Clinical Utility of Pharmacogenomic Testing to Support Prescriptive Decision Making Among Anesthesia Providers: A Mixed-Method Study

Anesthesia care is delivered world wide on a daily basis. Provision of anesthesia cares for surgical, obstetrical, or pain management procedures mandate a thorough understanding of physiology, pathophysiology, and pharmacology. Nearly 4 million anesthetics are delivered in the United States each year and the impact of genetics on anesthesia care is becoming greater. Anesthesia providers make prescriptive decisions based on an individual patient\u27s disease processes, proposed surgical or therapeutic procedure, and a thorough clinical history. The age of personalized medicine is upon us and the ability to use genetic testing to help predict how a patient will respond to various medications is here. By using genetically coded single nucleotide polymorphism programming of the metabolic pathways in the liver, drugs responsiveness can be more precisely predicted and explained. This dissertation focuses on the clinical utility of genetic testing to predict drug responsiveness (pharmacogenomics) among anesthesia providers with a focus on treating acute pain. Specifically, the following research question is addressed: What is the clinical utility of pharmacogenomic testing to support prescriptive decision making among anesthesia providers. To answer this research question, a mixed-method sequential qualitative quantitative study was carried out. The conclusions of this research are (a) anesthesia providers lack knowledge concerning pharmacogenomic testing, (b) anesthesia providers are concerned about potential ethical and economic issues surrounding genetic testing, and (c) anesthesia providers perceive a potential benefit to using pharmacogenomic testing as it relates to making prescriptive decisions. Further work is necessary to more carefully refine the instrument used to measure clinical utility as well as future intervention work aimed at increasing anesthesia provider knowledge about pharmacogenomic testing

Evaluation of industry payments and financial conflict of interest disclosures among task force authors of Endocrine Society clinical practice guidelines

Introduction: Clinical practice guidelines are considered the gold standard for disease management and treatment. Industry payments to guideline authors may influence their clinical recommendations, potentially resulting in medical and/or financial consequences to patients.Research Question: Determine the extent Endocrine Society guideline authors receive industry payments and report financial conflicts of interest in adherence to the Physician Payments Sunshine Provision of the Affordable Care Act.Study Design: Cross-sectional analysis of all clinical practice guidelines published by the Endocrine Society since the Sunshine Provision mandate.Methods: We searched the Endocrine Society's website for clinical guidelines published between January 2014 and December 2017. Identified guideline authors were independently searched by two investigators on the Open Payments Database. Received payments were extracted and statistically analyzed (excluding food/beverage payments). Payments were cross-referenced with corresponding author disclosure statements.Results: Of the 57 evaluable guideline authors, 34 authors (59.6%) received at least one industry payment. Of these authors, thirty-three (57.89%) received ≥ $1,000, twenty-six (45.61$10,000, twenty-two (38.60%) ≥ $50,000, and twenty-one (36.84$100,000. Sixteen authors (28.07%) received ≥ $250,000 in industry payments. Median total payments were$4,060 (interquartile range [IQR] $0-263,264.23). Twenty-seven (47.37$28,523.93 (IQR $5,714-94,418.02), with a payment total of$2,870,485.27.Conclusion: Industry payments among Endocrine Society clinical practice guideline authors were widespread, with several exceeding $250,000. Nearly half of author disclosure statements were inaccurate. The Endocrine Society's disclosure policy should be more strictly enforced for future guideline authors

Introducing W.A.T.E.R.S.: a Workflow for the Alignment, Taxonomy, and Ecology of Ribosomal Sequences

<p>Abstract</p> <p>Background</p> <p>For more than two decades microbiologists have used a highly conserved microbial gene as a phylogenetic marker for bacteria and archaea. The small-subunit ribosomal RNA gene, also known as 16 S rRNA, is encoded by ribosomal DNA, 16 S rDNA, and has provided a powerful comparative tool to microbial ecologists. Over time, the microbial ecology field has matured from small-scale studies in a select number of environments to massive collections of sequence data that are paired with dozens of corresponding collection variables. As the complexity of data and tool sets have grown, the need for flexible automation and maintenance of the core processes of 16 S rDNA sequence analysis has increased correspondingly.</p> <p>Results</p> <p>We present WATERS, an integrated approach for 16 S rDNA analysis that bundles a suite of publicly available 16 S rDNA analysis software tools into a single software package. The "toolkit" includes sequence alignment, chimera removal, OTU determination, taxonomy assignment, phylogentic tree construction as well as a host of ecological analysis and visualization tools. WATERS employs a flexible, collection-oriented 'workflow' approach using the open-source Kepler system as a platform.</p> <p>Conclusions</p> <p>By packaging available software tools into a single automated workflow, WATERS simplifies 16 S rDNA analyses, especially for those without specialized bioinformatics, programming expertise. In addition, WATERS, like some of the newer comprehensive rRNA analysis tools, allows researchers to minimize the time dedicated to carrying out tedious informatics steps and to focus their attention instead on the biological interpretation of the results. One advantage of WATERS over other comprehensive tools is that the use of the Kepler workflow system facilitates result interpretation and reproducibility via a data provenance sub-system. Furthermore, new "actors" can be added to the workflow as desired and we see WATERS as an initial seed for a sizeable and growing repository of interoperable, easy-to-combine tools for asking increasingly complex microbial ecology questions.</p

Miniature Exoplanet Radial Velocity Array I: design, commissioning, and early photometric results

The Miniature Exoplanet Radial Velocity Array (MINERVA) is a U.S.-based observational facility dedicated to the discovery and characterization of exoplanets around a nearby sample of bright stars. MINERVA employs a robotic array of four 0.7-m telescopes outfitted for both high-resolution spectroscopy and photometry, and is designed for completely autonomous operation. The primary science program is a dedicated radial velocity survey and the secondary science objective is to obtain high-precision transit light curves. The modular design of the facility and the flexibility of our hardware allows for both science programs to be pursued simultaneously, while the robotic control software provides a robust and efficient means to carry out nightly observations. We describe the design of MINERVA, including major hardware components, software, and science goals. The telescopes and photometry cameras are characterized at our test facility on the Caltech campus in Pasadena, California, and their on-sky performance is validated. The design and simulated performance of the spectrograph is briefly discussed as we await its completion. New observations from our test facility demonstrate sub-mmag photometric precision of one of our radial velocity survey targets, and we present new transit observations and fits of WASP-52b—a known hot-Jupiter with an inflated radius and misaligned orbit. The process of relocating the MINERVA hardware to its final destination at the Fred Lawrence Whipple Observatory in southern Arizona has begun, and science operations are expected to commence in 2015

Robo-AO M-dwarf Multiplicity Survey: Catalog

We analyze observations from Robo-AO's field M dwarf survey taken on the 2.1 m Kitt Peak telescope and perform a multiplicity comparison with Gaia DR2. Through its laser-guided, automated system, the Robo-AO instrument has yielded the largest adaptive optics M dwarf multiplicity survey to date. After developing an interface to visually identify and locate stellar companions, we selected 11 low-significance Robo-AO detections for follow-up on the Keck II telescope using NIRC2. In the Robo-AO survey we find 553 candidate companions within 4'' around 534 stars out of 5566 unique targets, most of which are new discoveries. Using a position cross-match with DR2 on all targets, we assess the binary recoverability of Gaia DR2 and compare the properties of multiples resolved by both Robo-AO and Gaia. The catalog of nearby M dwarf systems and their basic properties presented here can assist other surveys which observe these stars, such as the NASA TESS mission

Magnetic Inflation and Stellar Mass. I. Revised Parameters for the Component Stars of the Kepler Low-mass Eclipsing Binary T-Cyg1-12664

Several low-mass eclipsing binary stars show larger than expected radii for their measured mass, metallicity, and age. One proposed mechanism for this radius inflation involves inhibited internal convection and starspots caused by strong magnetic fields. One particular eclipsing binary, T-Cyg1-12664, has proven confounding to this scenario. Çakırlı et al. measured a radius for the secondary component that is twice as large as model predictions for stars with the same mass and age, but a primary mass that is consistent with predictions. Iglesias-Marzoa et al. independently measured the radii and masses of the component stars and found that the radius of the secondary is not in fact inflated with respect to models, but that the primary is, which is consistent with the inhibited convection scenario. However, in their mass determinations, Iglesias-Marzoa et al. lacked independent radial velocity measurements for the secondary component due to the star's faintness at optical wavelengths. The secondary component is especially interesting, as its purported mass is near the transition from partially convective to a fully convective interior. In this article, we independently determined the masses and radii of the component stars of T-Cyg1-12664 using archival Kepler data and radial velocity measurements of both component stars obtained with IGRINS on the Discovery Channel Telescope and NIRSPEC and HIRES on the Keck Telescopes. We show that neither of the component stars is inflated with respect to models. Our results are broadly consistent with modern stellar evolutionary models for main-sequence M dwarf stars and do not require inhibited convection by magnetic fields to account for the stellar radii

Statistical significance and sports medicine trials

Objectives: Lowering the threshold for statistical significance in medical research from a P value of .05 to .005 was recently proposed to reduce misinterpretation of study results. What effect this proposal would have on orthopaedic sports medicine literature is currently unclear.Research Question/Hypothesis: We seek to determine how the newly proposed threshold could affect the interpretation of previously published sports medicine RCTs.Methods: We searched PubMed from January 01, 2016 to December 31, 2017 for RCTs published in the American Journal of Sports Medicine, Arthroscopy, and Knee Surgery, Sports Traumatology, Arthroscopy. We extracted P value data for primary endpoints, since RCTs are most often powered for these endpoints. We used Google Forms for data extraction and STATA 13.1 for the data analysis.Results: Of the 159 studies, only 13 (8%) of the studies have endpoints in which all P values are below the new threshold of .005. 40 (25%) of the studies have endpoints in which some would meet the new P value threshold of .005, and some would not meet this new threshold. 106 (67%) of the studies have no endpoints in which the P value(s) was less than .005. Overall, 38% (59/157) of the previously statistically significant primary endpoints were less than .005, while 62% (98/157) would be reclassified as suggestive.Conclusions: Of statistically significant endpoints in our sample, only 17% (59/350) would maintain their statistical significance with a P value threshold of less than .005, and only 8% of studies would maintain their overall significance with all P values falling below the new threshold