038504
       
  • Budesonide/Glycopyrrolate/Formoterol Fumarate Co-suspension Metered Dose
           Inhaler: A Triple Therapy for the Treatment of Chronic Obstructive
           Pulmonary Disease

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      Authors: Stefanie C. Nigro, Diana M. Sobieraj
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review current evidence on the use of a fixed-dose combination (FDC) of budesonide/glycopyrrolate/formoterol fumarate (BGFF) triple therapy delivered via metered dose inhaler (MDI) in patients with chronic obstructive pulmonary disease (COPD) and offer clinical practice insights.Data Sources:We used PubMed to conduct the literature search from 1946 through June 30, 2021, using budesonide, glycopyrrolate or glycopyrronium, and formoterol.Study Selection and Extraction:We included clinical trials in patients with COPD along with pharmacokinetic or pharmacodynamic studies.Data Synthesis:In all, 19 citations were included. BGFF MDI reduces the risk of exacerbations regardless of exacerbation history compared with dual bronchodilators or inhaled corticosteroid/long-acting β-agonist. Rescue inhaler use decreased, and patient-reported outcomes of symptoms and well-being improved with triple therapy. Mortality was decreased with the higher-dose BGFF MDI in comparison to dual bronchodilator therapy. Dysphonia and candidiasis were more common with BGFF MDI compared with dual bronchodilators, as was pneumonia.Relevance to Patient Care and Clinical Practice:BGFF MDI is the second FDC triple therapy approved for COPD treatment. BGFF MDI improves important patient outcomes in COPD, including exacerbation risk. The unique co-suspension technology allows delivery of 3 active ingredients in 1 inhaler, a potential benefit to overcome adherence and technique-related barriers. These benefits must be gently weighed against the increased risk of pneumonia.Conclusion:The findings from phase 3 trials support the efficacy and safety of triple therapy in COPD. Future studies are needed to confirm potential mortality benefit and the role of triple therapy in patients without an exacerbation history.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-12T11:28:42Z
      DOI: 10.1177/10600280211038353
       
  • The CYP3A5 and ABCB1 Gene Polymorphisms in Kidney Transplant Patients and
           Establishment of Initial Daily Tacrolimus Dosing Formula

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      Authors: Yuting He, Yixiao Ma, Qian Fu, Jianbo Liang, Xuegao Yu, Hao Huang, Liangying Zhong, Bin Huang
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundTacrolimus is an immunosuppressive drug used to prevent organ rejections. Many factors could influence blood concentration of tacrolimus.ObjectiveTo detect genotypes of cytochrome P450 3A5 (CYP3A5) and ABCB1 in kidney transplant patients and establish initial daily tacrolimus dosing formula based on genotypes of CYP3A5 and ABCB1 and patients’ clinical parameters.MethodsSequence specific primer polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism were used to detect genotypes of CYP3A5 and ABCB1. The blood cell, procalcitonin, C-reactive protein, height, weight, age, gender and other clinical parameters were recorded. Multiple linear regression analysis and Pearson correlation analysis were used to conduct date analysis.Results102 cases were enrolled in cohort 1, and there were 10 cases of CYP3A5 *1/*1 (9.8%), 28 cases of CYP3A5 *1/*3 (27.5%), and 64 cases of CYP3A5 *3/*3 (62.7%). The distributions of ABCB1 C3435T genotype were CC 36 (35.3%), CT 52 (51.0%), and TT 14 (13.7%). The distributions of ABCB1 G2677T/A genotype were GG 39 (38.2%), GT 40 (39.2%), and TT 23 (22.5%). The formula was 7.499 + (0.053 × Weight) − (0.029 × Hemoglobin concentration) − (1.045 × CYP3A5 genotype) (CYP3A5 genotype: *1/*1 type inputs 0, *1/*3 type inputs 1, *3/*3 type inputs 2). The predicted doses from the established formula had a significant correlation (r = 0.605) with actual clinical doses (P < 0.05).Conclusion and RelevanceHemoglobin concentration, weight, and CYP3A5 genotype should be considered using tacrolimus. The initial daily tacrolimus dosing formula established can make a good prediction.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-07T06:57:10Z
      DOI: 10.1177/10600280211023495
       
  • The Effect of Prearrest Acid-Base Status on Response to Sodium Bicarbonate
           and Achievement of Return of Spontaneous Circulation

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      Authors: Heath Mclean, Lindsey Wells, Jacob Marler
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundThe efficacy of sodium bicarbonate (SB) administration during in-hospital cardiac arrest (IHCA) for treatment of acidosis is not well described. The available literature has only evaluated out-of-hospital arrest events in patients with suspected acidosis caused by prolonged arrest.ObjectiveThis study evaluated SB and its effects on return of spontaneous circulation (ROSC) in patients experiencing IHCA, based on presence of acidosis at baseline as determined by prearrest bicarbonate levels.MethodsWe conducted a retrospective cohort study of patients who all received intravenous SB during IHCA. Patients with prearrest bicarbonate levels>21 mmol/L (nonacidotic group) were compared with those with prearrest bicarbonate levels ≤21 mmol/L (acidotic group) for the primary outcome of ROSC.ResultsA total of 225 patients (102 acidotic, 123 nonacidotic) were evaluated. Asystole (37.3% vs 34.1%; P = 0.63) and pulseless electrical activity (30.4% vs 29.3%; P = 0.85) were the most common presenting rhythms. There were no differences in ROSC in the overall population (53.9% vs 48.8%; P = 0.44) or between those who had early (within 20 minutes) or delayed (after 20 minutes) ROSC. Secondary outcomes, including cardiopulmonary resuscitation duration, epinephrine administration, and total SB, were similar between groups.Conclusions and RelevanceIn this cohort study, administration of SB for IHCA in patients with prearrest acidosis was not associated with increased incidence of ROSC compared with those without prearrest acidosis. Our data suggest that there may be no benefit to the administration of SB in the setting of IHCA, regardless of prearrest acidotic status. Further investigation into the effect of SB for treatment of acidosis in IHCA is warranted.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-06T04:33:32Z
      DOI: 10.1177/10600280211038393
       
  • Combination EGFR and RET Inhibition in Acquired Resistance to Osimertinib
           in EGFR-Mutant NSCLC

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      Authors: Jessica Freydman, Lynnette Henshaw, Jasmine V. Patel, Claire E. Smith, Peter C. Everett
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-04T04:43:28Z
      DOI: 10.1177/10600280211036909
       
  • Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell
           Therapy for the Treatment of Mantle Cell Lymphoma

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      Authors: Mary Kate Anderson, Annie Torosyan, Zachery Halford
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To identify and assess the current literature surrounding the safety, efficacy, and practical considerations of brexucabtagene autoleucel (brexu-cel) for the treatment of relapsed or refractory (r/r) mantle cell lymphoma (MCL).Data Sources:An English-based literature search was conducted using the terms “brexucabtagene autoleucel” AND “mantle cell lymphoma” OR “KTE-X19”in PubMed (inception through May 1, 2021), EMBASE (inception through May 1, 2021), and ClinicalTrials.gov.Study Selection and Data Extraction:All studies evaluating the use of brexu-cel in MCL were considered for inclusion.Data Synthesis:In the pivotal ZUMA-2 trial, brexu-cel demonstrated objective response and complete response rates of 85% and 59%, respectively. These results were consistent among high-risk subgroups. Noteworthy treatment-related adverse effects included grade ≥3 cytopenias (94%), immune effector cell–associated neurotoxicity syndrome (31%), and cytokine release syndrome (15%). Brexu-cel elicited a toxicity profile similar to that of other novel chimeric antigen receptor (CAR) T-cell products, with no new safety signals.Relevance to Patient Care and Clinical Practice:There are currently no head-to-head clinical trials evaluating brexu-cel against other approved subsequent-line options in r/r MCL. In a relatively small phase II trial, brexu-cel demonstrated impressive response rates in heavily pretreated patients, with few viable alternatives. Long-term safety and efficacy outcomes with brexu-cel are unknown. The prevention, identification, and management of unique CAR T-cell toxicities requires expert care from a well-trained interdisciplinary team.Conclusion:Brexu-cel has emerged as a viable treatment option in MCL. Additional studies are required to determine the optimal sequencing and place in therapy for brexu-cel in this highly heterogeneous, pathobiologically distinct, and incurable malignancy.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-08-03T04:39:13Z
      DOI: 10.1177/10600280211026338
       
  • Targeting the Myeloid Lineages and the Immune Microenvironment in
           Myelodysplastic Syndromes: Novel and Evolving Therapeutic Strategies

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      Authors: Clement Chung
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To discuss the recent and emerging data for novel targeted therapies in myelodysplastic syndromes (MDS).Data Sources:A literature search from January 2015 to June 2021 was performed using the key terms targeted therapies, myelodysplastic syndromes, DNA repair, erythroid differentiation therapy, epigenetic inhibitors, signal transduction inhibitors, and apoptosis-inducing agents.Study Selection and Data Extraction:Relevant clinical trials and articles in the English language were identified and reviewed.Data Synthesis:MDS are a heterogeneous group of malignant blood disorders affecting the bone marrow (BM), ultimately leading to BM failure, acute leukemia, and death. Selection of treatment is influenced by the severity of symptoms, cytopenia, cytogenetics, prognostic category, medical fitness, and patient preferences. Although current therapies such as erythropoiesis stimulating agents (ESAs) and hypomethylating agents (HMAs) help improve anemia and reduce transfusion burden, limited treatment options exist when patients experience treatment failure to ESAs or HMA. Recent regulatory approval of luspatercept, which targets the erythroid differentiation pathway, represents a major therapeutic advance in the management of anemia in MDS patients who are refractory to ESAs. Many investigational targeted therapies that aim at the myeloid lineage signaling pathway and the immune microenvironment are in active development.Relevance to Patient Care and Clinical Practice:This nonexhaustive review summarizes and describes the recent data for targeted therapies for MDS.Conclusion:The development of novel and investigational therapeutic agents continues to contribute to an improved understanding of tumor biology. The precise therapeutic role and timing of these agents remain to be elucidated.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-31T04:37:08Z
      DOI: 10.1177/10600280211036154
       
  • Reply: Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients
           Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality
           Without Increased Infection Risk

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      Authors: Xian Jie Cindy Chen, Diana Altshuler, Peter Spiegler, Shari B. Brosnahan
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-31T04:35:48Z
      DOI: 10.1177/10600280211036047
       
  • Comment: Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients
           Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality
           Without Increased Infection Risk

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      Authors: Brittany D. Bissell, Breanne Mefford, J. Chris Donaldson
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-31T04:33:35Z
      DOI: 10.1177/10600280211036040
       
  • Novel Use of Fostemsavir for 2 Multidrug-Resistant Persons With Human
           Immunodeficiency Virus

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      Authors: Patricia Pecora Fulco, Daniel Nixon, Denese C. Gomes
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-30T09:49:23Z
      DOI: 10.1177/10600280211035510
       
  • Evaluation of Bivalirudin as the Primary Anticoagulant in Patients
           Receiving Extracorporeal Membrane Oxygenation for SARS-CoV-2–Associated
           Acute Respiratory Failure

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      Authors: Brittany D. Bissell, Taylor Gabbard, Erica A. Sheridan, Maher A. Baz, George A. Davis, Ayesha Ather
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundExtracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population.ObjectiveThe purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19–associated respiratory failure.MethodsThis was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h.ResultsThere were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%.Conclusion and RelevanceIn the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-29T10:03:22Z
      DOI: 10.1177/10600280211036151
       
  • Addressing Barriers to Reducing Prescribing and Implementing Deprescribing
           of Sedative-Hypnotics in Primary Care

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      Authors: Lisa Burry, Justin Turner, Timothy Morgenthaler, Cara Tannenbaum, Hyung J. Cho, Evelyn Gathecha, Flora Kisuule, Abi Vijenthira, Christine Soong
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To describe interventions that target patient, provider, and system barriers to sedative-hypnotic (SH) deprescribing in the community and suggest strategies for healthcare teams.Data Sources:Ovid MEDLINE ALL and EMBASE Classic + EMBASE (March 10, 2021).Study Selection and Data Extraction:English-language studies in primary care settings.Data Synthesis:20 studies were themed as patient-related and prescriber inertia, physician skills and awareness, and health system constraints. Patient education strategies reduced SH dose for 10% to 62% of participants, leading to discontinuation in 13% to 80% of participants. Policy interventions reduced targeted medication use by 10% to 50%.Relevance to Patient Care and Clinical Practice:Patient engagement and empowerment successfully convince patients to deprescribe chronic SHs. Quality improvement strategies should also consider interventions directed at prescribers, including education and training, drug utilization reviews, or computer alerts indicating a potentially inappropriate prescription by medication, age, dose, or disease. Educational interventions were effective when they facilitated patient engagement and provided information on the harms and limited evidence supporting chronic use as well as the effectiveness of alternatives. Decision support tools were less effective than prescriber education with patient engagement, although they can be readily incorporated in the workflow through prescribing software.Conclusions:Several strategies with demonstrated efficacy in reducing SH use in community practice were identified. Education regarding SH risks, how to taper, and potential alternatives are essential details to provide to clinicians, patients, and families. The strategies presented can guide community healthcare teams toward reducing the community burden of SH use.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-24T04:57:54Z
      DOI: 10.1177/10600280211033022
       
  • 1% Tirbanibulin Ointment for the Treatment of Actinic Keratoses

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      Authors: Diem-Phuong D. Dao, Vikram Nath Sahni, Dev Ram Sahni, Esther A. Balogh, Ayman Grada, Steven R. Feldman
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveActinic keratoses (AKs) are cutaneous lesions that arise in sun-damaged skin. AKs may transform into squamous cell carcinoma in situ. Tirbanibulin 1% ointment is a new topical treatment for AKs, recently approved by the Food and Drug Administration.Data SourcesThe PubMed database was searched for articles published from 1960 to March 31, 2021, using the keywords tirbanibulin and Klisyri.Data ExtractionPhase 2 and phase 3 clinical trials were reviewed.Data SynthesisIn phase 2 clinical trials, 43% of patients treated with tirbanibulin experienced complete clearance by day 57 (43% [95% CI = 32, 54]). Across two phase 3 clinical trials (pooled data), complete (100%) clearance occurred in 49% of patients in tirbanibulin groups and in only 9% of the vehicle groups (difference, 41% points; 95% CI = 35 to 47; P < 0.001). Although no comparative studies are available, tirbanibulin is applied for a shorter duration (5 days) compared with diclofenac 3% gel, fluorouracil 5% cream, and imiquimod 3.75% cream. Adverse events were mild and included pruritus, application site pain, and local skin reactions. Systemic adverse events such as necrosis and angioedema, observed with other AK treatments such as fluorouracil and imiquimod, were not observed with tirbanibulin, thus giving tirbanibulin a favorable safety profile.Relevance to Patient Care and Clinical PracticeTirbanibulin effectively reduces AK burden and recurrence and has a favorable safety profile with mild adverse events. In comparison, imiquimod, 5-flourouracil, and diclofenac can result in necrosis, angioedema, and arthralgias.ConclusionWith a favorable safety profile and short regimen, tirbanibulin is an efficacious treatment for clinicians to utilize in their treatment toolbox when treating AKs on the face and scalp.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-24T04:55:19Z
      DOI: 10.1177/10600280211031329
       
  • Effectiveness, Durability, and Safety of Dolutegravir and Lamivudine
           Versus Dolutegravir, Lamivudine, and Abacavir in a Real-Life Cohort of
           HIV-Infected Adults

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      Authors: Inés Mendoza, Alicia Lázaro, Miguel Torralba
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Dolutegravir (DTG) plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment.Objective:To analyze the effectiveness, durability, and safety of 2-DR compared with DTG plus abacavir/lamivudine (3-DR).Methods:This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) patients who started 2-DR or 3-DR between July 1, 2018, and November 30, 2020. The primary end point was noninferiority, at 24 and 48 weeks, of 2-DR versus 3-DR regarding the percentage of patients with viral load (VL)≥50 and 200 copies/mL in TN (4% margin) and VL
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-23T06:10:01Z
      DOI: 10.1177/10600280211034176
       
  • Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune
           Checkpoint Inhibitors in Advanced Cancer Patients

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      Authors: Kangning Peng, Ken Chen, Benjamin A. Teply, Gary C. Yee, Paraskevi A. Farazi, Elizabeth R. Lyden
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH.Objective:To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non–small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma.Methods:This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS.Results:A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC.Conclusion and Relevance:Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-20T09:58:11Z
      DOI: 10.1177/10600280211033938
       
  • Orladeyo (Berotralstat): A Novel Oral Therapy for the Prevention of
           Hereditary Angioedema

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      Authors: Jason Powell, Chris Piszczatoski, Eric Rubido
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveThe purpose of this article is to review the available trials that led to the Food and Drug Administration (FDA) approval of berotralstat, an oral kallikrein inhibitor, for the prevention of hereditary angioedema (HAE) attacks.Data SourcesPubMed and ClincalTrials.gov were searched using key term berotralstat to identify phase III clinical trials related to the FDA approval of berotralstat from April 2018 to May 2021.Study Selection and Data ExtractionTrials selected were those that influenced the FDA approval of berotralstat or provided novel information regarding the safety and efficacy of this therapy in the treatment of HAE.Data SynthesisBoth APeX-2 and ApeX-J found clinically significant benefit with berotralstat 150 mg daily for reduction in HAE attacks when compared with placebo (1.31 vs 2.35, P < 0.001, and 1.11 vs 2.18, P < 0.001, attacks in the APeX-2 and APeX-J trials, respectively). APeX-2 also showed a statistically significant benefit for berotralstat 110 mg daily (1.65 vs 2.35 attacks [1.65 attacks, P = 0.024]).Relevance to Patient Care and Clinical PracticeAn advantage berotralstat has over the other approved therapies is that it is administered orally, which may garner patient preference because of ease of administration. Berotralstat has also shown a potential benefit in reducing the need for standard-of-care treatment for HAE attacks, which has not been studied with alternative agents.ConclusionsBerotralstat 150 mg daily has been proven safe and effective in clinical studies and appears to be a viable oral alternative to parenteral medications currently used in HAE prophylaxis.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-20T09:55:09Z
      DOI: 10.1177/10600280211032982
       
  • Underreported Risk of Lisinopril-Induced Angioedema in a Veteran
           Population

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      Authors: Whitley J. Whitehead, Jennifer Meyer Reid
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Lisinopril-induced angioedema (LIA) is a rare but serious adverse drug event (ADE) with a published incidence of 0.1% to 0.7%. It is well known that ADEs are widely underreported; however, LIA is one of the most reported ADEs within the Veterans Health Administration (VHA).Objective:To estimate the effect of underreporting on the risk of LIA within VHA.Methods:The reported risk of LIA was calculated from reports submitted to the Veterans Affairs (VA) Adverse Drug Event Reporting System (VA ADERS) and the number of veterans prescribed lisinopril. To estimate underreporting, local chart review identified cases of LIA that were compared to reports submitted. The underreporting rate was then applied to the national reported risk.Results:Locally, 68 reports of LIA were submitted of the 21 262 patients prescribed lisinopril, for a reported risk of 0.32%. Nationwide, 14 289 reports of LIA were submitted of the 3 109 661 patients prescribed lisinopril, for a crude reported risk of 0.46%. Of the 324 patients identified for chart review, 240 patients were diagnosed with LIA, suggesting that at least 71.7% of cases were unreported. When this underreporting rate is extrapolated to the national reported risk, a better estimate of the risk of LIA within VHA could increase to 1.6%.Conclusion and Relevance:When estimating the effect of underreporting, the risk of LIA increases to approximately 1.6% or 1 in 63 patients. Because this ADE may affect more patients than previously understood, providers may wish to take LIA into consideration when prescribing lisinopril.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-20T09:53:09Z
      DOI: 10.1177/10600280211032404
       
  • Treatment of Acute Gout Flares in the Emergency Department: Prescribing
           Patterns and Revisit Rates

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      Authors: Luigi Brunetti, Janaki Vekaria, Peter E. Lipsky, Naomi Schlesinger
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundThe incidence and health care costs of gout flares have increased in the United States. The increased costs may be a result of a lack of adherence to treatment guidelines and medication knowledge. Identifying causes for this trend is vital to mitigate inappropriate resource use.ObjectivesThe aim was to identify pharmacotherapy use related to gout treatment before, during hospital visit or stay, and on discharge in patients presenting to the emergency department (ED) with gout flares. Secondary end points included opioid use, revisit rates, and associated risk factors.MethodsWe performed a retrospective cohort study at a community teaching hospital ED. All consecutive patients visiting the ED from January 2016 to July 2019 with a primary diagnosis of gout flare were included. Data were extracted from the electronic medical records.ResultsThe analysis included 214 patients. Anti-inflammatory medication was not prescribed in 33.6% during the hospital visit and 29.6% of patients on discharge. History of opioid use (odds ratio [OR] = 3.3; 95% CI = 1.3-8.6; P = 0.014) and gastroesophageal reflux disease (OR = 3.5; 95% CI = 1.09-10.9; P = 0.035) were associated with opioid prescription on discharge. ED revisits within 90 days for any gout-related or non–gout-related cause were recorded in 16.8% of patients.Conclusion and RelevanceRoughly 30% of patients did not receive an anti-inflammatory on discharge, and opioids were frequently overused in gout management in the ED. There is an opportunity for further education of health care providers regarding gout treatment.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-20T09:51:09Z
      DOI: 10.1177/10600280211032295
       
  • Association Between Potentially Inappropriate Medications and 30-Day
           Post–Hospital Discharge Outcomes in US Veterans

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      Authors: Heather G. Allore, Danijela Gnjidic, Melissa Skanderson, Ling Han
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundPotentially inappropriate medication (PIMs) use is common in older inpatients and it may lead to increased risk of adverse drug events.ObjectivesTo examine prevalence of PIMs at hospital discharge and its contribution to health care utilization and mortality within 30-days of hospital discharge.MethodsThis was a prospective cohort of 117 570 veterans aged ≥65 years and hospitalized in 2013. PIMs at discharge were categorized into central nervous system acting (CNS) and non-CNS. Outcomes within 30-days of hospital discharge were: (1) time to first acute care hospital readmission, and all-cause mortality, (2) an emergency room visit, and (3) ≥3 primary care clinic visits.ResultsThe cohort’s mean age was 74.3 years (SD 8.1), with 51.3% exposed to CNS and 62.8% to non-CNS PIMs. Use of CNS and non-CNS PIMs, respectively, was associated with a reduced risk of readmission, with an adjusted hazard ratio (aHR) of 0.93 (95% CI = 0.89-0.96) for ≥2 (vs 0) CNS PIMs and an aHR of 0.85 (95% CI = 0.82-0.88) for ≥2 (vs 0) non-CNS PIMs. Use of CNS PIMs (≥2 vs 0) was associated with increased risk of mortality (aHR = 1.37 [95% CI = 1.25-1.51]), whereas non-CNS PIMs use was associated with a reduced risk of mortality (aHR = 0.75 [95% CI = 0.69-0.82]).Conclusion and RelevancePIMs were highly common in this veteran cohort, and the association with outcomes differed by PIMs. Thus, it is important to consider whether PIMs are CNS acting to optimize short-term posthospitalization outcomes.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-20T09:49:39Z
      DOI: 10.1177/10600280211032072
       
  • Delayed Rivaroxaban Elimination in Acute Kidney Injury and Shock Liver

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      Authors: Zachary S. Robinson, Katharine L. Madding, Dylan Magoto
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-14T10:12:06Z
      DOI: 10.1177/10600280211032293
       
  • Antibiotic Approvals in the Last Decade: Are We Keeping Up With
           Resistance'

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      Authors: Elias B. Chahine, John A. Dougherty, Krisy-Ann Thornby, Erenie H. Guirguis
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review the spectrum of activity, efficacy, safety, and role in therapy of all antibiotics and related biologics approved by the Food and Drug Administration (FDA) in the last decade.Data Sources:A literature search was performed using PubMed and Google Scholar (2010 to end May 2021) with the search terms’ name of the antibiotic or the biologic. Data were also obtained from the prescribing information, FDA, and ClinicalTrials.gov websites.Study Selection:All relevant English-language, late phase clinical trials assessing the safety and efficacy of the identified drugs were included. Review articles and references of retrieved articles were evaluated for relevant data.Data Synthesis:Antibiotic resistance is a public health crisis, and antibiotic development is imperative to outpace the ability of bacteria to develop resistance. Only 17 new systemic antibiotics and 1 related biologic have been approved by the FDA since 2010. Among these drugs, 14 were approved for common bacterial infections, 1 was approved for Clostridioides difficile infection (CDI), 1 was licensed to prevent CDI recurrence, and 2 were approved for drug-resistant tuberculosis. Very few antibiotics are in clinical development.Relevance to Patient Care and Clinical Practice:The arrival of these new antibiotics was welcomed with great enthusiasm, particularly when they met previously unmet medical needs. Unfortunately, the majority of them represent modifications to existing chemical structures rather than new drug classes. Despite the availability of these antibiotics, managing patients with deep-seated infections and those with extensively resistant gram-negative organisms remains challenging.Conclusions:The number of new antibiotics and their indications are not keeping up with resistance and the needs of the patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-14T10:10:58Z
      DOI: 10.1177/10600280211031390
       
  • Safety, Efficacy, and Cost of 0.4-mg Versus 2-mg Intranasal Naloxone for
           Treatment of Prehospital Opioid Overdose

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      Authors: John Thompson, Jenna Salter, Peter Bui, Logan Herbert, David Mills, Deborah Wagner, Christine Brent
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundIntranasal naloxone is commonly used to treat prehospital opioid overdose. However, the optimal dose is unclear, and currently, no study exists comparing the clinical effect of intranasal naloxone at different doses.ObjectiveThe goal of this investigation was to compare the safety, efficacy, and cost of 0.4- versus 2-mg intranasal naloxone for treatment of prehospital opioid overdose.MethodsA retrospective, cross-sectional study was performed of 218 consecutive adult patients receiving intranasal naloxone in 2 neighboring counties in Southeast Michigan: one that used a 0.4-mg protocol and one that used a 2-mg protocol. Primary outcomes were response to initial dose, requirement of additional dosing, and incidence of adverse effects. Unpooled, 2-tailed, 2-sample t-tests and χ2 tests for homogeneity were performed with statistical significance defined as P
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-07T06:37:22Z
      DOI: 10.1177/10600280211030918
       
  • Epidemiology of Infections With Rothia Species in an Academic Medical
           Center

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      Authors: Brittany D. Bissell, Alexander Kreimer, David S. Burgess
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-05T07:16:11Z
      DOI: 10.1177/10600280211030332
       
  • Challenges in Treating Chlamydia trachomatis, Including Rectal Infections:
           Is It Time to Go Back to Doxycycline'

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      Authors: S. Lena Kang-Birken
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To evaluate recent publications on efficacy of single-dose azithromycin and 7-day doxycycline when treating Chlamydia trachomatis.Data Sources:A literature search of MEDLINE, EMBASE, PubMed, and Cochrane library was conducted (1990 to June 13, 2021) using the terms: Chlamydia trachomatis, genital chlamydia, rectal chlamydia, extragenital chlamydia, azithromycin, doxycycline, and treatment guidelines. ClinicalTrials.gov was searched to identify ongoing trials.Study Selection and Data Extraction:English language studies, including controlled studies, retrospective analyses, systematic reviews, meta-analyses, and case reports, reporting microbiological or clinical outcomes in adolescents and adults were considered.Data Synthesis:Systemic reviews and meta-analyses of randomized trials reported azithromycin efficacy of 96% to 97% in genital chlamydia. However, reports of treatment failure have emerged, especially among symptomatic males, with an increased risk of microbiological failure after azithromycin than doxycycline (relative risk = 2.45; 95% CI = 1.36-4.41). Retrospective analyses and prospective observational cohort studies reported lower efficacy range following azithromycin than doxycycline (74%-87% vs 92%-100%, respectively) in rectal chlamydia. First randomized controlled trial comparing azithromycin and doxycycline reported significantly higher microbiological cure following doxycycline, with absolute difference of 26% (95% CI = 16%-36%; P < 0.001). The proposed 2021 Centers for Disease Control and Prevention treatment guidelines designate doxycycline as the preferred agent for treatment at any site.Relevance to Patient Care and Clinical Practice:A growing body of evidence for treatment failure following azithromycin, especially in rectal chlamydia supports updating current practice.Conclusions:Doxycycline continues to achieve high efficacy in genital and rectal chlamydia. Clinicians should consider efficacy with convenience of dosing regimen, medication compliance, and sexual behavior risks when treating chlamydia infections.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-03T12:10:49Z
      DOI: 10.1177/10600280211029945
       
  • Analysis of the Frequency and Onset Time of Hyponatremia/Syndrome of
           Inappropriate Antidiuretic Hormone Induced by Antidepressants or
           Antipsychotics

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      Authors: Koki Takeda, Chika Kobayashi, Taketo Nakai, Teruki Oishi, Akira Okada
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundHyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) is a potentially fatal adverse effect of antidepressants (ADs) and antipsychotics (APs), although its frequency and onset time have not been well documented.ObjectiveTo analyze the frequency and onset time of AD- or AP-induced hyponatremia/SIADH.MethodsWe used plural data-mining techniques to search the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports on hyponatremia/SIADH induced by psychotropic drugs from January 2004 to June 2020. For each item, we assessed the reporting odds ratio, 95% CI, median onset time, and Weibull distribution parameters.ResultsWe identified 36 422 reports related to hyponatremia/SIADH. Signals were detected for all psychotropic drugs that we analyzed, except for clozapine. The median onset time of total AD-induced hyponatremia/SIADH was shorter than that of AP. For all ADs and APs except clozapine, hazards were considered to be the early failure type. In contrast, the hazard of clozapine was considered to be the random failure type. The limitations of this study included several reporting biases and the presence of confounding variables, particularly age.Conclusion and RelevanceMost ADs and APs were found to be associated with a risk for hyponatremia/SIADH. In addition, sufficient attention should be paid to signs of hyponatremia/SIADH in the early phase when most ADs and APs are administered. These data are potentially useful for determining AD- or AP-induced hyponatremia/SIADH in the early stage and for preventing its further aggravation into a serious condition.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-02T06:05:34Z
      DOI: 10.1177/10600280211030270
       
  • Overcoming Cough and Angioedema: Advocating for the Use of ARBs Over ACE
           Inhibitors

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      Authors: Melanie Lam, Anelsa Beqo, Ricky Thumar
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors have comparable efficacy, but ARBs have a preferential safety profile with particular regard to cough and angioedema. Although guidelines have historically advocated for ACE inhibitor use before ARBs simply because of earlier market entry, data accumulation, and generic availability, updated verbiage advises an “ACE inhibitor or ARB” recommendation, as opposed to the classic “ACE inhibitor then ARB” approach. Despite these updates, clinical inertia in favor of ACE inhibitor use before ARBs overwhelmingly remains. Prescribers and educators should consider an “ARBs only” mentality, especially in high angioedema-risk groups such as black patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-01T08:28:50Z
      DOI: 10.1177/10600280211029952
       
  • Safety of Rapid Infliximab Biosimilar Infusions in Patients With
           Inflammatory Bowel Disease

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      Authors: Ji Yoon Kim, Shubha Bhat
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundThe biosimilar landscape for inflammatory bowel disease (IBD) continues to grow, with several biosimilar products for originator infliximab now available. The rapid infusion of originator infliximab and infliximab-dyyb has been shown to be well tolerated; however, the tolerability of rapid infusion in patients receiving infliximab-abda, another infliximab biosimilar, or in those who have switched among originator infliximab and biosimilars remains unknown.ObjectiveWe aimed to evaluate the safety of rapid infusion in patients with IBD who received infliximab-abda or underwent switches with infliximab products.MethodsWe conducted a retrospective observational study of all infliximab-related infusion encounters for patients ≥18 years with IBD who received their infusion over 30 to 90 minutes at our institution between March 1, 2020, and September 30, 2020. Patient, disease, and treatment characteristics were collected. The primary outcome was infusion reactions.ResultsA total of 377 infusion encounters for 96 unique patients were evaluated. Within the study cohort, 16% of patients were treated with originator infliximab, 42% with infliximab-dyyb, and 2% with infliximab-abda. The remaining 41% of patients received at least 2 infliximab products during the study period, primarily infliximab-dyyb and infliximab-abda. Approximately 54% and 42% of infusions encounters included premedication and immunomodulator use. Within the 377 infusion encounters, no infusion reactions were noted.Conclusion and RelevanceRapid infusion of infliximab biosimilars (including infliximab-abda) and in patients who have switched among originator infliximab and biosimilars is well tolerated. Future studies should assess clinical impact and outcomes of rapid infusion with biosimilars.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-07-01T07:30:58Z
      DOI: 10.1177/10600280211029345
       
  • Pronounced Regional Disparities in United States Methadone Distribution

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      Authors: John A. Furst, Nicholas J. Mynarski, Kenneth L. McCall, Brian J. Piper
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Methadone is an evidence-based treatment for opioid use disorder (OUD) and pain management. Methadone for OUD may be difficult for some patients to access, particularly those in rural areas.Objective:The purpose of this study was to characterize methadone distribution patterns between 2017 and 2019 across the United States.Methods:The US Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System was used to acquire the number of opioid treatment programs (OTPs) per state and methadone distribution weight in grams. Methadone distributions by weight, corrected for state population and number of OTPs, were compared from 2017 to 2019 between states, within regions, and nationally.Results:The national distribution of methadone increased +12.3% for OTPs but decreased −34.6% for pain. Whereas all states saw a decrease in pain distribution, the Northeast showed a significantly smaller decrease than all other regions. Additionally, the majority of states experienced an increase in distribution for OTPs, and most states demonstrated a relatively stable or increasing number of OTPs, with an +11.5% increase nationally. The number of OTPs per 100K state population ranged from 2.1 in Rhode Island to 0.0 in Wyoming.Conclusion and Relevance:Although methadone distribution for OUD was increasing in the United States, the pronounced regional disparities identified warrant further consideration to improve patient access to this evidence-based pharmacotherapy, particularly in the Midwest and West regions. Greater implementation of telehealth and involvement of primary care into opioid treatment practice offer possible solutions to eliminating geographical treatment barriers.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-29T11:53:04Z
      DOI: 10.1177/10600280211028262
       
  • Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients
           Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality
           Without Increased Infection Risk

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      Authors: Shari B. Brosnahan, Xian Jie Cindy Chen, Juri Chung, Diana Altshuler, Shahidul Islam, Sarun V. Thomas, Megan D. Winner, Allison A. Greco, Jasmin Divers, Peter Spiegler, Daniel H. Sterman, Sam Parnia
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundSevere hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven.ObjectivesThe primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure.MethodsA multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit.ResultsThe steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection.Conclusion and RelevanceCombination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-28T11:39:56Z
      DOI: 10.1177/10600280211028882
       
  • Continuous Opioid Infusions in Critically Ill Children

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      Authors: Jillian Bybee, Dave Procaccini, Sapna R. Kudchadkar
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-25T06:17:56Z
      DOI: 10.1177/10600280211028671
       
  • “Reply: Conversion From Continuous Infusion Fentanyl to Hydromorphone in
           the Pediatric Intensive Care Unit”

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      Authors: Maura Harkin, Jamie Miller, Sin Yin Lim, Stephen Neely, Christina Walsh, Peter N. Johnson
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-24T03:42:13Z
      DOI: 10.1177/10600280211028672
       
  • Interventions in an Ambulatory Setting to Prevent Progression to Severe
           Disease in Patients With COVID-19: A Systematic Review

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      Authors: Eamon O Murchu, Susan Spillane, Paula Byrne, Michelle O’Neill, Patricia Harrington, Máirín Ryan
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To conduct a systematic review on the effectiveness and safety of pharmacological and nonpharmacological interventions, in the ambulatory setting, aimed at preventing severe disease in patients with COVID-19.Data Sources:Electronic databases (PubMed, EMBASE, and EuropePMC) were searched on January 6, 2021.Study Selection and Data Extraction:A systematic review was conducted, adhering to PRISMA guidelines. The quality of individual trials was assessed using the Cochrane Risk-of-Bias Tool 2, and the certainty of evidence was assessed using GRADE.Data Synthesis:The collective search retrieved 3818 citations. Eight trials relating to 9 pharmacological interventions were identified. No evidence for nonpharmacological interventions was identified. Low certainty evidence of effectiveness in preventing severe disease was found for fluvoxamine (absolute difference: −8.7%; 95% CI: −1.8% to −16.4%) and bamlanivimab plus etesevimab (absolute difference: −4.9%; 95% CI: −0.8% to −8.9%). Both trials were limited by small sample sizes and short durations of follow-up. In addition, very low certainty evidence of effect was found for ivermectin plus doxycycline and sulodexide. Based on published data, insufficient evidence of effect was found for bamlanivimab (monotherapy), casirivimab plus imdevimab, ivermectin (monotherapy), nitazoxanide, and peginterferon lambda.Relevance to Patient Care and Clinical Practice:This review assessed all ambulatory treatments for COVID-19 that may improve patient outcomes and reduce hospitalizations.Conclusion:Recent trials have shown promising results for a number of pharmacological agents to treat COVID-19 in the ambulatory setting. However, larger, more robust trials are needed to support the routine use of these agents outside of monitored clinical trials.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-23T04:18:37Z
      DOI: 10.1177/10600280211028242
       
  • Abametapir for the Treatment of Head Lice: A Drug Review

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      Authors: Alexander D. Woods, Caroline L. Porter, Steven R. Feldman
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveThis article reviews the pharmacology, safety, efficacy, and clinical importance of abametapir 0.74% (Xeglyze) for the treatment of head lice.Data SourcesFrom 2020 to May 2021, a systematic review of the MEDLINE and EMBASE databases was conducted using the terms abametapir, Xeglyze, Ha44, and head lice. Bibliographies, Food and Drug Administration (FDA) drug package inserts, and ClinicalTrials.gov were searched for further information.Study Selection and Data ExtractionAll relevant full-text articles in English were considered for inclusion, with a final article date range of 1999 to 2020.Data SynthesisAbametapir chelates heavy metal cations and inhibits metalloproteinases critical to louse ova development, hatching, and adult survival. In phase II, abametapir had direct ovicidal activity inhibiting 100% of treated louse eggs from hatching, compared with 64% in the vehicle-treated group. In two identical phase III clinical trials, subjects treated with a single 10-minute application of abametapir had greater treatment success compared with vehicle-treated subjects, with 81.1% success versus 50.9% in study 1 (P = 0.001) and 81.8% versus 47.2% in study 2 (P < 0.001). Abametapir was well tolerated, with only mild adverse effects.Relevance to Patient Care and Clinical PracticeAbametapir is a newly FDA-approved, single-application treatment for head lice in patients aged 6 months and older. This review highlights the safety and efficacy of abametapir in the treatment of head lice.ConclusionsIn the wake of increasing widespread resistance to first-line treatment options, abametapir offers a safe and effective new treatment option for head lice infestations.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-23T04:14:33Z
      DOI: 10.1177/10600280211027968
       
  • Semaglutide for Weight Loss

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      Authors: Nicholas W. Carris, Eric A. Dietrich
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-23T04:08:36Z
      DOI: 10.1177/10600280211027204
       
  • Impact of Intravenous Opioid Shortage on Managing Pain Crisis in Sickle
           Cell Disease

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      Authors: Jin Han, Santosh L. Saraf, Michel Gowhari, Faiz Ahmed Hussain, Shivi Jain, Laura Kavoliunaite, Robert E. Molokie, Victor R Gordeuk
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-19T09:58:58Z
      DOI: 10.1177/10600280211024524
       
  • Patterns of Pharmaceutical Industry Marketing to Physicians for
           Direct-Acting Antivirals, 2013 Through 2019

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      Authors: Shangqing Jiang, Timothy S. Anderson, Zachary A. Marcum
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-18T12:02:02Z
      DOI: 10.1177/10600280211027242
       
  • Potential Dexamethasone–Direct Oral Anticoagulant Drug Interaction: Is
           This a Concern in COVID'

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      Authors: Maureen A. Smythe, Carly Burns, Qianyue Liu, Candice L. Garwood
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo evaluate the literature on a potential dexamethasone–direct oral anticoagulant (DOAC) drug interaction and provide management considerations with COVID hypercoagulability.Data SourcesA search of EMBASE, PubMed, and Google Scholar (January 1990 to May 2021), limited to the English language, using applicable search terms resulted in 137 articles, with 21 relevant articles included. Regulatory agency and clinical guidance documents were also reviewed.Study Selection and Data ExtractionIncluded articles describe in vitro or in vivo animal or human data for dexamethasone induction of cytochrome P450 (CYP) 3A4 or P-glycoprotein (P-gp).Data SynthesisDexamethasone has the potential to interact with the DOACs via CYP3A4 and/or P-gp induction. Only apixaban and rivaroxaban have CYP3A4 metabolism. Dexamethasone can increase CYP3A4 activity by up to 70% and reduce the area under the concentration-time curve (AUC) of CYP3A4 substrates by>40%, which is consistent with criteria for a weak CYP inducer. In rodents, dexamethasone P-gp induction is associated with AUC reductions of 20% to 50%. Human data are lacking.Relevance to Patient Care and Clinical PracticeSevere COVID-19 infection is associated with hypercoagulability. Although heparins are the preferred anticoagulants for hospitalized COVID-19 patients, DOACs are being utilized. Dexamethasone is recommended for hospitalized COVID-19 patients requiring supplemental oxygen. The concurrent use of dexamethasone and apixaban or rivaroxaban in such patients carries the potential for reduced anticoagulant effect during a state of heightened thrombotic risk.ConclusionsConcurrent use of dexamethasone and apixaban or rivaroxaban in hospitalized COVID-19 patients with laboratory evidence of COVID coagulopathy should be avoided until higher-quality data are available.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-17T09:43:05Z
      DOI: 10.1177/10600280211025042
       
  • Efficacy of Metformin in Patients With Breast Cancer Receiving
           Chemotherapy or Endocrine Therapy: Systematic Review and Meta-analysis

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      Authors: Kayoko Morio, Yasuko Kurata, Nobuko Kawaguchi-Sakita, Akihiro Shiroshita, Yuki Kataoka
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundPrevious studies have suggested that metformin might improve survival outcomes in patients with breast cancer. However, findings on the efficacy of metformin with chemotherapy or endocrine therapy are inconsistent.ObjectiveTo clarify the efficacy of metformin with chemotherapy or endocrine therapy in breast cancer patients according to the treatment setting, including neoadjuvant, adjuvant, and metastasis/recurrence.MethodsWe systematically searched for randomized controlled trials (RCTs) in MEDLINE, CENTRAL, and EMBASE from inception through July 2020. Overall survival (OS), progression-free survival (PFS), and hypoglycemia rate were the primary outcomes. Secondary outcomes included severe adverse events (SAEs) and relapse-free survival. We used the Grading of Recommendations Assessment, Development, and Evaluation approach and performed a meta-analysis to evaluate the efficacy and safety of metformin with chemotherapy and endocrine therapy in patients with breast cancer.ResultsOur systematic review included 412 participants from 5 trials. Metformin showed little to no difference in OS (hazard ratio [HR] = 1.13; 95% CI = 0.71-1.81; certainty of evidence [COE], moderate) and PFS (HR = 1.14; 95% CI = 0.86-1.50; COE, moderate) in patients with metastasis/recurrence. The evidence was very uncertain about the effect of metformin on survival outcomes in patients who received metformin with neoadjuvant or adjuvant treatment. Metformin showed little to no difference in hypoglycemia and SAEs.Conclusion and RelevanceMetformin should be discouraged routinely in nondiabetic patients with metastatic/recurrent breast cancer. Further RCTs are needed to verify whether metformin with chemotherapy or endocrine therapy results in significant clinical benefits in the neoadjuvant or adjuvant setting.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-17T09:42:57Z
      DOI: 10.1177/10600280211025792
       
  • Impact of Weight-Band Dosing of Tinzaparin for Venous Thromboembolism
           Prophylaxis on Persistent Wound Drainage in Adult Patients Undergoing Hip
           and Knee Arthroplasty

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      Authors: Cassandra Cooper, Ouida Antle, Jennifer Lowerison, Deonne Dersch-Mills, Ashley Kenny
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Persistent wound drainage and venous thromboembolism (VTE) are potential complications of total joint arthroplasty, and these risks can be challenging to balance in clinical practice. Anecdotal observation has suggested that following joint arthroplasty, persistent wound drainage occurs more frequently with higher body weight and higher doses of tinzaparin when compared with lower body weight and lower doses of tinzaparin.Objective:The overall purpose of this study was to describe the impact of a tinzaparin weight-band dosing table for VTE prophylaxis on wound healing, thrombosis, and bleeding outcomes in patients undergoing total joint arthroplasty.Methods:This retrospective chart review included patients who underwent total hip or knee arthroplasty and received tinzaparin for thromboprophylaxis per their weight-banding category. The primary outcome was the incidence of persistent wound drainage. Secondary outcomes include the occurrence of VTE and clinically important bleeding during hospital admission.Results:A total of 231 patients were included in the analysis. There was no significant difference in persistent wound drainage between the 3 weight categories, and there were no differences in rates of VTE or clinically important bleeding. Concurrent use of low-dose acetylsalicylic acid was associated with a 3-fold increased risk of persistent wound drainage (risk ratio = 3.35; 95% CI = 2.14-5.24; P = 0.00003).Conclusion and Relevance:In joint arthroplasty patients, we observed no significant difference in rates of persistent wound drainage between various weight categories receiving different weight-banded doses of tinzaparin. Our results do not suggest that the current weight-band dosing table for tinzaparin needs to be adjusted to optimize patient outcomes.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-16T07:03:11Z
      DOI: 10.1177/10600280211024294
       
  • A Galvanizing Solution: Colonoscopy Bowel Preparation as a Trigger for
           Supraventricular Tachycardia

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      Authors: Marvin Kajy, Preeti Ramappa
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Polyethylene glycol (PEG)-based solutions are among the most commonly used bowel preparation regimens for colonoscopy. Although these solutions are well tolerated, rare adverse cardiac events have been reported.Objectives:We sought to identify the characteristics that may predispose patients to develop supraventricular tachycardia (SVT) after ingestion of GoLYTELY (PEG 3350 and electrolytes oral solution) in anticipation for their colonoscopy.Methods:We performed a retrospective observational cohort study of the electronic medical record of all patients who developed SVT after ingestion of GoLYTELY solution from April 2012 to March 2019 at the John D. Dingell VA Medical Center. Clinical data were obtained through review of medical records.Results:We identified 16 patients with new-onset SVT after ingestion of bowel preparation solution before undergoing the colonoscopy procedure. In all, 12 (75%) patients developed atrial fibrillation, 3 (18.8%) patients developed atrial tachycardia, and 1 patient (6.3%) developed atrial flutter. Most patients were male (93.8%), and the mean age was 69 ± 8.2 years. The commonly associated comorbidities were hypertension (87.5%), hyperlipidemia (56.3%), and diabetes (37.5%). Laboratory testing demonstrated a normal electrolyte panel and thyroid stimulating hormone level. A significant percentage of patients had dilated atria and left-ventricular hypertrophy on echocardiogram.Conclusion:Our case series suggests that there may be certain individuals who are predisposed to development of atrial arrhythmias, more so than others, after ingestion of PEG based solution for colonoscopy. We hypothesize that the combination of atrial dilation, sympathovagal discharge, and transient electrolyte shifts at the cellular level led to the development of SVTs.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-14T06:17:49Z
      DOI: 10.1177/10600280211023808
       
  • Ubrogepant: An Oral Calcitonin Gene-Related Peptide (CGRP) Receptor
           Antagonist for Abortive Migraine Treatment

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      Authors: Madell Nedd, Scott Garland, Nathan Falk, Ashley Wilk
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo review the pharmacology, efficacy, and safety of ubrogepant as an abortive migraine treatment.Data SourcesA literature search of MEDLINE and PubMed was performed (January 2006 through May 2021) using the following search terms: ubrogepant, calcitonin gene related peptide, and abortive migraine therapy.Study Selection and Data ExtractionRelevant studies evaluating ubrogepant’s pharmacology, efficacy, and safety in humans for the treatment of migraine were consideredData SynthesisUbrogepant is a calcitonin gene-related peptide receptor antagonist approved by the Food and Drug Administration for the acute treatment of migraine via data from ACHIEVE I and II. From ACHIEVE I, ubrogepant demonstrated superiority to placebo in freedom from migraine pain at 2 hours postdose (50-mg dose: odds ratio [OR] = 1.83, 95% CI = 1.25-2.66; 100-mg dose: OR = 2.04, 95% CI = 1.41-2.95) and freedom from most bothersome symptom (MBS; 50-mg dose: OR = 1.70, 95% CI = 1.27-2.28; 100-mg dose: OR = 1.63, 95% CI = 1.22-2.17). ACHIEVE II trial demonstrated efficacy of ubrogepant 50 mg compared with placebo (2-hour pain freedom: OR = 1.62, 95% CI = 1.14-2.29; 2-hour MBS freedom: OR = 1.65, 95% CI = 1.25-2.20).Relevance to Patient Care and Clinical PracticeUbrogepant is a viable option for patients who are unable to tolerate nonsteroidal anti-inflammatory drug or triptan therapy because of ineffective relief or contraindications that limit use.ConclusionsUbrogepant is a well-tolerated effective abortive migraine treatment that bridges a gap in therapy for many patients who previously could not tolerate other first-line treatments.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-10T09:12:42Z
      DOI: 10.1177/10600280211023810
       
  • Comparison of Early Versus Late Initiation of Hydrocortisone in Patients
           With Septic Shock in the ICU Setting

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      Authors: David Ragoonanan, Bryan Allen, Chad Cannon, Kathleen Rottman-Pietrzak, Abdel Bello
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Multiple publications demonstrate an association between time to initiation of corticosteroids and outcomes such as mortality and reversal of shock. However, the optimal time to initiate hydrocortisone remains unknown.Objective:To evaluate the impact of early versus late initiation of hydrocortisone in septic shock patients.Methods:A retrospective, multicentered, observational study was conducted. Adults admitted from July 1, 2014, to August 31, 2019, diagnosed with septic shock receiving vasopressors and low-dose hydrocortisone were evaluated. Participants were divided into the “early” group if hydrocortisone was initiated within 12 hours or “late” group if initiated after 12 hours of vasopressor initiation. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included in-hospital mortality, intensive care unit (ICU) and hospital length of stay (LOS), vasopressor utilization, fluids administered, and need for renal replacement therapy.Results:A total of 198 patients were identified for inclusion in this propensity score–weighted cohort: 99 in the early group and 99 in the late group. Early initiation was associated with shorter time to vasopressor discontinuation compared with late initiation (40.7 vs 60.6 hours; P = 0.0002). There was also a reduction in ICU LOS (3.6 vs 5.1 days; P = 0.0147) and hospital LOS (8.9 vs 10.9 days; P = 0.0220) seen in the early group. There was no difference in mortality between groups.Conclusion and Relevance:In this propensity-matched cohort, administration of hydrocortisone within 12 hours from the onset of septic shock was associated with improved time to vasopressor discontinuation and reduced ICU and hospital LOS.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-10T09:12:33Z
      DOI: 10.1177/10600280211021103
       
  • Measurement of Pharmacist-Physician Collaborative Care on Therapeutic
           Inertia in Patients With Type 2 Diabetes

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      Authors: Kevin Cowart, Nnadozie Emechebe, Rashmi Pathak, Lucas Abbruzese, James Hann, Andie Lloyd, Richard Roetzheim, Janice Zgibor, Wendy H. Updike
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundTeam-based care practice models have been shown to improve diabetes-related therapeutic inertia, yet the method and type of antidiabetic treatment intensification (TI) leading to improvements in glycemic control are not well understood.ObjectiveTo evaluate time to TI in a pharmacist-physician practice model (PPM) as compared with usual medical care (UMC), explore the method and type of antidiabetic TI, and evaluate achievement of hemoglobin A1C (A1C) goal among each cohort.MethodsThis was a retrospective cohort study conducted between January 1, 2017, and December 31, 2018. Median time to TI was calculated and compared between patients in the PPM and UMC groups using the log rank test. Descriptive statistics were used to evaluate the method and type of TI and A1C goal achievement.ResultsA total of 56 patients were included. The median (interquartile range) time to antidiabetic TI among the PPM cohort was 37.5 days (8, 216.5), as compared with 142 days (16, 465) in the UMC cohort (P = 0.19). At 1 year post–index date, 25% of patients in the PPM cohort reached their A1C goal compared with 18.8% of patients in the UMC cohort. This effect was maintained in the subgroup (n = 49) of patients receiving TI (23.1% vs 17.8%).Conclusion and RelevanceA shorter time to TI and improvement in A1C goal achievement was observed with pharmacist-physician care compared with UMC. These findings suggest that pharmacist-physician care may be one of several interventions necessary to overcome therapeutic inertia in diabetes care.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-09T09:11:14Z
      DOI: 10.1177/10600280211023492
       
  • Analysis of the Clinical Characteristics of Dipeptidyl Peptidase-4
           Inhibitor–Induced Bullous Pemphigoid

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      Authors: Linli Sun, Chunxia Wang, Cuifang Wu, Yulu Zhou, Chunjiang Wang
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo analyze and discuss the clinical characteristics of dipeptidyl peptidase-4 inhibitor (DPP4i)-induced bullous pemphigoid (BP).Data SourcesWe collected case reports of DPP4i-induced BP by searching databases from 2006 to mid-May 2021, as a retrospective analysis.Study Selection and Data ExtractionRelevant case reports and case analyses of DPP4i-induced BP were included.Data SynthesisThe median time of symptom onset was 9 months (range 0.5-59 months). BP most often occurred in patients receiving vildagliptin (52.63%) followed by linagliptin (27.19%) and sitagliptin (17.54%). Tense bullae and blisters (85.51%) and erythema (82.61%) on the extremities and trunk were the most common presenting symptoms. In total, 64.06% of BP patients were anti-BP180 autoantibody positive, 58.97% were BP180NC16a autoantibody positive, and 31.25% were anti-BP230 autoantibody positive. Skin biopsy revealed subepidermal bulla eosinophil infiltration in 93.85% of BP patients, lymphocyte infiltration in 56.93%, and neutrophil infiltration in 44.62%. Direct immunofluorescence was positive in 98.94% of BP patients with linear deposition of IgG (97.80%) and/or complement C3 (98.94%) along the basement membrane zone. Indirect immunofluorescence was positive in 87.88% of BP patients. Complete remission of BP was achieved in 83.64% of patients on DPP4i withdrawal and after 4 months (range 0.13-72 months) of follow-up.Relevance to Patient Care and Clinical PracticeThis review analyzes and discusses the clinical characteristics of DPP4i-induced BP and provides a reference for the safe and reasonable clinical application of DPP4i.ConclusionsDPP4i drugs are related to the occurrence of BP in diabetic patients, especially elderly men taking vildagliptin.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-09T09:11:02Z
      DOI: 10.1177/10600280211022722
       
  • Lead in Mineral or Multivitamin-Multimineral Products

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      Authors: C. Michael White
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveAssess the current daily interim reference level of lead and the amount contained in current mineral and multivitamin-multimineral (MVM) products.Data SourcesPubMed search from 1980 to May 15, 2021, limited to the English language, via the search strategy ((mineral OR multivitamin OR calcium OR iron OR magnesium OR copper OR zinc OR chromium OR selenium) AND (heavy metals OR Pb OR lead)).Study Selection and Data ExtractionNarrative review of studies assessing lead content in mineral or MVM products.Data SynthesisProducts containing different calcium forms (dolomite, bone meal, natural carbonate) have historically had higher lead levels than others (refined carbonate, lactate, gluconate, acetate, sevelamer), but the gap has closed considerably since the year 2000. Although only limited assessments of magnesium and zinc supplements have been conducted, no alarming average lead amounts were found. MVM products assessed since 2007 had low median or mean lead concentrations. However, large interproduct differences exist, with many products having very little lead and some products having concerning amounts.Relevance to Patient Care and Clinical PracticeIt is difficult for pharmacists and consumers to know the amount of lead in an actual product unless it is tested in an independent third-party lab. The United States Pharmacopeia and NSF International will provide a seal on the products stating that the products have a low level of lead, but even so, children could receive more lead than the Food and Drug Administration’s Interim Reference Level.ConclusionsThe threat from lead exposure in mineral and MVM products have diminsihed considerably over time but some products can still have excessive amounts. Without third-party testing, it is difficult for clinicians and consumers to know which outlier products to avoid.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-07T05:46:39Z
      DOI: 10.1177/10600280211023328
       
  • Impact of Prior-to-Admission Methicillin-Resistant Staphylococcus aureus
           Nares Screening in Critically Ill Adults With Pneumonia

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      Authors: Mariana G. Mallidi, Giles W. Slocum, Gary D. Peksa, Joshua M. DeMott
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundThe high negative predictive value (NPV) of a negative nasal methicillin-resistant Staphylococcus aureus (MRSA) result in suspected MRSA pneumonia is well established; however, data are limited on the NPV of samples collected prior to hospital admission for critically ill patients.ObjectiveTo evaluate the predictive characteristics of MRSA nares screening performed prior to hospital admission in critically ill adult patients diagnosed with pneumonia.MethodsA retrospective analysis was conducted in critically ill patients with pneumonia and MRSA nares screening within 60 days of respiratory culture. The primary outcome was NPV of MRSA nares for MRSA pneumonia using samples within 60 days compared to in-hospital respiratory cultures. A sensitivity analysis was performed for samples within 30 days. Secondary outcomes were prevalence, positive predictive value (PPV), sensitivity, specificity, and MRSA pneumonia risk factors.ResultsThe NPV for MRSA nares screening collected prior to hospital admission was high at 98% (95% CI = 96%-99%) for samples collected within 60 days (n = 243) and 99% (95% CI: 94%-99.9%) for samples within 30 days (n = 119). Specificity for MRSA nares collected 60 days prior to admission (96%, 95% CI: 93-98) and 30 days (96%, 95% CI: 91%-99%) were both high. PPV and sensitivity were lower. Risk factors for MRSA pneumonia were similar.Conclusion and RelevanceMRSA nares screening within 60 days of intensive care unit admission has a high NPV and specificity for MRSA pneumonia in critically ill patients and may be a powerful stewardship tool for avoidance of empirical anti-MRSA therapy.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-07T05:46:24Z
      DOI: 10.1177/10600280211023209
       
  • Dosing Considerations for Combination Antistaphylococcal β-Lactam and
           Glyco/lipopeptide Salvage Therapy for Resistant Gram-Positive Infections:
           A Systematic Review

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      Authors: Justin P. Reinert, Matthew Brown, Reginald Ofori
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:The objective of this systematic review is to evaluate dosing regimens of combination salvage regimens used as part of infectious disease pharmacotherapy.Data Sources:A systematic review was conducted on PubMed, MEDLINE, Scopus, ProQuest Central, and CINAHL through March 2021 using the following terminology: “combination” OR “Seesaw” OR “see-saw” OR “salvage” AND “infection” OR “resistant infection” OR “Gram-positive” AND “beta-lactam” OR “cephalosporin” OR “carbapenem” OR “monobactam” OR “glycopeptide” OR “lipopeptide.”Study Selection and Data Extraction:Following the application of inclusion and exclusion criteria, 8 pieces of literature were ultimately included in this review.Data Synthesis:Vancomycin in combination with another agent was most commonly prescribed as initial or empirical therapy. The most common combination salvage therapy regimen consisted of daptomycin in doses up to 12 mg/kg IV every 24 hours with ceftaroline 200 to 600 mg IV every 8 to 12 hours. Although the duration of combination salvage therapy varied drastically, blood culture clearance was typically observed within 24 hours.Relevance to Patient Care and Clinical Practice:Antimicrobial-resistant Gram-positive organisms have posed an emergent threat to antimicrobial stewardship initiatives. Utilizing either a glycopeptide or lipopeptide antibiotic in combination with an antistaphylococcal β-lactam antibiotic has demonstrated efficacy in treating resistant bacteria. This work describes the heterogeneity of dosing regimens and seeks to define an optimal dose, duration, and combination of antibiotics.Conclusions:Combination salvage therapy has demonstrated efficacy and safety in treatment of resistant Gram-positive infections. It appears the combination of daptomycin and ceftaroline can clear resistant infections expeditiously.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-05T05:50:35Z
      DOI: 10.1177/10600280211021421
       
  • Amantadine and Fatal Events in Patients With Chronic Kidney Disease:
           Analysis of the Japanese Adverse Event Report Database

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      Authors: Satoru Mitsuboshi, Ryohei Kaseda, Ichiei Narita
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-04T10:16:32Z
      DOI: 10.1177/10600280211022439
       
  • Impact of Interferons and Biological Drug Inhibitors of IL-2 and IL-6 on
           Small-Molecule Drug Metabolism Through the Cytochrome P450 System

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      Authors: C. Michael White, Dakota J. Sicignano, Kimberly Smith
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:Assess the impact of interferons and interleukin (IL)-2 and IL-6 inhibitors on cytochrome P450 (CYP) drug metabolism in human subjects.Data Sources:PubMed search from 1980 to March 31, 2021, limited to human subjects and English language via search strategy: (biological drug names) [AND] (cytochrome [OR] CYP metabolism).Study Selection and Data Extraction:Narrative review of human studies assessing biological drugs in select classes that affect CYP drug metabolism.Data Synthesis:Exogenous interferons suppress CYP1A2 (theophylline, caffeine, antipyrone) clearance by 20% to 49% in patients; have minimal impact on CYP3A4 (midazolam and dapsone), CYP2C9 (tolbutamide), or CYP2C19 (mephenytoin) metabolism; and increase CYP2D6 (debrisoquine, dextromethorphan) metabolism. Biological IL-2 inhibitors (basiliximab, daclizumab) have no effect on metabolism via CYP1A2 (caffeine), CYP2C9 (s-warfarin), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), and CYP3A4 (midazolam, tacrolimus) but may enhance CYP3A4 (cyclosporin) metabolism over time. IL-6 inhibitors (sirukumab, tocilizumab, sarilumab) significantly enhance metabolism via CYP2C9 (s-warfarin), CYP2C19 (omeprazole), and CYP3A4 (simvastatin, midazolam) and reduce metabolism via CYP1A2 (caffeine).Relevance to Patient Care and Clinical Practice:Patients using interferons, IL-2, or IL-6 blocking drugs at steady state with CYP substrates could have altered drug metabolism and experience adverse events. With interferons and biological anti-inflammatory drugs, some isoenzymes will be inhibited, whereas others will be enhanced, and the magnitude of the effect can sometimes be significant. In clinical practice, clinicians may consider these metabolic changes as an additive effect to a patient’s entire disease and medication profile when determining risk/benefit of treatment.Conclusions:Interferon therapy or inflammatory suppression via IL-2 or IL-6 can alter steady-state concentrations of CYP-metabolized small-molecule drugs.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-03T04:50:31Z
      DOI: 10.1177/10600280211022281
       
  • Beyond the Guidelines: Treatment of Allergic Bronchopulmonary
           Aspergillosis in Cystic Fibrosis

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      Authors: Madeline G. Tompkins, Rebecca Pettit
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review the available literature addressing alternative allergic bronchopulmonary aspergillosis (ABPA) treatment options for patients with cystic fibrosis (CF).Data Sources:A literature search of PubMed was performed (January 2002 to April 2021) using the following search terms: allergic bronchopulmonary aspergillosis, aspergillus-related lung disease, cystic fibrosis. Manufacturer prescribing information, clinical practice guidelines, and data from ClinicalTrials.gov were incorporated in the reviewed data.Study Selection and Data Extraction:Relevant English-language studies or those conducted in humans were considered for inclusion.Data Synthesis:Available literature for alternative ABPA treatments in CF is lacking randomized controlled trials, but there is considerable support in case reports and case series describing the benefits in pediatric and adult patients. Recent literature has begun to explore the place in therapy for novel, corticosteroid-sparing treatment approaches. The alternative therapies summarized in this review all resulted in clinical improvement and subsequent discontinuation or dose reductions of oral corticosteroids, with minimal reported adverse drug effects.Relevance to Patient Care and Clinical Practice:Although corticosteroids are the cornerstone of ABPA management, the toxicities can be significant limitations in an already high-risk patient population. Patients may fail or become intolerant to guideline-recommended therapies and require alternative treatment approaches.Conclusions:Alternative treatment modalities for ABPA in patients with CF, including azole antifungals, pulsed intravenous glucocorticoids, omalizumab, mepolizumab, and inhaled amphotericin, appear to be efficacious and well tolerated. Pharmacological properties including route of administration, storage and stability, beyond use dating, and adverse effects of the various treatment modalities must be considered when selecting a practical care plan for patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-03T04:49:11Z
      DOI: 10.1177/10600280211022065
       
  • Review of the Efficacy and Safety of Lemborexant, a Dual Receptor Orexin
           Antagonist (DORA), in the Treatment of Adults With Insomnia Disorder

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      Authors: Kristin Waters
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo provide an overview of the efficacy and safety of lemborexant in the treatment of insomnia disorder by assessing the currently available literature.Data SourcesA literature search of PubMed was performed (2010 to March 2021) using the following search terms: lemborexant, sleep, orexinStudy Selection and Data ExtractionAll relevant English-language studies were reviewed and considered, with a focus on phase 3 trials.Data SynthesisThe efficacy and safety of lemborexant in the treatment of insomnia disorder in adults was demonstrated in 2 phase 3 trials. Lemborexant significantly reduced latency to persistent sleep compared with placebo. The first study also demonstrated a significant reduction compared with the active control zolpidem ER. Somnolence and headache were relatively common, but the marked adverse effects associated with other medications commonly used to treat insomnia, such as cognitive and psychomotor impairment and complex sleep-related behaviors, were not observed.Relevance to Patient Care and Clinical PracticeAlthough nonpharmacological therapy is considered first-line treatment for insomnia disorder, pharmacological treatment is most commonly utilized. Lemborexant is a viable pharmacological treatment option for patients who are unable to tolerate the adverse effects associated with the most commonly prescribed medications for insomnia, such as benzodiazepines and sedative-hypnotics (Z drugs). This is especially true for geriatric patients, who may be more sensitive to these adverse effects.ConclusionLemborexant can be recommended to treat insomnia disorder when pharmacological treatment is warranted. It has demonstrated efficacy in clinical trials and is likely better tolerated than most currently available treatment options.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-03T04:46:56Z
      DOI: 10.1177/10600280211008492
       
  • Sedation Usage in COVID-19 Acute Respiratory Distress Syndrome: A
           Multicenter Study

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      Authors: Natalie Tapaskar, Daniel Colon Hidalgo, Grace Koo, Krupa Shingada, Swathi Rao, Raul Rodriguez, Daniel Alcantar, Diana Espinoza Barrera, Raymond Lee, Naveen Rameshkumar, Mukarram Amine, Shelden Rodrigues, Fanny Giron, Akshata Chaugule, Megan A. Rech
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundPatients with COVID-19 acute respiratory distress syndrome (ARDS) have been shown to have high sedation requirements.ObjectiveThe purpose of this study was to compare sedative use between patients with COVID-19 ARDS and non-COVID-19 ARDS.MethodsThis was a retrospective study of patients with COVID-19 ARDS compared with historical controls of non-COVID-19 ARDS who were admitted to 2 hospitals from March 1, 2020, to April 30, 2020, and April 1, 2018, to December 31, 2019, respectively. The primary outcome was median cumulative dose of propofol (µg/kg) at 24 hours after intubation.ResultsThere were 92 patients with COVID-19 ARDS and 37 patients with non-COVID-19 ARDS included. Within the first 24 hours of intubation, patients with COVID-19 ARDS required higher total median doses of propofol: 51 045 µg/kg (interquartile range, 26 150-62 365 µg/kg) versus 33 350 µg/kg (9632-51 455 µg/kg; P = 0.004). COVID-19 patients were more likely receive intravenous lorazepam (37% vs 14%; P = 0.02) and higher cumulative median doses of midazolam by days 5 (14 vs 4 mg; P = 0.04) and 7 of intubation (89 vs 4 mg; P = 0.03) to achieve the same median Richmond Analgesia-Sedation Scale scores. COVID-19 ARDS patients required more ventilator days (10 vs 6 days; P = 0.02). There was no difference in 30-day mortality.Conclusion and RelevancePatients with COVID-19 ARDS required higher doses of propofol and benzodiazepines than patients with non-COVID-19 ARDS to achieve the same median levels of sedation.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-06-02T09:24:04Z
      DOI: 10.1177/10600280211021925
       
  • New Drug Formulary Management and Utilization: Evidence in Sex, Race, and
           Ethnicity: 2019-2020

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      Authors: Christopher A. Keeys, Benjamin W. Harding, Gina E. Migneco, Sina S. Rahini, Hope B. Coleman
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundIt is well established that females and persons of racial and ethnic minorities are frequently underrepresented in clinical trials. These disparities are potentially important aspects of evidence-based formulary management and drug utilization review (DUR) processes.ObjectiveThe purpose of this study was to review the demographic composition of pivotal trials and post-approval study requirements for recent FDA-approved drugs, analyzing the representation of minority groups and its generalizability to the US population or corresponding disease state.MethodsDrugs approved between July 2019 and June 2020 were identified and demographic data including race, ethnicity, and sex was extracted from their pivotal trials. Demographic data was compared to US demographics and/or the disease state demographics for the respective approved drug.ResultsThere were a total of 85 drugs and 142 pivotal trials included in the study. Compared to the estimated US population, the minority groups with a statistically significant underrepresentation across all pivotal trials included Black or African Americans and American Indian or Alaska Natives. The Hispanic/Latinx population had a statistically significant underrepresentation in 55.4% of trials. Females had a statistically significant underrepresentation in 21.2% of trials when compared to the disease state demographics of the respective approved drug.Conclusion and RelevancePersons of minorities are underrepresented in the generation of evidence of safety and efficacy for many new drugs. Formulary management and DUR offer an integrated strategic opportunity for the clinical community to formally and carefully consider the data on sex, race, and ethnicity to address disparities in health care.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-29T06:05:13Z
      DOI: 10.1177/10600280211019765
       
  • Pharmacist-Managed Helicobacter pylori Treatment Service Within a
           Gastroenterology Clinic: Workflow and Real-World Experiences

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      Authors: Shubha Bhat, David Nunes
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundTreatment eradication rates of Helicobacter pylori, a gastrointestinal infection, are 70% to 90% in clinical studies but lower in real-world settings. Potential barriers include multidrug regimen complexity or prescribing/administration errors. A pharmacist-managed H pylori treatment service was implemented to address these barriers and optimize treatment outcomes. The clinical pharmacist provided 2 services: (1) treatment education and monitoring for treatment-naïve patients and (2) treatment initiation, education, and monitoring for treatment-experienced patients.ObjectiveWe aimed to evaluate the impact of a pharmacist-managed H pylori treatment service within a gastroenterology clinic.MethodsWe conducted a retrospective observational cohort study of all patients referred to and seen in the pharmacist-managed H pylori treatment service from July 10, 2019, to December 31, 2020. Patient demographics, prior treatment history, course(s) of treatment prescribed, frequency of follow-ups, and outcomes posttreatment were collected.ResultsThe clinical pharmacist managed 60 referrals for 55 unique patients over a mean of 5 ± 2 visits. Five patients failed H pylori treatment and were re-referred. Identified barriers included prescribing/dispensing and administration errors. Posttreatment, 38 referrals tested for H pylori eradication, of which 100% of treatment-naïve patients and 69% of treatment-experienced patients were cured, and 13 (22%) referrals were lost to follow-up.Conclusion and RelevanceThis study described and assessed the impact of a pharmacist-managed H pylori treatment service in a gastroenterology clinic, in which various barriers were effectively addressed to optimize treatment outcomes. Future studies should focus on long-term outcome, impact on health care costs, and patient satisfaction with this service.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-29T06:05:04Z
      DOI: 10.1177/10600280211021501
       
  • Call to Pharmacists: End Use of “Red Man Syndrome”

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      Authors: Christina G. Rivera, Keenan L. Ryan
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Red Man Syndrome is a term used for an adverse event attributed to vancomycin infusion. Based on the presentation within white patients, the term is imprecise at best and can lead to suboptimal classification and management. Recent calls have advocated for the discontinuation of the use of this terminology. Pharmacists should take the lead in advocating for this change.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-29T06:04:55Z
      DOI: 10.1177/10600280211021417
       
  • Evaluation of Serum Sodium Correction Rates for Management of Hyponatremia
           in Hospitalized Patients

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      Authors: Christine T. Pham, Hagar S. Kassab, Jackie P. Johnston
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Appropriate correction of hyponatremia can reduce complications such as osmotic demyelination syndrome (ODS).Objective:To evaluate rates of serum sodium correction in hyponatremic hospitalized patients and identify factors associated with higher rates of overcorrection.Methods:This is an institutional review board–approved single-center, retrospective chart review of patients ≥18 years of age with at least 1 serum sodium
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-22T10:41:28Z
      DOI: 10.1177/10600280211019752
       
  • Response to Comment on “Expectation for Prediction Models for
           Prothrombin Time International Normalized Ratio Under Warfarinization for
           Safety Use in the Era of Precision Medicine”

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      Authors: Tatsuya Yagi
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-21T10:08:33Z
      DOI: 10.1177/10600280211018786
       
  • Comment: Association Between the Prothrombin Time-International Normalized
           Ratio and Concomitant Use of Antibiotics in Warfarin Users: Focus on Type
           of Antibiotic and Susceptibility of Bacteroides fragilis to Antibiotics

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      Authors: Satoshi Takanashi
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-20T10:47:37Z
      DOI: 10.1177/10600280211018804
       
  • Zonisamide Use With Continuous Renal Replacement Therapy

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      Authors: Cassandra J. Schmitt, Erin D. Wieruszewski, Patrick M. Wieruszewski
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-19T10:49:57Z
      DOI: 10.1177/10600280211017167
       
  • Deferasirox-Induced Hyperammonemia in an Adult Patient After Allogeneic
           Stem Cell Transplantation

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      Authors: Atakan Turgutkaya, Ali Zahit Bolaman, İrfan Yavaşoğlu
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-19T10:48:55Z
      DOI: 10.1177/10600280211016960
       
  • Use of Capsaicin Cream in Cannabinoid Hyperemesis Syndrome in Patients
           Presenting to the Emergency Department

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      Authors: Allison Lee, Zlatan Coralic
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundCannabinoid hyperemesis syndrome (CHS) is characterized by cyclical nausea, vomiting, and abdominal pain often relieved with hot showers. Patients with CHS are usually long-term cannabis smokers whose symptoms are not relieved by antiemetics. The use of topical capsaicin has been recently reported as an adjunctive therapy in the emergency department (ED).ObjectiveTo describe the use of capsaicin cream in patients presenting to the ED with suspected CHS.MethodsWe performed a retrospective review of patients with suspected CHS receiving capsaicin in an ED from July 2014 to October 2018. We report data on demographics, cannabis consumption, hot showers use, length of stay, concurrent treatments, pain scores, and adverse events.ResultsThere were 57 patients who received capsaicin cream for suspected CHS. Nearly all patients received antiemetics (98%), whereas 47% of patients received an opioid. Antiemetics were typically administered first (median, 1.6 hours; interquartile range [IQR], 0.9-2.4]), followed by an opioid (median, 1.8 hours [IQR, 1-3.75]), followed by capsaicin cream (median 4 hours [IQR, 2.7-5.2]). The overall precapsaicin pain score was 8 (IQR, 2-9), decreasing to 5.5 (IQR, 0-8). Around 42% of patients received no further symptomatic therapy after capsaicin. No adverse drug events to capsaicin were reported.Conclusion and RelevanceThis is the largest retrospective study describing capsaicin cream use in suspected CHS patients with a focus on abdominal pain relief. Capsaicin treatment was associated with a modest pain score reduction. Application of these findings may help providers in identifying more effective therapies to provide symptomatic relief for CHS patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-17T09:46:56Z
      DOI: 10.1177/10600280211018516
       
  • An Evaluation of the Effect of Catheter-Directed Continuous Infusion of
           Local Anesthetic by Elastomeric Pump on Opioid Usage Following Donor
           Kidney Nephrectomy

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      Authors: Jessica Goldsby, Kerry Schwarz, Ike Kim, Victor Lewis, Clark Lyda
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundPostoperative pain management following donor nephrectomy can prove challenging for immediate discharge on postoperative day 1 or 2. Although the standard for pain control is utilization of opioids, this increases the risk of postoperative ileus and, if continued inappropriately, increases excess opioids circulating in the community. One strategy that proposes to limit postoperative opioids in kidney donors is the continuous infusion of local anesthetics (CILA), though the effect on patient outcomes is unclear.ObjectiveThe purpose of this study was to evaluate the effectiveness of postoperative CILA to decrease opioid usage in kidney donors who undergo laparoscopic nephrectomy.MethodsA retrospective analysis was conducted of kidney donors who underwent laparoscopic nephrectomy and received CILA (CILA group) compared with kidney donors who received standard-of-care (SOC) postoperative analgesia. The primary outcome was the mean total oral morphine equivalents (OMEs) administered following surgery.ResultsA total of 176 kidney donors were evaluated, 88 in each group. The mean OME administered in the CILA group was significantly higher than in the SOC group: 194.8 versus 133.5 mg (P = 0.003). Mean total postoperative administration of acetaminophen was also increased in the CILA group: 3736.9 versus 2611.6 mg (P = 0.0041). Mean length of stay following surgery was higher in the kidney donors who received CILA, whereas return to bowel function, time to ambulation, and pain scores were not significantly different.Conclusion and RelevanceThis report demonstrated that CILA is not an effective modality to reduce opioid utilization or improve recovery in kidney donors following laparoscopic nephrectomy.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-17T09:45:13Z
      DOI: 10.1177/10600280211017894
       
  • Impact of Opioid Administration in the Intensive Care Unit and Subsequent
           Use in Opioid-Naïve Patients

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      Authors: Niki M. Krancevich, Julie J. Belfer, Heather M. Draper, Kyle J. Schmidt
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundOpioids are a mainstay of therapy for patients in the intensive care unit (ICU) as part of the analgesia-first approach to sedation. Despite knowledge of acute consequences of opioid based analgosedation, less is known about the potential long-term consequences, including the effect of opioid administration in the ICU on subsequent opioid use in opioid-naïve patients.ObjectiveTo evaluate the relationship between ICU opioid administration to opioid-naïve patients and subsequent opioid use following discharge.MethodsA query of the electronic medical record was performed to identify opioid-naïve adult patients admitted directly to an ICU. Patients who received continuous intravenous infusion of fentanyl, hydromorphone, or morphine were screened for inclusion into the analysis.ResultsOf the 342 patients included for analysis, 164 (47.1%) received an opioid at hospital discharge. In total, 17 of the 342 patients (5.0%) became long-term users, noted to be more common in patients who received an opioid prescription at discharge (8.7% vs 1.6%; P = 0.006). Neither total ICU morphine milligram equivalent (MME) nor average daily ICU MME administration were found to correlate with daily MME prescription quantity at discharge (R2 = 0.008 and R2 = 0.03, respectively). Following control for potentially confounding variables, total ICU MME administration remained an insignificant predictor of subsequent receipt of an opioid prescription at discharge and long-term opioid use.Conclusion and RelevanceThis study failed to find a significant relationship between ICU opioid use in opioid-naïve patients and subsequent opioid use. These findings highlight the need to focus on transitions points between the ICU and discharge as potential opportunities to reduce inappropriate opioid continuation.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-17T09:43:25Z
      DOI: 10.1177/10600280211016856
       
  • Oriahnn: New Drug Approved for Treating Heavy Menstrual Bleeding in Women
           With Uterine Fibroids

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      Authors: Sarah E. Lynch, Danielle C. Mayer
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      ObjectiveTo review data of elagolix plus estradiol and norethindrone acetate as add-back therapy for the treatment of heavy menstrual bleeding (HMB) in premenopausal women with uterine fibroids.Data SourcesLiterature search of PubMed/MEDLINE and SCOPUS was performed using the search terms Oriahnn; elagolix, estradiol, norethindrone AND heavy menstrual bleeding; elagolix AND heavy menstrual bleeding; and gonadotropin-releasing hormone receptor antagonist AND heavy menstrual bleeding between January 1, 1996, to March 2, 2021. Additional data were obtained from prescribing information, references of identified articles, and abstracts from scientific meetings.Study Selection/Data ExtractionClinical trials and articles discussing elagolix plus add-back therapy for the management of HMB in women with leiomyomas were included.Data SynthesisPhase 3 trials met the primary end point of menstrual blood loss (MBL) less than 80 mL at month 6 and at least a 50% reduction in MBL from baseline to the final month in 68.5% of women taking elagolix plus add-back therapy enrolled in UF-1 (8.7% placebo) and 76.5% of women in UF-2 (10% placebo). The most common adverse effects include hot flushes, nausea, headache, and night sweats.Relevance to Patient Care and Clinical PracticeWomen with symptomatic uterine fibroids can experience significant HMB resulting in distress, depression, and anxiety. Surgical intervention remains the most commonly recommended and chosen treatment. Elagolix plus add-back therapy is a nonsurgical, oral option.ConclusionsElagolix plus add-back therapy is effective in reducing menstrual bleeding associated with uterine fibroids. However, there are several warnings and precautions that must be considered.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-17T09:40:40Z
      DOI: 10.1177/10600280211015987
       
  • The Safety of Continuous Infusion Propofol in Mechanically Ventilated
           Adults With Coronavirus Disease 2019

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      Authors: Corey J. Witenko, Audrey J. Littlefield, Sajjad Abedian, Anjile An, Philip S. Barie, Karen Berger
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Propofol is commonly used to achieve ventilator synchrony in critically ill patients with coronavirus disease 2019 (COVID-19), yet its safety in this patient population is unknown.Objective:To evaluate the safety, in particular the incidence of hypertriglyceridemia, of continuous infusion propofol in patients with COVID-19.Methods:This was a retrospective study at 1 academic medical center and 1 affiliated teaching hospital in New York City. Adult, critically ill patients with COVID-19 who received continuous infusion propofol were included. Patients who received propofol for
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-14T07:22:46Z
      DOI: 10.1177/10600280211017315
       
  • Advice Provided by a Pharmacy Residency Research Committee

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      Authors: Erin R. Weeda, Genevieve L. Hayes, Eleni A. Gaspar, Rory J. Thomas, Jean M. Nappi, Kyle A. Weant
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-13T04:56:44Z
      DOI: 10.1177/10600280211017332
       
  • Deviant Dosing: A Post hoc Analysis of Pharmacist Characteristics Related
           to Renal Dosing Decisions

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      Authors: Sean M. McConachie, Claudia M. Hanni, Sheila M. Wilhelm
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundA recent study demonstrated that pharmacists presented with multiple estimating equations deviated from recommended dosing guidance more often than pharmacists who were presented with a single estimate on clinical vignettes.ObjectivesTo identify characteristics associated with an increased tendency to deviate from approved recommendations.MethodsParticipant data were split into 2 cohorts: pharmacists who chose a dose that was inconsistent with dosing recommendations on at least 1 of the 4 vignettes and pharmacists who did not deviate on a single case. Bivariate analysis of demographic- and practice-related variables were conducted between groups using the χ2, Mann-Whitney U, or Student t-test for nominal, ordinal, and continuous variables, respectively. Statistically different covariates between groups (P < 0.05) were assessed using multivariable linear regression.ResultsSurvey data from 154 inpatient pharmacists, 71 of whom deviated on at least 1 clinical vignette, were analyzed. On univariate analysis, deviator pharmacists were more likely to have completed postgraduate residency training (68% vs 41%; P < 0.05) and board certification (39% vs 20%; P < 0.05). Deviator pharmacists were also more likely to have been presented with multiple renal estimates as opposed to a single estimate and had differing renal dosing practices at baseline (P < 0.05). Following multivariable regression, residency training, mismatched baseline renal practices, and multiple renal estimates remained independent predictors (P < 0.05) of dosing deviation.Conclusion and RelevanceHigher clinical training, practice variation, and multiple renal estimates may affect renal dosing practices. Prospective, statistically powered studies are needed to verify these hypotheses.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-08T10:36:23Z
      DOI: 10.1177/10600280211016328
       
  • Assessment and Impact of Intravenous Medication Fluid Administration in
           Critically Ill Patients With Acute Respiratory Failure

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      Authors: Jeffrey P. Gonzales, Debbi Child, Thelma Harrington, Peter Kratz, Laura Seiberlich, Giora Netzer, Carl B. Shanholtz
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Positive fluid balance early in critical illness is associated with poor outcomes. Reducing intravenous medication volume may mitigate volume overload. Objective: Assessment of fluid and medication administration and clinical outcomes in acute respiratory failure.Methods:Single-center, prospective observational study of hemodynamically stable adult patients in a medical intensive care unit (MICU) with acute respiratory failure.Results:Median cumulative total intake volume was 12 890 (interquartile range [IQR] = 8654-22 221) mL (n = 27), and median cumulative intravenous medication volume was 3563 (IQR = 2371-9412) mL over the first 7 days. Medication volume accounted for 27.6% of aggregate fluid volume. Median daily intravenous medication volume administered was 591 (IQR = 339-1082) mL. Cumulative fluid volume was associated with reduced ventilator-free days (r2 = −0.393; P = 0.043), and cumulative fluid volumes during the first 3 and 7 days were associated with increased MICU length of stay (LOS ± standard error 0.73 ± 0.35 d/L, P = 0.047, and 0.38 ± 0.16 d/L, P = 0.021, respectively). Cumulative medication volume administered significantly reduced the likelihood of mechanical ventilator liberation (hazard ratio [HR] = 0.917; 95% CI: 0.854, 0.984; P = 0.016) and MICU discharge (HR = 0.911; 95% CI: 0.843, 0.985; P = 0.019). Small-volume infusion may decrease cumulative intravenous medication volume by 38%.Conclusion and Relevance:Intravenous medication diluent contributes substantially to total fluid intake in patients with acute respiratory failure and is associated with poor outcomes. Reduction of intravenous medication fluid volume to improve clinical outcomes should be further investigated.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-05-05T11:34:44Z
      DOI: 10.1177/10600280211013581
       
  • Effect of PARP Inhibitors as Maintenance Treatment on Restricted Mean
           Survival Time in Platinum-Sensitive Recurrent Ovarian Cancer: A Systematic
           Review and Meta-analysis

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      Authors: Masayuki Kaneko
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundEarlier trials on the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors in platinum-sensitive relapsed ovarian cancer used the hazard ratio (HR) as an efficacy parameter.ObjectiveThe present meta-analysis was focused on improving the robustness and clinical interpretability of the efficacy evaluation of PARP inhibitors using the restricted mean survival time (RMST).MethodsA search for relevant studies published up to July 31, 2020, was performed in electronic databases to identify eligible trials comparing PARP inhibitors with placebo. The difference in RMST was used as a PARP inhibitor efficacy parameter. Combined differences in RMST with 95% CIs across studies were calculated using a random-effects model.ResultsFour trials (6 articles) were assessed, including 1079 patients treated with PARP inhibitors and 598 with placebo. The combined RMST differences for up to 360 days (PARP inhibitors minus placebo: point estimate and 95% CI) among all patients and the patients of subgroups with BRCA mutations, homologous recombination-deficient (HRD) carcinoma, and BRCA wild-type carcinoma were 87 days (95% CI = 71, 102), 112 days (95% CI = 96, 129), 99 days (95% CI = 80, 119), and 69 days (95% CI = 47, 92), respectively. The combined RMST differences for up to 660 and 720 days were also larger among patients with BRCA mutations than among those with HRD carcinoma.Conclusion and RelevanceBased on using the RMST difference as an alternative measure to the HR, this meta-analysis suggests that PARP inhibitors are the most effective for patients with BRCA mutations, followed by patients with HRD carcinoma.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-30T06:49:23Z
      DOI: 10.1177/10600280211013489
       
  • The Safety and Efficacy Evaluation of Dexmedetomidine for Procedural
           Sedation and Postoperative Behaviors in Pediatric Populations: A
           Systematic Review and Meta-analysis

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      Authors: Linguang Gan, Xiaohong Zhao, Xiangjian Chen
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:This study systematically evaluated the safety and efficacy of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population as well as whether the results met the information required to draw conclusions.Objective:To evaluate the safety and efficacy evaluation of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population.Methods:PubMed, Cochrane library, Web of Science and Ovid MEDLINE were searched to obtain randomized controlled trials (RCTs) comparing dexmedetomidine with control medicine and comparing different doses of dexmedetomidine.Results:There were a total of 16 RCTs for a total of 3240 patients. Dexmedetomidine slowed down the heart rate (HR; mean difference: −13.27; 95% CI: −16.41 to 10.14; P < 0.001) and reduced postoperative delirium (risk ratio [RR]: 0.31; 95% CI: 0.20-0.50; P < 0.001), the number of pain patients (RR: 0.48; 95% CI: 0.30-0.75; P = 0.002), and desaturation (RR: 0.34; 95% CI: 0.13-0.89; P = 0.03) compared with the control group. The limitation was that it was difficult to determine the range of low- and high-dose dexmedetomidine.Conclusion and Relevance:Dexmedetomidine slowed down intraoperative HR within the normal range, which might reduce myocardial oxygen consumption. It reduced postoperative pain and postoperative complications: delirium and desaturation. Dexmedetomidine showed no dose-dependent increase in the procedural sedation time of pediatric patients. Clinically, dexmedetomidine can improve pediatric procedural sedation and postoperative behavior, and it can be considered as a related medicine for safety in pediatric surgery.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-29T11:14:55Z
      DOI: 10.1177/10600280211009845
       
  • Antibody-Mediated Rejection Management Following Lung Transplantation

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      Authors: Kristen Neuhaus, Benjamin Hohlfelder, Jessica Bollinger, Marcus Haug, Heather Torbic
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundAlthough antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited.ObjectiveThe purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients.MethodsThis single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019.ResultsA total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter.Conclusion and RelevanceThis represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-26T09:17:16Z
      DOI: 10.1177/10600280211012410
       
  • Approach to Sedation and Analgesia in COVID-19 Patients on Venovenous
           Extracorporeal Membrane Oxygenation

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      Authors: Diane Dreucean, Jesse E. Harris, Prakruthi Voore, Kevin R. Donahue
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To describe clinically pertinent challenges of managing sedation in COVID-19 patients on venovenous extracorporeal membrane oxygenation (VV-ECMO) and describe considerations for enhanced safety and efficacy of pharmacological agents used.Data Sources:A PubMed search was performed using the following search terms: ECMO, ARDS, sedation, COVID-19, coronavirus, opioids, analgesia, fentanyl, hydromorphone, morphine, oxycodone, methadone, ketamine, propofol, dexmedetomidine, clonidine, benzodiazepines, midazolam, lorazepam, and diazepam.Study Selection and Data Extraction:Relevant clinical and pharmacokinetic studies were considered. All studies included were published between January 1988 and March 2021.Data Synthesis:Patients with acute respiratory distress syndrome secondary to COVID-19 may progress to requiring VV-ECMO support. Agents frequently used for sedation and analgesia in these patients have been shown to have significant adsorption to ECMO circuitry, leading to possible diminished clinical efficacy. Use of hydromorphone-based analgesia has been associated with improved clinical outcomes in patients on VV-ECMO. However, safety and efficacy regarding use of other agents in this patient population remains an area of further research.Relevance to Patient Care and Clinical Practice:This review addresses clinical challenges associated with sedation management in COVID-19 patients requiring VV-ECMO support and provides potential strategies to overcome these challenges.Conclusions:Historically, sedation and analgesia management in patients requiring ECMO support have posed a challenge for bedside clinicians given the unique physiological and pharmacokinetic changes in this patient population. A multimodal strategy to managing analgesia and sedation should be used, and the use of enteral agents may play a role in reducing parenteral agent requirements.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-22T08:53:39Z
      DOI: 10.1177/10600280211010751
       
  • Payer-Directed Infusion Site Strategies Negatively Affect Outcomes in
           Patients With Inflammatory Bowel Disease

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      Authors: David Choi, Itishree Trivedi
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-17T08:57:07Z
      DOI: 10.1177/10600280211010527
       
  • Impact of Removing the Race Coefficient in Renal Function Estimate
           Equations on Drug Dosage Recommendations

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      Authors: Janine Miller, John P. Knorr
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundThe appropriateness of including the race coefficient in glomerular filtration rate (GFR) equations in Black patients is debated, and the impact on drug dosing is unknown.ObjectiveThis study explored the impact of removing the race coefficient on drug dosing in Black patients in comparison to conventional methods.MethodsThis was a retrospective study of hospitalized patients who self-identified as Black/African American and were prescribed an antimicrobial that includes renal dosage recommendations in the product labeling. The primary end point was the discordance between drug dosing recommendations derived by body surface area deindexed GFR estimated by the CKD-EPI equation (Chronic Kidney Disease Epidemiology study) with and without race versus recommendations derived from Cockcroft-Gault (CG).ResultsA total of 210 Black patients were included. There was an 18% rate of discordance when GFR was estimated with the race coefficient (GFR w/Race) versus without the race coefficient (GFR w/out Race). GFR w/out Race had a higher level of agreement with dosing by creatinine clearance (CrCl; κ = 0.779) than GFR w/Race versus CrCl (κ = 0.651). GFR w/out Race had less within-patient difference than GFR w/Race in comparison to CrCl (mean difference: −6.3 vs −18.0 mL/min).Conclusions and RelevanceThis represents the first report to examine the removal of the race coefficient and its implication on drug dose discordance. GFR w/out Race had a higher level of agreement and less drug dose discordance than GFR w/Race, in comparison to CrCl estimates. If GFR equations are considered comparable to CrCl for the purposes of guiding drug dosing, GFR w/out Race should be considered.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-17T08:52:23Z
      DOI: 10.1177/10600280211010228
       
  • Development of a Theory-Informed Behavior Change Intervention to Reduce
           Inappropriate Prescribing of Nephrotoxins and Renally Eliminated Drugs

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      Authors: Sandra L. Kane-Gill, Erin F. Barreto, Azra Bihorac, John A. Kellum
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Goals of managing patients with acute kidney injury (AKI) are mitigating disease progression and ensuring safety while providing supportive care because no effective treatment exists. One strategy recommended in guidelines to meet these goals is optimizing medication management. Unfortunately, guideline implementation appears to be lacking as observed by the frequent occurrence of medication errors and adverse drug events.Objective:To address this performance gap in the care of hospitalized patients receiving nephrotoxins and renally eliminated drugs, we sought to provide a potential intervention based on theory-informed behavior change.Methods:Formative research with a qualitative analysis identifying what needs to change in patient care was completed by obtaining clinician opinion and expert opinion and reviewing the published literature. Frontline providers, including 8 physicians, 4 pharmacists, and a multiprofessional group of authors, provided insight into possible barriers to appropriate prescribing. Capability, Opportunity, Motivation and Behavior model and Theoretical Domain Framework were applied to characterize behavior change interventions and inform a potential implementation intervention for changing inappropriate prescribing behaviors.Results:Lack of knowledge about appropriate drug management in patients at risk for adverse outcomes was provided as a major barrier. Other reported barriers included a lack of: (1) tools to assist with drug management, (2) motivation to make changes, (3) routinization, and (4) an accountable clinician.Conclusions and Relevance:Assigning a designated clinician to execute a stepwise, routine care process following the checklist provided is a recommended intervention to overcome barriers. The intended impact is behavior change that reduces inappropriate prescribing.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-15T09:34:39Z
      DOI: 10.1177/10600280211009567
       
  • Factor VIII Inhibitor Bypassing Activity (FEIBA) Reversal for Apixaban and
           Rivaroxaban in Patients With Acute Intracranial and Nonintracranial
           Hemorrhage

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      Authors: Aleah R. Hunt, Shawn N. Coffeen, Dane L. Shiltz, Calvin Ice, Jessi Parker
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:The clinical use of factor VIII inhibitor bypassing activity (FEIBA) for factor Xa (FXa) inhibitor reversal is derived from small studies with notable variation in patient eligibility for use, dosage regimens, concurrent supportive care, and outcome measures. Consequently, additional effectiveness and safety data are warranted to expand the literature evaluating FEIBA for FXa inhibitor reversal.Objective:This study sought to determine the incidence of observed effective hemostasis within 24 hours of post-FEIBA® administration as well as in-hospital and 30-day post-discharge incidences of thromboembolic event (TEE) and mortality between apixaban and rivaroxaban in the intracranial hemorrhage (ICH) and non-ICH populations.Methods:This case series evaluated patients between January 1, 2014 through July 1, 2019 who received at least one FEIBA® dose for apixaban or rivaroxaban reversal secondary to acute ICH or non-ICH. Patient demographics, FEIBA® dosages, adjunct treatments, effectiveness, and safety outcomes were retrospectively collected from electronic medical record review. Modified hemostasis outcomes, adapted from criteria previously published by Sarode et al., TEE, and mortality between apixaban and rivaroxaban in the ICH and non-ICH populations were evaluated.Results:Among the 104 patients evaluated, 62 received apixaban and 42 rivaroxaban. Thirty apixaban and 25 rivaroxaban users experienced ICH, whereas 32 apixaban and 17 rivaroxaban users experienced non-ICH. Among the combined ICH and non-ICH populations, effective hemostasis occurred in 89%, TEE in 8%, and mortality in 13%. No statistically significant differences were observed within ICH and non-ICH populations receiving apixaban or rivaroxaban regarding effective hemostasis, TEE, or mortality.Conclusion and Relevance:The combined ICH and non-ICH overall rates of effective hemostasis, TEE, and mortality were comparable to preexisting studies of FEIBA for factor Xa inhibitor reversal. The limitations inherent to the study design warrant a randomized controlled trial with an active comparator to confirm these observations.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-10T09:04:55Z
      DOI: 10.1177/10600280211004583
       
  • Usefulness of the Biomarker TIMP-2•IGFBP7 for Acute Kidney Injury
           Assessment in Critically Ill Patients: A Narrative Review

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      Authors: Brian L. Erstad
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objectives:To review the clinical usefulness of the biomarker TIMP-2•IGFBP7 in adult, general medical-surgical intensive care unit (ICU) settings.Data Sources:PubMed (1946 to mid-February 2021) and EMBASE (1947 to mid-February 2021) with bibliographies of retrieved articles reviewed for additional articles.Study Selection and Data Extraction:Studies evaluating use of the urinary TIMP-2•IGFBP7 assay in adult patients in ICU settings.Data Synthesis:Studies published after investigations leading to TIMP-2•IGFBP7 assay approval confirm the appropriateness of considerations discussed in product labeling, such as use of the test within 12 hours of assessment, use of a dichotomous 0.3 (ng/mL)2/1000 cutoff, and use only in combination with other assessments of acute kidney injury (AKI). However, as a biomarker routinely used for early identification of patients at risk for AKI in mixed ICU populations, the additional resources required for TIMP-2•IGFBP monitoring are difficult to justify because of limited data demonstrating usefulness in preventing or ameliorating AKI and its attendant complications.Relevance to Patient Care and Clinical Practice:Biomarkers are potentially useful not only for assessment and diagnosis of AKI, but also for practitioners involved in the management of nephrotoxic medications and medications needing adjustment for decreased kidney function.Conclusions:Although there is evidence to suggest that the urinary TIMP-2•IGFBP7 biomarker is helpful in predicting AKI progression in general medical-surgical ICU patients when used within 12 hours of patient assessment in combination with routine testing, including serum creatinine and urine output, there is little evidence that its use leads to improvements in clinically important patient outcomes.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-08T11:25:18Z
      DOI: 10.1177/10600280211005425
       
  • Safety and Efficacy of Non–Vitamin K Oral Anticoagulant Use Early After
           Cardiac Surgery: A Systematic Review

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      Authors: Erica H. Z. Wang, Jian Ye, Ricky Turgeon
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To determine the safety and efficacy of non–vitamin K oral anticoagulants (NOACs) initiated early after cardiac surgery.Data Sources::Cochrane Central Register of Controlled Trials, EMBASE, and MEDLINE (database inception to January 20, 2021), www.clinicaltrials.gov, www.who.int/ictrp/search/en/, NOAC trial registries, and bibliographies of relevant guidelines and other reviews were used.Study Selection and Data Extraction:Observational studies and randomized controlled trials (RCTs) that initiated NOACs within the index hospitalization and that reported bleeding for the primary outcome were included.Data Synthesis:A total of 6 cohort studies, 1 RCT, and 3 ongoing RCTs were included. Most studies were single-centered, limited to postoperative atrial fibrillation after coronary artery bypass grafting, and with 30-day follow-up; few studies included patients with isolated bioprosthetic valve replacement or valve repair. Bleeding risk varied (0%-28.6%), and all but one study showed no significantly higher risk with NOAC compared with warfarin.Relevance to Patient Care and Clinical Practice:Overall, NOACs were used in 26% to 37.5% of patients early after cardiac surgery. Starting a NOAC on postoperative day 4 appeared to have similar bleeding rates compared with warfarin, but clinical application is limited by heterogeneity of outcome definitions, confounding, and bias. Compared with warfarin, NOACs may have similar thromboembolism risk, reduced length of stay, and cost.Conclusions:There is limited evidence to guide NOAC use early after cardiac surgery. Three ongoing randomized trials will add to the literature and provide guidance for clinicians on whether, in whom, when, and how to use NOACs safely early after cardiac surgery.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-05T07:39:42Z
      DOI: 10.1177/10600280211006830
       
  • Effect of Vasopressin Dose on Hemodynamic Response in Obese Patients With
           Septic Shock: A Retrospective Observational Study

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      Authors: Casey A. Dubrawka, Kevin D. Betthauser, Hannah E. Pope, Gabrielle A. Gibson
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundNo clear association between standard vasopressin doses and body mass index exists, despite potential pharmacokinetic and pharmacodynamic variability among patients with septic shock. It is unknown if higher doses may alter hemodynamic response.ObjectiveThe purpose of this study was to evaluate the effect of vasopressin dose on hemodynamic response in obese patients with septic shock.MethodsA single-center, retrospective cohort study was conducted in adult, obese patients with septic shock receiving catecholamine vasopressors and vasopressin. Patients were analyzed according to vasopressin dose received: standard dose (≤0.04 U/min) and high dose (>0.04 U/min). The primary outcome was percentage change in norepinephrine equivalent (NEQ) dose.ResultsA total of 182 patients were included in the analysis, with 136 in the standard-dose vasopressin group and 46 in the high-dose vasopressin group. There was no difference in percentage change in NEQ dose at 6 hours after standard- or high-dose vasopressin attainment (−28.6% vs −19.1%; P = 0.166). A greater increase in mean arterial pressure (MAP) at 6 hours was observed with receipt of high-dose vasopressin (23.3% vs 15.3%; P = 0.023). Duration of shock and length of stay were significantly longer in patients who received high-dose vasopressin, with no difference in in-hospital mortality.Conclusion and RelevanceThis represents the first analysis comparing standard and higher doses of vasopressin in obese patients with septic shock. Receipt of high-dose vasopressin was not associated with a difference in catecholamine requirement or improved outcomes. Further studies are warranted to provide guidance on the use of high-dose vasopressin in septic shock.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-03T07:42:47Z
      DOI: 10.1177/10600280211007213
       
  • Complications and Management of Eptifibatide-Induced Thrombocytopenia

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      Authors: Faisal Masood, Saad Hashmi, Adib Chaus, Anna Hertsberg, Eli D. Ehrenpreis
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      BackgroundEptifibatide is used in acute coronary syndromes to reversibly block platelet aggregation by inhibiting the platelet glycoprotein IIb/IIIa receptor. A serious adverse effect of eptifibatide is a profound drop in platelet count, termed eptifibatide-induced thrombocytopenia (EIT).ObjectiveTo provide insight into the types of complications and management of EIT.MethodsCases of EIT submitted to the Food and Drug Administration adverse event reporting system were evaluated. Data analyses included management of EIT, complications of thrombocytopenia, initial platelets, and platelet nadir following eptifibatide.Results103 cases of EIT were reported from January 2010 to 2019; 57 cases met the Naranjo scale and were included. Only 37 of those cases contained information on how EIT was managed. Eptifibatide administration was withheld in all 37 of those cases. Platelet transfusions were administered in 20 cases (54%). Two cases were managed with steroids (5.4%), and 1 case used intravenous immunoglobulin G to reverse EIT (2%). The median initial platelet count prior to administration of eptifibatide was 207 000 cells/mm3 (SD = 69 000; n = 27), and median platelet nadir was 9000 cells/mm3 (SD = 19 000; n = 35) The majority of complications of EIT included bleeding events (16/28, 57%). Delayed procedures, prolonged stay, allergic reactions, and thrombosis were each reported in 3 patients (10.75%).Conclusion and RelevanceMost cases of EIT were managed by withholding eptifibatide with platelet transfusion if necessary. The majority of complications included bleeding. However, significant procedure delays, prolonged hospital stay, thrombosis, and allergic reactions were also reported.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-04-03T07:42:18Z
      DOI: 10.1177/10600280211006645
       
  • Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug
           Associations and Clinical Considerations

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      Authors: Emily Brandl, Zachery Halford, Matthew D. Clark, Chris Herndon
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To provide an overview of clinical recommendations regarding genomic medicine relating to pain management and opioid use disorder.Data Sources:A literature review was conducted using the search terms pain management, pharmacogenomics, pharmacogenetics, pharmacokinetics, pharmacodynamics, and opioids on PubMed (inception to February 1, 2021), CINAHL (2016 through February 1, 2021), and EMBASE (inception through February 1, 2021).Study Selection and Data Extraction:All relevant clinical trials, review articles, package inserts, and guidelines evaluating applicable pharmacogenotypes were considered for inclusion.Data Synthesis:More than 300 Food and Drug Administration–approved medications contain pharmacogenomic information in their labeling. Genetic variability may alter the therapeutic effects of commonly prescribed pain medications. Pharmacogenomic-guided therapy continues to gain traction in clinical practice, but a multitude of barriers to widespread pharmacogenomic implementation exist.Relevance to Patient Care and Clinical Practice:Pain is notoriously difficult to treat given the need to balance safety and efficacy when selecting pharmacotherapy. Pharmacogenomic data can help optimize outcomes for patients with pain. With improved technological advances, more affordable testing, and a better understanding of genomic variants resulting in treatment disparities, pharmacogenomics continues to gain popularity. Unfortunately, despite these and other advancements, pharmacogenomic testing and implementation remain underutilized and misunderstood in clinical care, in part because of a lack of health care professionals trained in assessing and implementing test results.Conclusions:A one-size-fits-all approach to pain management is inadequate and outdated. With increasing genomic data and pharmacogenomic understanding, patient-specific genomic testing offers a comprehensive and personalized treatment alternative worthy of additional research and consideration.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-27T05:23:29Z
      DOI: 10.1177/10600280211003875
       
  • Influence of RFC1 c.80A>G Polymorphism on Methotrexate-Mediated Toxicity
           and Therapeutic Efficacy in Rheumatoid Arthritis: A Meta-analysis

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      Authors: Shaik Mohammad Naushad, Salman A. Alrokayan, Fahad N. Almajhdi, Tajamul Hussain
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Methotrexate (MTX) is an antirheumatic drug, transported by reduced folate carrier-1 (RFC1). The most common RFC1 gene variant, c.80 A>G (rs1051266) is ambiguously linked to adverse effects of MTX therapy in some rheumatoid arthritis (RA) patients.Objective:The purpose of meta-analysis was to summarize all major published studies on c.80 A>G SNP to clarify this ambiguity in MTX therapy.Methods:A total of 18 studies representing 3592 RA patients comprising 699 men and 2893 women were included. Both fixed and random effect models were applied to study the data.Results:The RFC1 80A-allele showed null association with MTX-mediated toxicity in both fixed (odds ratio [OR] = 0.91; 95% CI = 0.80-1.03) and random effects (OR = 0.89; 95% CI: 0.71-1.11) models. Because heterogeneity was observed in this association (P = 0.0006), data were segregated based on use of folate therapy. In 7 studies (n = 1191) where folate was used along with MTX, RFC1 AA patients showed reduced risk for MTX-mediated toxicity (OR = 0.67; 95% CI: 0.50-0.89; P = 0.0006). The RFC1 80A-allele was found to increase the efficacy of MTX therapy by 1.53-fold (95% CI: 1.24-1.88), whereas the 80AA-genotype increased the efficacy by 1.85-fold (95% CI: 1.41-2.42). No publication bias was observed in these associations.Conclusion and Relevance:RFC1 c.80 A>G is an important pharmacogenetic determinant of MTX therapy in RA. The RFC1 80A-allele robustly increased therapeutic efficacy and safety when folate was used along with MTX. Findings are relevant to decision-making in the clinical use of MTX as a treatment for RA patients harboring the RFC1 gene variant.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-22T09:42:05Z
      DOI: 10.1177/10600280211002053
       
  • Conversion From Continuous Infusion Fentanyl to Continuous Infusion
           Hydromorphone in the Pediatric Intensive Care Unit

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      Authors: Maura Harkin, Jamie L. Miller, Sin Yin Lim, Stephen B. Neely, Christina K. Walsh, Peter N. Johnson
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Opioid rotations from fentanyl to hydromorphone may reduce opioid/sedative exposure in critically ill children.Objective:The primary objective was to determine the conversion percentage from fentanyl to hydromorphone infusions using equianalgesic conversions (0.1 mg fentanyl = 1.5 mg hydromorphone). Secondary objectives included identification of the median time and hydromorphone rate at stabilization (defined as the first 24-hour period no hydromorphone rates changed, 80% of State Behavioral Scale [SBS] scores between 0 and −1, and
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-20T07:28:45Z
      DOI: 10.1177/10600280211003170
       
  • Transthyretin Amyloid Cardiomyopathy—Current and Future Therapies

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      Authors: Jankhna D. Yadav, Harjot Othee, Kelly A. Chan, Damen C. Man, Paul P. Belliveau, Jennifer Towle
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To describe the clinical presentation of transthyretin amyloid cardiomyopathy (ATTR-CM) and discuss current treatments and investigational products and their effect on patient outcomes.Data Sources:A literature search was performed in PubMed (September 2018 to December 2020) using the following keywords: transthyretin amyloidosis, cardiomyopathy, polyneuropathy and transthyretin amyloid cardiomyopathy, monoclonal light-chain, tafamidis, cardiac amyloidosis, ATTR cardiomyopathy, green tea and inhibition of cardiac amyloidosis, AG10, tolcapone, tolcapone and leptomeningeal ATTR, PRX004, NI006, patisiran, inotersen, vutrisiran, AKCEA-TTR-LRx, and NTLA-2001.Study Selection and Data Extraction:Clinical trials were evaluated for evidence supporting pharmacology, safety, efficacy, and measured outcomes.Data Synthesis:Until 2019, there were no approved treatments for ATTR-CM. Treatment consisted of symptom management and organ transplant. Nonpharmacological and pharmacological treatments focused on the symptoms of heart failure (HF) associated with ATTR-CM. However, there are several emerging therapies recently approved or in development to address the underlying pathophysiology. Treatment classes for ATTR-CM include transthyretin stabilizers, human monoclonal antibodies, gene silencers, and CRISPR/Cas9 gene editing.Relevance to Patient Care and Clinical Practice:ATTR-CM is a complex disease in which amyloidosis causes cardiomyopathy. Underdiagnosis is attributed to the clinical presentation being heterogeneous, indistinguishable from HF caused by other etiologies, and the need for invasive testing modalities, including endomyocardial biopsy. Improved diagnostic approaches along with targeted therapies can slow disease progression and enhance patient quality of life.Conclusion:Diagnostic modalities along with biomarker and genetic testing could detect disease earlier and target therapy more accurately. Novel therapies demonstrate potential treatment benefits and can help shape the standard of care for these patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-09T09:38:24Z
      DOI: 10.1177/10600280211000351
       
  • Adjunctive Phenobarbital for Alcohol Withdrawal Syndrome: A Focused
           Literature Review

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      Authors: Julie A. Murphy, Brittany M. Curran, William A. Gibbons, Holly M. Harnica
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review the literature describing the use of adjunctive phenobarbital in the treatment of severe alcohol withdrawal syndrome (AWS).Data Sources:PubMed and EMBASE were searched using the following terms: phenobarbital, adjunct, refractory or treatment resistant, severe or complicated, and alcohol withdrawal delirium or alcohol withdrawal seizures.Study Selection and Data Extraction:The search was limited to randomized controlled trials (RCTs) and cohort studies published in English.Data Synthesis:Seven studies were identified in the emergency department (ED; RCT, n = 1; cohort, n = 2), general medicine ward (cohort, n = 1), and intensive care unit (ICU; cohort, n = 3) settings. For all studies set in the ED and general medicine ward and for 1 ICU study, phenobarbital plus symptom-guided benzodiazepine therapy was compared to symptom-guided benzodiazepine monotherapy. The other 2 ICU studies examined adjunctive phenobarbital before and after implementation of a protocol, meaning patients in both arms could have received phenobarbital. Overall risk of bias across all studies was low to moderate.Relevance to Patient Care and Clinical Practice:The specific role of adjunctive phenobarbital in AWS is not clear because a majority of studies are retrospective cohorts with varying primary outcomes in different patient care settings.Conclusions:In the ED and general medicine ward, phenobarbital demonstrated benzodiazepine-sparing effects. In the ICU, when a protocol guides phenobarbital use, the need for mechanical ventilation may be reduced. Adjunctive phenobarbital was well tolerated. Because of study limitations, it is challenging to provide specific recommendations for adjunctive phenobarbital use in severe AWS.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-08T05:51:48Z
      DOI: 10.1177/1060028021999821
       
  • Creatinine Assessment in Non–Steady-State Conditions: A Critical
           Review

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      Authors: David E. Nix, Brian L. Erstad
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objectives:To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing.Data Sources:A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus.Study Selection and Data Extraction:Articles assessing Clcr under non–steady-state conditions and studies evaluating predictive equations were selected.Data Synthesis:When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcr are appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcr in patients with unstable SCr.Relevance to Patient Care and Clinical Practice:Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcr and most important for estimating glomerular filtration rate. However, standard methods of estimating Clcr for medication dosing are not accurate under non–steady-state conditions.Conclusion:The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-08T05:50:28Z
      DOI: 10.1177/1060028021999644
       
  • The Impact of Body Weight and Renal Function on the Risk of Bleeding With
           Direct Oral Anticoagulants in Atrial Fibrillation

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      Authors: Hannah Whittemore, Andrew K. Posen, Erika L. Hellenbart, Vicki Groo, Eric Wenzler, Jessica J. Tilton
      First page: 1309
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Atrial fibrillation (AF) increases the risk of stroke and direct oral anticoagulants (DOACs) are first-line agents for prevention. Gaps in the literature cause reluctance in prescribing DOACs for patients with renal dysfunction and/or extremes in body weight.Objective:To evaluate the impact body weight and renal function have on major and clinically relevant nonmajor (CRNM) bleeding events and ischemic strokes in AF patients receiving a DOAC.Methods:This retrospective cohort study included adults with nonvalvular atrial fibrillation (NVAF) or atrial flutter (AFL) receiving a DOAC ≥12 months. The primary outcome was a composite of major and CRNM bleeding events. Secondary outcomes included ischemic stroke and risk factors for bleeding events.Results:Of the 233 patients analyzed, 25 patients experienced a bleeding event. Patients who bled weighed 10 kg less (P = 0.043) than those who did not and had a higher HASBLED score (P = 0.003). Multivariate logistic regression identified weight (P = 0.048), serum creatinine (SCr; P = 0.027), and HASBLED score (P = 0.024) as the significant predictors for experiencing a bleed. Three patients experienced a stroke.Conclusion and Relevance:This study demonstrates an association between higher baseline SCr, elevated HASBLED score, and lower weight, with an increased risk of bleeding in patients with NVAF or AFL receiving a DOAC. These findings add to prescribing considerations when initiating DOACs. Closer monitoring is advised for patients with significant renal dysfunction and/or low body weight, even with renal dose adjustments.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-19T09:52:41Z
      DOI: 10.1177/1060028021995201
       
  • Oseltamivir-Associated Bradycardia in Critically Ill Patients

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      Authors: Robert MacLaren, Janelle Francisco, Megan Fetters, Jessica Brady, Crystal Kim, Cameron Welker
      First page: 1318
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Oseltamivir is frequently administered to critically ill patients with presumed influenza. It may modulate Na+, K+, and Ca2+ channels to produce bradycardia.Objective:To evaluate the association between oseltamivir and bradycardia in critically ill patients and assess parameters associated with bradycardia.Methods:This was a retrospective audit of 203 critically ill adults with presumed influenza receiving at least 2 doses of oseltamivir. The primary outcome was the occurrence of bradycardia, defined as a heart rate (HR) ≤59 beats per minute (BPM) while receiving oseltamivir or a decrease of ≥20 BPM compared with the lowest HR before initiating oseltamivir.Results:A total of 88 (43.4%) patients manifested bradycardia, 59 with HR ≤59 BPM, 19 with HR decrease of ≥20 BPM, and 10 with both. The time from first dose to bradycardia was 51.4 ± 43 hours. In all, 48 (54.6%) patients received therapies for bradycardia, including increased inotropic/vasopressor dose, electrolyte replacement, electrocardiogram, discontinuation of other medications, cardiology consult, discontinuation of oseltamivir, and pacer placement. There were no significant differences between groups with bradycardia versus without in terms of demographics, laboratory values, hospital characteristics, or oseltamivir dosing. Multivariate logistic regression showed that bradycardia was associated with baseline HR, age, past medical history of neurological issues, and positive influenza status. Between hours 6 through 126, significant differences existed between groups in actual and lowest HR.Conclusion and Relevance:Oseltamivir was associated with clinically relevant bradycardia in critically ill patients. Clinicians should closely monitor HR in critically ill patients receiving oseltamivir.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-20T10:16:40Z
      DOI: 10.1177/1060028020988919
       
  • Evaluation of Dipeptidyl Peptidase-IV Inhibitor Use in Hospitalized
           Patients With Diabetes

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      Authors: Sarah E. Petite, Maja C. Hill
      First page: 1326
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Glycemic control within goal blood glucose (BG) ranges is essential to minimize hospital complications for patients with type 2 diabetes mellitus (T2DM). Optimal treatment in the non–intensive care unit (ICU) setting includes a basal insulin containing regimen. Dipeptidyl peptidase-IV (DPP-IV) inhibitors have minimal hypoglycemia incidence and may be an appropriate bolus insulin replacement in the inpatient setting.Objective:To determine the effect of basal insulin plus DPP-IV inhibitor compared with basal plus bolus insulin in hospitalized patients with T2DM.Methods:This multicenter cohort study included adult patients with T2DM admitted to the non-ICU setting and prescribed either basal insulin plus DPP-IV inhibitor or basal plus bolus insulin. Propensity-score matching was performed for age, sex, Charlson Comorbidity Index, first BG reading during hospitalization, and hemoglobin A1C (A1C). The primary outcome was the difference in mean daily BG during hospitalization. Secondary outcomes included hospital length of stay (LOS), total daily dose (TDD) of insulin, hypoglycemic events, and mean daily BG in patients with an A1C>8%.Results:A total of 105 patients were included in each group. Mean daily BG during hospitalization was lower in the basal insulin plus DPP-IV inhibitor group (199.3 ± 52.5 vs 213.6 ± 45.8 mg/dL; P = 0.04). There was a significant difference in hospital LOS (5 [interquartile range = 3-8] vs 6 [4-11] days; P = 0.02) and short-acting insulin TDD (11.6 ± 9.1 vs 20.5 ± 21.2 units; P < 0.001). No differences were observed in basal insulin TDD and hypoglycemia. There was no difference in mean daily BG in the subgroup analysis of patients with a A1C>8%.Conclusions and Relevance:A significant difference in mean daily BG and hospital LOS was found with a basal insulin plus DPP-IV inhibitor regimen. Use of a DPP-IV inhibitor to replace bolus insulin in hospitalized patients with T2DM should be considered.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-20T10:17:20Z
      DOI: 10.1177/1060028021996337
       
  • Use of Pediatric Injectable Medicines Guidelines and Associated Medication
           Administration Errors: A Human Reliability Analysis

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      Authors: Matthew D. Jones, Jonathan Clarke, Calandra Feather, Bryony Dean Franklin, Ruchi Sinha, Ian Maconochie, Ara Darzi, Nicholas Appelbaum
      First page: 1333
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:In a recent human reliability analysis (HRA) of simulated pediatric resuscitations, ineffective retrieval of preparation and administration instructions from online injectable medicines guidelines was a key factor contributing to medication administration errors (MAEs).Objective:The aim of the present study was to use a specific HRA to understand where intravenous medicines guidelines are vulnerable to misinterpretation, focusing on deviations from expected practice (discrepancies) that contributed to large-magnitude and/or clinically significant MAEs.Methods:Video recordings from the original study were reanalyzed to identify discrepancies in the steps required to find and extract information from the NHS Injectable Medicines Guide (IMG) website. These data were combined with MAE data from the same original study.Results:In total, 44 discrepancies during use of the IMG were observed across 180 medication administrations. Of these discrepancies, 21 (48%) were associated with an MAE, 16 of which (36% of 44 discrepancies) made a major contribution to that error. There were more discrepancies (31 in total, 70%) during the steps required to access the correct drug webpage than there were in the steps required to read this information (13 in total, 30%). Discrepancies when using injectable medicines guidelines made a major contribution to 6 (27%) of 22 clinically significant and 4 (15%) of 27 large-magnitude MAEs.Conclusion and Relevance:Discrepancies during the use of an online injectable medicines guideline were often associated with subsequent MAEs, including those with potentially significant consequences. This highlights the need to test the usability of guidelines before clinical use.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-01T09:47:16Z
      DOI: 10.1177/1060028021999647
       
  • Impact of Intravenous Methadone Administered Intraoperatively on
           Postoperative Opioid Utilization

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      Authors: Adina Petrosan, Stefanie Zassman, Sara Cohn, Michael Guerra, Karina Soares, James Kennedy, Osama Abdelghany, Elena Gutman
      First page: 1341
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:Studies have shown that intravenous methadone intraoperatively can reduce opioid usage postoperatively.Objective:This study’s purpose was to evaluate the effect of intravenous methadone on postoperative opioid use.Methods:A prospective, single-center observational study was conducted to evaluate patients who received intravenous methadone intraoperatively. A control group was identified by matching procedure, gender, and age in a 1:3 ratio of methadone to control. Exclusion criteria included patients less than 18 years old or on methadone maintenance therapy. The primary outcome was morphine milligram equivalents (MME) administered 24h postoperatively. Secondary outcomes included MME administered 48h and 72h postoperatively, discharge prescription MME, daily mean postoperative pain scores, and length of hospital stay. A subgroup analysis was performed comparing opioid-naïve patients.Results:A total of 240 patients were included in the analysis. At 24h, postoperative MME was increased in the methadone group (142.6 vs 84.5; P = 0.0026). Postoperative MME was also increased in the methadone group at 48h and 72h. Daily pain scores were similar between both groups at all time intervals. Discharge prescription MME was reduced in the methadone group compared with controls, but not statistically significant. A subgroup analysis of opioid-naïve patients showed a significant reduction in MME at 48h (P = 0.0240) and daily pain scores at 24h (P = 0.0366) in the methadone group.Conclusion and Relevance:Intravenous methadone intraoperatively did not show a significant reduction in postoperative opioid use and discharge prescription MMEs when comparing all patients; however, benefit was seen when examining opioid-naïve patients.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-20T10:17:40Z
      DOI: 10.1177/1060028021997390
       
  • Evaluation of Delirium in Critically Ill Patients Prescribed Melatonin or
           Ramelteon

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      Authors: Natasha Romero, Kevin M. Dube, Kenneth E. Lupi, Jeremy R. DeGrado
      First page: 1347
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:An impaired sleep-wake cycle may be one factor that affects the development of delirium in critically ill patients. Several small studies suggest that exogenous melatonin or ramelteon may decrease the incidence and/or duration of delirium.Objective:To compare the effect of prophylactic administration of melatonin, ramelteon, or no melatonin receptor agonist on the development of delirium in the intensive care unit (ICU).Methods:This was a single-center, retrospective, observational cohort study of nondelirious patients in the ICU who received melatonin, ramelteon, or no melatonin receptor agonist. The primary end point was the incidence of delirium. Secondary end points included assessments of daily level of sedation and daily utilization of antipsychotic, sedative, and opioid agents.Results:No difference was observed in the incidence of delirium among the melatonin, ramelteon, and placebo cohorts (18.7% vs 14.3% vs 13.8%; P = 0.77). A difference was observed in the rate of agitation and sedation among the 3 groups, with the greatest observed in the melatonin cohort. Additionally, there was a difference in the use of propofol, dexmedetomidine, and opioids. Overall, there was no difference in clinical outcomes, including duration of mechanical ventilation and ICU or hospital length of stay.Conclusion and Relevance:Therapy with melatonin, ramelteon, and no melatonin receptor agonist resulted in similar rates of delirium in a mixed ICU population. Despite significant differences in agitation, sedation, and medication utilization, there was no differences in the clinical outcomes evaluated.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-15T04:30:54Z
      DOI: 10.1177/10600280211002054
       
  • Resources Assessment for Penicillin Allergy Testing Performed by
           Pharmacists at the Patient’s Bedside

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      Authors: Sophie Gaudreau, Geneviève Bourque, Kevin Côté, Clément Nutu, Marie-France Beauchesne, Audrey-Anne Longpré, Bianca Beloin-Jubinville, Lorraine Legeleux, Martin Blaquière, Philippe Martin, Mélanie Gilbert
      First page: 1355
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Background:False penicillin allergies lead to increased antimicrobial resistance, adverse effects, and health care costs by promoting the use of broad-spectrum antibiotics. The Infectious Diseases Society of America recommends the implementation of allergy testing.Objectives:The primary objective of this research was to estimate the number of pharmacist full-time equivalents (FTEs) required for an intervention aimed at determining penicillin allergy in hospitalized patients. Acceptance of pharmacists’ suggestions on antibiotic therapy are described.Methods:A quasi-experimental study was conducted in a 712-bed university hospital involving hospitalized patients with a suspected penicillin allergy and an infection treatable with penicillin. The time required for the intervention, which included a questionnaire, penicillin allergy testing (skin-prick test, intradermal injection, and oral provocation test), and recommendations on antibiotic therapy were measured to calculate the number of pharmacist FTEs.Results:A total of 55 patients were included. Scarification allergy testing was performed on 37, intradermal allergy test on 33, and oral provocation test on 26 patients. The intervention ruled out penicillin allergy in 26 patients, with no serious adverse effects. The intervention was associated with a median weekly pharmacist FTE of 0.15 (interquartile range = 0.12-0.25). The acceptance of pharmacists’ suggestions was high and led to 9 patients being switched to an antibiotic with a narrower spectrum of activity.Conclusions and Relevance:This study describes penicillin allergy testing and the number of median weekly hospital pharmacist FTEs required, which was approximately 0.15. These data may aid in the implementation of this safe intervention that promotes narrower-spectrum antibiotherapy.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-11T12:52:57Z
      DOI: 10.1177/10600280211002412
       
  • High-Dose Daptomycin and Clinical Applications

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      Authors: Timothy W. Jones, Ah Hyun Jun, Jessica L. Michal, William J. Olney
      First page: 1363
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To evaluate evidence for high-dose daptomycin (doses ≥ 8 mg/kg/d).Data Sources:A PubMed/MEDLINE literature search was performed (January 2000 to December 2020) using the search terms daptomycin, high dose, and dosing. Review article references and society guidelines were reviewed.Study Selection and Data Extraction:Clinical trials, observational studies, retrospective studies, meta-analyses, and systematic reviews reporting on high-dose daptomycin were included.Data Synthesis:Experimentally, daptomycin outperforms other antimicrobials for high inoculum and biofilm-associated infections. Clinically, high-dose daptomycin is supported as salvage and first-line therapy for endocarditis and bacteremia, primarily when caused by methicillin-resistant Staphylococcus aureus (when vancomycin minimum inhibitory concentration is>1 mg/L) and Enterococcus. High-dose daptomycin appears effective for osteomyelitis and central nervous system infections, although comparative studies are lacking. High dosing in renal replacement therapy requires considering clearance modality to achieve exposures like normal renal function. Weight-based dosing in obesity draws concern for elevated exposures, although high doses have not been evaluated kinetically in obesity. Some data show benefits of high doses in overweight populations. Burn patients clear daptomycin more rapidly, and high doses may only achieve drug exposures similar to standard doses (6 mg/kg).Relevance to Patient Care and Clinical Practice:This review analyzes the efficacy and safety of high-dose daptomycin in serious gram-positive infections. Discussion of specific infectious etiologies and patient populations should encourage clinicians to evaluate their daptomycin dosing standards.Conclusions:The efficacy of high-dose daptomycin and limited safety concerns encourage clinicians to consider high-dose daptomycin more liberally in severe gram-positive infections.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-04T09:41:10Z
      DOI: 10.1177/1060028021991943
       
  • Therapeutic Controversies in the Medical Management of Valvular Heart
           Disease

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      Authors: Arden R. Barry, Erica H. Z. Wang
      First page: 1379
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To evaluate the evidence for common therapeutic controversies in the medical management of valvular heart disease (VHD).Data Sources:A literature search of PubMed (inception to December 2020) was performed using the terms angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and aortic stenosis (AS); and adrenergic β-antagonists and aortic valve regurgitation (AR) or mitral stenosis (MS).Study Selection and Data Extraction:Randomized controlled trials (RCTs) and meta-analyses conducted in humans and published in English that reported ≥1 clinical outcome were included.Data Synthesis:Nine articles were included: 3 RCTs and 1 meta-analysis for ACE inhibitors/ARBs in AS, 1 RCT for β-blockers in AR, and 4 RCTs for β-blockers in MS. Evidence suggests that ACE inhibitors/ARBs do not increase the risk of adverse outcomes in patients with AS but may delay valve replacement. β-Blockers do not appear to worsen outcomes in patients with chronic AR and may improve left-ventricular function in patients with a reduced ejection fraction. β-Blockers do not improve and may actually worsen exercise tolerance in patients with MS in sinus rhythm.Relevance to Patient Care and Clinical Practice:ACE inhibitors/ARBs and β-blockers can likely be safely used in patients with AS or AR, respectively, who have a compelling indication. There is insufficient evidence to recommend routine use of β-blockers in patients with MS without atrial fibrillation.Conclusions:Common beliefs about the medical treatment of VHD are not supported by high-quality data. There remains a need for larger-scale RCTs in the medical management of VHD.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-06T12:09:48Z
      DOI: 10.1177/1060028021992329
       
  • Mechanisms and Potential Roles of Glucose-Lowering Agents in COVID-19: A
           Review

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      Authors: Helen D. Berlie, Pramodini B. Kale-Pradhan, Tara Orzechowski, Linda A. Jaber
      First page: 1386
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To explore mechanistic benefits of glucose-lowering agents that extend beyond glycemic control with the potential to mitigate coronavirus disease 2019 (COVID-19) complications.Data Sources:The following PubMed literature search terms were used from July 2020 to January 2, 2021: diabetes, COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), glucose-lowering agents, and pharmacology.Study Selection and Data Extraction:English-language studies reporting on the association between diabetes, COVID-19 adverse outcomes, and the potential roles of glucose-lowering agents were reviewed.Data Synthesis:Selected glucose-lowering agents have benefits beyond glycemic control, with the potential to reduce the risks of severe complications during SARS-CoV-2 infection. Key benefits include anti-inflammatory, anticoagulant, immune modulating, and enzyme/receptor effects.Relevance to Patient Care and Clinical Practice:This review summarizes the current knowledge of glucose-lowering agents and their potential roles in COVID-19 outcomes. Considering beneficial mechanisms on COVID-19 outcomes that extend beyond glycemic control as well as safety profiles, current data suggest that dipeptidyl peptidase-IV (DPP-IV) inhibitors and metformin may have the most promise and warrant further investigation.Conclusions:Certain glucose-lowering agents may offer additional benefits beyond glucose control—namely, by modulating the mechanisms contributing to adverse outcomes related to COVID-19 in patients with diabetes. DPP-IV inhibitors and metformin appear to have the most promise. However, current published literature on diabetes medications and COVID-19 should be interpreted with caution. Most published studies are retrospective and consist of convenience samples, and some lack adequate analytical approaches with confounding biases. Ongoing trials aim to evaluate the effects of glucose-lowering agents in reducing the severity of COVID-19 outcomes.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-04T09:41:59Z
      DOI: 10.1177/1060028021999473
       
  • Cabotegravir-Rilpivirine: The First Complete Long-Acting Injectable
           Regimen for the Treatment of HIV-1 Infection

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      Authors: Spencer H. Durham, Elias B. Chahine
      First page: 1397
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review the efficacy and safety of cabotegravir (CAB) with rilpivirine (RPV) in the treatment of HIV-1 infection.Data Sources:A literature search was performed using PubMed and Google Scholar (2010 to January 2021) with the search terms cabotegravir and rilpivirine. Other resources included abstracts presented at recent conferences and the manufacturer’s website and prescribing information.Study Selection:All English-language articles of studies assessing the efficacy and safety of CAB with RPV were included.Data Synthesis:The combination of CAB, a new integrase strand transfer inhibitor, and RPV, an established nonnucleoside reverse transcriptase inhibitor, is the first long-acting dual therapy approved for the treatment of HIV-1 infection in adults who have achieved viral suppression on a standard antiretroviral therapy (ART). This regimen demonstrated comparable maintenance of viral suppression evaluated up to 160 weeks, with low rates of virological failure. CAB and RPV are available as suspension given intramuscularly in 2 separate injections every 4 weeks. Common adverse effects include injection site reactions, pyrexia, fatigue, and headache. CAB and RPV are also available as tablets given orally for bridging therapy.Relevance to Patient Care and Clinical Practice:This long-acting dual therapy represents an attractive option with a high barrier to resistance for adults who have achieved viral suppression on standard ART and who prefer monthly injections over daily oral therapy.Conclusions:CAB-RPV is the first complete long-acting injectable that provides a convenient way to maintain viral suppression with no negative effects on renal and bone health and few drug interactions.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-17T05:20:47Z
      DOI: 10.1177/1060028021995586
       
  • A Review of Fam-Trastuzumab Deruxtecan-nxki in HER2-Positive Breast Cancer

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      Authors: Xoan Nguyen, Morgan Hooper, Jared Paul Borlagdan, Alison Palumbo
      First page: 1410
      Abstract: Annals of Pharmacotherapy, Ahead of Print.
      Objective:To review the pharmacology, efficacy, and safety of antibody-drug conjugate fam-trastuzumab deruxtecan-nxki in the treatment of advanced, unresectable, or metastatic breast cancer.Data Sources:Relevant information was identified through a MEDLINE/PubMed (January 2015 to December 2020) literature search. The new drug application, prescribing information, clinical practice guideline, and abstracts from scientific meetings were also reviewed.Study Selection and Data Extraction:The literature search was limited to human studies published in the English language. All studies evaluating the pharmacology, efficacy, or safety of fam-trastuzumab deruxtecan-nxki for breast cancer were included.Data Synthesis:Fam-trastuzumab deruxtecan-nxki is composed of an anti–human epidermal growth factor receptor 2 (HER2) antibody and topoisomerase I inhibitor (DXd), which causes DNA damage and apoptotic cell death. Major phase I and phase II clinical trials established the efficacy and safety of fam-trastuzumab deruxtecan-nxki for treatment of HER2-positive advanced, unresectable, or metastatic breast cancers that are refractory or intolerant to standard treatment. In these trials, the response rate was 60.9% (95% CI = 53.4-68.0) Common adverse effects included fatigue, nausea, vomiting, decreased appetite, constipation, diarrhea, alopecia, neutropenia, anemia, and thrombocytopenia. Serious adverse effects included interstitial lung disease or pneumonia, febrile neutropenia, left ventricular dysfunction, and embryo-fetal toxicity.Relevance to Patient Care and Clinical Practice:Fam-trastuzumab deruxtecan-nxki is an option for HER2-positive breast cancer following 2 previous lines of HER2-targeted therapy.Conclusions:Fam-trastuzumab deruxtecan-nxki is an effective treatment for HER2-positive breast cancer in the metastatic setting, but randomized controlled trials are needed.
      Citation: Annals of Pharmacotherapy
      PubDate: 2021-02-25T11:15:29Z
      DOI: 10.1177/1060028021998320
       
  • Caveats in Kidney Function Assessment

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      Authors: Brian L. Erstad, David E. Nix
      First page: 1419
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-09T09:36:10Z
      DOI: 10.1177/10600280211000347
       
  • Successful Alectinib Treatment Administered by Mixing With a Soft Diet in
           a Patient With Non–Small-Cell Lung Cancer With Severe Dysphagia

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      Authors: Silvia Vázquez-Gómez, Jaime Gulín-Dávila, Araceli Iglesias-Santamaría, I. Rodríguez-Losada, Natalia Fernández-Núñez
      First page: 1423
      Abstract: Annals of Pharmacotherapy, Ahead of Print.

      Citation: Annals of Pharmacotherapy
      PubDate: 2021-03-09T09:34:10Z
      DOI: 10.1177/10600280211000703
       
 
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