Recommendations for pharmacogenetic testing in clinical practice guidelines in the US.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: Pharmacogenetic testing can identify patients who may benefit from personalized drug treatment. However, clinical uptake of pharmacogenetic testing has been limited. Clinical practice guidelines recommend biomarker tests that the guideline authors deem to have demonstrated clinical utility, meaning that testing improves treatment outcomes. The objective of this narrative review is to describe the current status of pharmacogenetic testing recommendations within clinical practice guidelines in the US. SUMMARY: Guidelines were reviewed for pharmacogenetic testing recommendations for 21 gene-drug pairs that have well-established drug response associations and all of which are categorized as clinically actionable by the Clinical Pharmacogenetics Implementation Consortium. The degree of consistency within and between organizations in pharmacogenetic testing recommendations was assessed. Relatively few clinical practice guidelines that provide a pharmacogenetic testing recommendation were identified. Testing recommendations for HLA-B*57:01 before initiation of abacavir and G6PD before initiation of rasburicase, both of which are included in drug labeling, were mostly consistent across guidelines. Gene-drug pairs with at least one clinical practice guideline recommending testing or stating that testing could be considered included CYP2C19-clopidogrel, CYP2D6-codeine, CYP2D6-tramadol, CYP2B6-efavirenz, TPMT-thiopurines, and NUDT15-thiopurines. Testing recommendations for the same gene-drug pair were often inconsistent between organizations and sometimes inconsistent between different guidelines from the same organization. CONCLUSION: A standardized approach to evaluating the evidence of clinical utility for pharmacogenetic testing may increase the inclusion and consistency of pharmacogenetic testing recommendations in clinical practice guidelines, which could benefit patients and society by increasing clinical use of pharmacogenetic testing.

Use of an automated mobile application to assess effects of nicotine withdrawal on verbal fluency: A pilot study.

Mild-to-moderate impairment in frontally mediated functions such as sustained attention, working memory, and inhibition have been found to occur during tobacco withdrawal and may present a barrier to successful cessation. These findings have led to studies evaluating cessation treatments that target nicotine withdrawal related cognitive impairment. The instruments currently used to assess cognitive function provide detailed and specific information but have limitations including being time consuming, cumbersome, anxiety provoking, and having poor ecological validity. The authors examined the feasibility of using a mobile computer application to test verbal fluency (VF) as a quick, easy-to-administer, and more ecologically valid method of measuring the effects of short-term smoking abstinence on frontally mediated cognitive functions. Thirty participants completed 2 assessments-1 during ad lib smoking and 1 after overnight abstinence. At each assessment, semantic and phonemic VF tests were administered using a mobile application and nicotine craving and withdrawal symptom severity was assessed. In repeated assessments, performance on both semantic and phonemic VF tests is expected to improve due to practice effects; however, significant improvements were observed only in semantic (p = .012) but not phonemic (p = .154) VF. In addition, the change between assessments in phonemic (but not semantic) score was significantly associated with withdrawal (p = .006) and craving (p = .037) severity measured postabstinence. This study demonstrates that nicotine withdrawal has differential effects on semantic versus phonemic VF suggesting impairments of working memory, attention, and inhibition. These effects were measured using methods easily used in large groups of participants, potentially with remote test administration and automated scoring. (PsycINFO Database Record

A Comparison of Circumstances at the End of Life in a Hospital Setting for Children With Palliative Care Involvement Versus Those Without.

CONTEXT: Specialized pediatric palliative care (PPC) services have become more common in urban pediatric hospital settings, although little is known about palliative care specialist involvement. OBJECTIVES: The objective of this study was to compare circumstances before death in children who spent their last days of life in an inpatient pediatric hospital setting, with or without PPC provider involvement during their inpatient stay. METHODS: Retrospective chart review of medical records of children for the last inpatient stay that resulted in death at a children's hospital setting between January 2012 through June 2013. The setting was a free-standing, 385-bed tertiary care children's hospital. RESULTS: Charts were reviewed for 114 children between 0 and 18 years of age, who were hospitalized for at least 24 hours before their death. Half of the children who died as inpatients were infants (median age five weeks). Children who received an inpatient PPC consult (25% of the sample) experienced 1) a higher rate of pain assessments, 2) better documentation around specific actions to manage pain, 3) greater odds of receiving integrative medicine services, 4) fewer diagnostic/monitoring procedures (e.g., blood gases, blood draws, placements of intravenous lines) in the last 48 hours of life, and 5) nearly eight times greater odds of having a do-not-resuscitate order in place at the time of death. CONCLUSION: The integration of a PPC team was associated with fewer diagnostic/monitoring procedures and improved pain management documentation in this study of 114 children who died as inpatients.