To report the design and implementation of the Right Drug, Right Dose, Right Time-Using Genomic Data to Individualize Treatment protocol that was developed to test the concept that prescribers can ...deliver genome-guided therapy at the point of care by using preemptive pharmacogenomics (PGx) data and clinical decision support (CDS) integrated into the electronic medical record (EMR).
We used a multivariate prediction model to identify patients with a high risk of initiating statin therapy within 3 years. The model was used to target a study cohort most likely to benefit from preemptive PGx testing among the Mayo Clinic Biobank participants, with a recruitment goal of 1000 patients. We used a Cox proportional hazards model with variables selected through the Lasso shrinkage method. An operational CDS model was adapted to implement PGx rules within the EMR.
The prediction model included age, sex, race, and 6 chronic diseases categorized by the Clinical Classifications Software for International Classification of Diseases, Ninth Revision codes (dyslipidemia, diabetes, peripheral atherosclerosis, disease of the blood-forming organs, coronary atherosclerosis and other heart diseases, and hypertension). Of the 2000 Biobank participants invited, 1013 (51%) provided blood samples, 256 (13%) declined participation, 555 (28%) did not respond, and 176 (9%) consented but did not provide a blood sample within the recruitment window (October 4, 2012, through March 20, 2013). Preemptive PGx testing included CYP2D6 genotyping and targeted sequencing of 84 PGx genes. Synchronous real-time CDS was integrated into the EMR and flagged potential patient-specific drug-gene interactions and provided therapeutic guidance.
This translational project provides an opportunity to begin to evaluate the impact of preemptive sequencing and EMR-driven genome-guided therapy. These interventions will improve understanding and implementation of genomic data in clinical practice.
Background Preoperative physical fitness is predictive of postoperative outcome. Patients with lesser aerobic capacity are at greater risk of postoperative complications, longer hospital stays, and ...mortality. Prehabilitation may improve physical fitness, but it is unknown whether enhanced fitness translates to an improvement in postoperative outcome. Methods This systematic review and meta-analysis aimed to assess the ability of prehabilitation to influence postoperative outcome after intra-abdominal operations. Randomized controlled trials with at least 1 group undergoing a preoperative exercise intervention/prehabilitation were included. The following databases were searched: AMED, CINAHL, EMBASE, PubMed/Medline, and The Cochrane Library. Data extracted from 9 full-articles included author(s), population demographics, type of operation, postoperative measures of outcome, and type of treatment of the prehabilitation and control groups. Methodologic quality was assessed using GRADEpro, and the Cochrane risk of bias tool was used to measure study bias. Results Prehabilitation consisting of inspiratory muscle training, aerobic exercise, and/or resistance training can decrease all types of postoperative complications after intra-abdominal operations (odds ratio: 0.59, 95% confidence interval: 0.38–0.91, P = .03). It is unclear from our meta-analysis whether prehabilitation can decrease postoperative length of stay, because the number of studies that examined length of stay was small ( n = 4). No postoperative mortality was reported in any study, and conclusions could not be drawn on the ability of exercise to influence operative mortality. The methodologic quality of studies was, however, “very low.” Conclusion Prehabilitation appears to be beneficial in decreasing the incidence of postoperative complications; however, more high-quality studies are needed to validate its use in the preoperative setting.
Abstract Study objective To assess the ability of field tests of exercise tolerance, such as the 6-minute walk test (6MWT) and incremental shuttle walk test (ISWT), to predict postoperative outcome ...following intra-abdominal surgery. Design A systematic review. Setting A hospital-affiliated university. Measurements The following databases were searched: AMED, CINAHL, EMBASE, PEDro, PubMed/MEDLINE, and The Cochrane Library. Six full-text articles were included. Data extraction included author, population demographics, surgery type, postoperative outcome measure, and field test results. The risk of bias was performed using the Quality in Prognosis Studies tool. Results Surgical procedures reviewed were colorectal (n = 3), upper gastrointestinal (n = 1), and intra-abdominal surgery (n = 2). Field tests of exercise tolerance showed little ability to predict postoperative mortality; however, the overall rate of mortality was low. Patients achieving lower distances on the ISWT tended to have longer hospital stays and an increased risk of overall complications. The 6MWT does not appear able to predict postoperative cardiac or pulmonary complications; however, it may be suitable to predict general complications. Conclusions Field tests may be able to predict postoperative outcome; however, further validation is needed. The ISWT appears to be the superior field test. The 6MWT and stair climb test require further validation to assess their predictive ability.
Abstract Background Limited information is available regarding primary care clinicians’ response to pharmacogenomic Clinical Decision Support (PGx-CDS) alerts integrated in the electronic health ...record. Methods In February 2015, 159 clinicians in the Mayo Clinic primary care practice were sent e-mail surveys to understand their perspectives on the implementation and use of pharmacogenomic testing in their clinical practice. Surveys assessed how the clinicians felt about pharmacogenomics and whether they thought electronic PGx-CDS alerts were useful. Information was abstracted on the number of CDS alerts the clinicians received between October, 2013 and the date their survey was returned. CDS alerts were grouped into two categories: alert recommended caution using the prescription or the alert recommended an alternate prescription. Finally, data were abstracted regarding whether the clinician changed their prescription in response to the alert recommendation. Results The survey response rate was 57% (n=90). Overall, 52% of the clinicians did not expect to use or did not know whether they would use pharmacogenomic information in their future prescribing practices. Additionally, 53% of the clinicians felt that the alerts were confusing, irritating, frustrating, or that it was difficult to find additional information. Finally, only 30% of the clinicians that received a CDS alert changed their prescription to an alternative medication. Conclusions Our results suggest a lack of clinician comfort with integration of pharmacogenomic data into primary care. Further efforts to refine PGx-CDS alerts to make them as useful and user-friendly as possible are needed to improve clinician satisfaction with these new tools.
Design, Synthesis, and Actions of a Novel Chimeric Natriuretic Peptide: CD-NP Ondrej Lisy, Brenda K. Huntley, Daniel J. McCormick, Paul A. Kurlansky, John C. Burnett, Jr C-type natriuretic peptide ...(CNP) has beneficial vascular and antiproliferative properties. While lacking renal actions, CNP is less hypotensive than atrial natriuretic peptide and B-type natriuretic peptide (BNP) but unloads the heart due to venodilation. Dendroaspis natriuretic peptide (DNP) is a potent natriuretic and diuretic peptide but is hypotensive and functions via a separate receptor than CNP. We engineered a chimeric peptide CD-NP that fuses the 22-amino acid (AA) peptide CNP with the 15-AA C-terminus of DNP. Our studies demonstrate that CD-NP is natriuretic and diuretic, glomerular filtration rate enhancing, cardiac unloading, renin inhibiting, and less hypotensive when compared to BNP. CD-NP inhibits cardiac fibroblast proliferation.
Abstract Schwannoma is a proliferation of neoplastic Schwann cells. Whereas schwannomas of the head and neck region are common, intraocular tissues are rarely affected. Uveal schwannoma has been ...aptly called a “pseudomelanoma”, reflecting the difficulty in its clinical distinction from uveal malignant melanoma. Most of our current knowledge on intraocular schwannoma is limited to case reports, short case series, and non-comprehensive literature reviews. Three isolated reports of uveal schwannoma with extrascleral extension exist in literature, but the prognostic significance of this growth pattern is unknown. We present a patient with choroidal schwannoma with extrascleral extension and review 46 previously reported cases of uveal schwannomas to delineate clinical and pathologic characteristics of these intraocular tumors with a specific emphasis on schwannoma with extraocular extension.
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