A Real-World Matched Cohort Study of the Effect of Concomitant Amiodarone or Diltiazem Administration on Apixaban Peak and Trough Concentrations.

BACKGROUND: Apixaban is a substrate for p-glycoprotein and is extensively metabolized by cytochrome P450 (CYP) 3A4. There are minimal published data regarding the effect of amiodarone and diltiazem on apixaban serum concentrations. OBJECTIVE: The aim of this study was to determine the degree of elevation of apixaban concentrations resulting from amiodarone or diltiazem. METHODS: This was a matched cohort study approved by the Institutional Review Board. Patients receiving apixaban 5 mg twice daily with concomitant diltiazem or amiodarone were enrolled. Control groups were enrolled via matching characteristics of sex, age, weight, creatinine clearance, and statin therapy. Exclusions were an inappropriate dosage of apixaban or concomitant dronedarone, verapamil, ranolazine, naproxen, or both amiodarone and diltiazem. Blood samples were collected 3-4 h after and 0.5-2 h before an apixaban dose, corresponding to peak and trough concentrations, respectively. Results were compared using a t test. RESULTS: Thirty patients were enrolled in each of the four groups. The mean peak apixaban concentration was 239 ± 82 ng/mL in the amiodarone group and 208 ± 66 ng/mL in the corresponding control group (p = 0.068). Trough concentrations were 142 ± 71 ng/mL and 117 ± 41 ng/mL, respectively (p = 0.055). The mean peak apixaban concentration was 243 ± 99 ng/mL in the diltiazem group and 213 ± 82 ng/mL in the control group (p = 0.11). Trough concentrations were 130 ± 65 ng/mL and 108 ± 54 ng/mL, respectively (p = 0.09). CONCLUSION: Coadministration of amiodarone and diltiazem resulted in a trend toward increased apixaban concentrations. The extent of elevation suggests that empiric dose changes are not necessary; however, individual patients may benefit from monitoring and dose adjustment.

Assessment of Anti-Xa activity in patients receiving concomitant apixaban with strong p-glycoprotein inhibitors and statins.

WHAT IS KNOWN AND OBJECTIVES: Although the apixaban Food and Drug Administration (FDA) package insert recommends dose reduction in patients administered dual strong inhibitors of p-glycoprotein (P-gp) and cytochrome P-450 (CYP) 3A4, there are limited published data regarding potential drug-drug interactions between apixaban (Eliquis) and common p-glycoprotein (P-gp) and CYP3A4 inhibitors co-administered with statins. The aim of this study was to investigate the degree of elevation relative to apixaban serum peak and trough concentration after the co-administration of amiodarone, diltiazem and statins (atorvastatin, rosuvastatin and simvastatin). METHODS: Patients prescribed apixaban 5mg twice daily for at least one week were identified from the anticoagulation clinic database and contacted for potential enrolment. A total of 117 volunteers were enrolled with eight excluded due to discontinued use, resulting in 109 volunteers (44 females and 65 males delineated into age groups 40-64 and ≥65 years old) completing the observational study. Fifty-five volunteers were administered apixaban without the P-gp inhibitors amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin and simvastatin). Fifty-four volunteers were administered apixaban with either amiodarone or diltiazem, with or without statins (atorvastatin, rosuvastatin or simvastatin). Peak and trough concentrations were assessed for each patient utilizing an apixaban anti-Xa assay. RESULTS: Of the combinations studied, the mean apixaban trough concentration upon co-administration of amiodarone without a statin was elevated compared to apixaban alone (experimental 156.83 +/- 79.59 ng/ml vs. control 104.09 +/- 44.56 ng/ml; p = 0.04). The co-administration of diltiazem and rosuvastatin, and the administration of amiodarone without a statin led to greater than 1.5-fold increase in apixaban concentrations (peak experimental 315.19 +/- 157.53 ng/ml vs control 207.6 +/- 83.38 ng/ml; p = 0.08 and trough experimental 182.03 +/- 95.93 ng/ml vs control 112.32 +/- 37.78 ng/ml; p = 0.17) suggesting the need to assess dose adjustment for patients per the FDA package insert. In addition, the aggregated mean peak (p = 0.0056) and trough (p = 0.0089) elevation of CYP3A4 experimental groups (atorvastatin and simvastatin) co-administered apixaban and diltiazem were statistically significant compared with the aggregated non-CYP3A4 control groups (no statin and rosuvastatin). WHAT IS NEW AND CONCLUSION: Herein, we report novel data regarding peak and trough apixaban concentrations after concomitant administration of P-gp and CYP3A4 inhibitors (amiodarone or diltiazem) co-administered with statins (atorvastatin, rosuvastatin or simvastatin). Providers should consider utilizing the apixaban anti-Xa assay or comparative heparin anti-Xa assay to determine if patients require dose reduction to decrease adverse events in high-risk patients prescribed apixaban and concomitant p-glycoprotein and CYP3A4 inhibitors amiodarone or diltiazem with and without a CYP3A4 or non-3A4 statin.

Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases.

Probiotics are heavily advertised to promote a healthy gastrointestinal tract and boost the immune system. This review article summarizes the history and diversity of probiotics, outlines conventional in vitro assays and in vivo models, assesses the pharmacologic effects of probiotic and pharmaceutical co-administration, and the broad impact of clinical probiotic utilization for gastrointestinal disease indications.

Student response to reports of unprofessional behavior: assessing risk of subsequent professional problems in medical school.

BACKGROUND: An early concern note (ECN) program is used by some medical schools to identify, counsel, and intervene when students exhibit unprofessional behavior. Student maturity, insight, propensity for reflection, and receptiveness to feedback have been suggested as predictors of future behavior. OBJECTIVE: We hypothesized that (a) classifying students with a first ECN based on their response to the report would identify students at risk of repeat ECNs better than the action that prompted it and (b) receipt of multiple ECNs would identify students at risk of adverse academic events. DESIGN: For this study, 459 ECNs were classified based on students' (1) recognition that their behavior was inappropriate and (2) acceptance of responsibility for the behavior. Student academic progress and receipt of subsequent ECNs were tracked. RESULTS: Students who recognized their behavior was inappropriate and accepted responsibility after an initial ECN received subsequent ECNs at lower rates (14-19%) than students who disagreed with the significance of their behavior or were resistant to accepting responsibility (36-59%). Students with limited insight and adaptability appeared to be at highest risk. Seventy-one percent of students with three or more ECNs encountered adverse academic events during enrollment. CONCLUSION: Student reactions to reports of unprofessional behavior may be useful as a tool to help assess risk of recurrent lapses. Students with diminished capacity to recognize behaviors as unprofessional or accept responsibility for them appear to be at highest risk for additional adverse academic and professionalism events while in medical school.

The Cancer Genomics Hub (CGHub): overcoming cancer through the power of torrential data.

The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. The CGHub currently contains >1.4 PB of data, has grown at an average rate of 50 TB a month and serves >100 TB per week. The architecture of CGHub is designed to support bulk searching and downloading through a Web-accessible application programming interface, enforce patient genome confidentiality in data storage and transmission and optimize for efficiency in access and transfer. In this article, we describe the design of these three components, present performance results for our transfer protocol, GeneTorrent, and finally report on the growth of the system in terms of data stored and transferred, including estimated limits on the current architecture. Our experienced-based estimates suggest that centralizing storage and computational resources is more efficient than wide distribution across many satellite labs. Database URL: https://cghub.ucsc.edu.

Effects of comprehensive educational reforms on academic success in a diverse student body.

CONTEXT: Calls for medical curriculum reform and increased student diversity in the USA have seen mixed success: performance outcomes following curriculum revisions have been inconsistent and national matriculation of under-represented minority (URM) students has not met aspirations. Published innovations in curricula, academic support and pipeline programmes usually describe isolated interventions that fail to affect curriculum-level outcomes. METHODS: United States Medical Licensing Examination (USMLE) Step 1 performance and graduation rates were analysed for three classes of medical students before (matriculated 1995-1997, n=517) and after (matriculated 2003-2005, n=597) implementing broad-based reforms in our education system. The changes in pipeline recruitment and preparation programmes, instructional methods, assessment systems, academic support and board preparation were based on sound educational principles and best practices. RESULTS: Post-reform classes were diverse with respect to ethnicity (25.8% URM students), gender (51.8% female), and Medical College Admissions Test (MCAT) score (range 20-40; 24.1% scored ≤ 25). Mean±standard deviation MCAT scores were minimally changed (from 27.2±4.7 to 27.8±3.6). The Step 1 failure rate decreased by 69.3% and mean score increased by 14.0 points (effect size: d=0.67) overall. Improvements were greater among women (failure rate decreased by 78.9%, mean score increased by 15.6 points; d=0.76) and URM students (failure rate decreased by 76.5%, mean score increased by 14.6 points; d=0.74), especially African-American students (failure rate decreased by 93.6%, mean score increased by 20.8 points; d=1.12). Step 1 scores increased across the entire MCAT range. Four- and 5-year graduation rates increased by 7.1% and 5.8%, respectively. CONCLUSIONS: The effect sizes in these performance improvements surpassed those previously reported for isolated interventions in curriculum and student support. This success is likely to have resulted from the broad-based, mutually reinforcing nature of reforms in multiple components of the education system. The results suggest that a narrow reductionist view of educational programme reform is less likely to result in improved educational outcomes than a system perspective that addresses the coordinated functioning of multiple aspects of the academic enterprise.

Do students do what they write and write what they do? The match between the patient encounter and patient note.

BACKGROUND: Patient notes are used for a variety of purposes in health care. Medical students are taught the structure of patient notes early in training. Review of patient notes are then used to assess synthesis and integration of patient information. It is critical that the information in the note accurately and completely represents the student-patient encounter. METHOD: The authors reviewed videotapes of students in three standardized-patient based scenarios and compared what occurred during the physical examination with the subsequent documentation in the patient note. RESULTS: In all, 207 encounter-note pairs were reviewed. Only 8 (4%) of the notes completely and accurately represented what occurred during the encounter. Problems with underdocumentation, overdocumentation, and inaccurate documentation of physical findings were seen for all three patient scenarios. CONCLUSIONS: These findings highlight the need to teach and assess both data gathering skills and written documentation of findings in medical training.

Medical student professionalism: are we measuring the right behaviors? A comparison of professional lapses by students and physicians.

BACKGROUND: Examining the relationship between unprofessional behaviors observed in medical students and those manifested by physicians is important in determining whether medical school faculty are observing and reporting behaviors relevant to medical practice. METHOD: This study compares the relationship between unprofessional behaviors identified in students at our medical school through Early Concern Notes, and behaviors for which physicians were sanctioned by our state medical board. RESULTS: The majority of reports in both groups were related to lapses in professional responsibility and integrity, and the specific behaviors identified in the groups were similar. A smaller number of reports in both groups were related to pursuit of excellence or personal interactions. CONCLUSION: There are common features to the professional shortcomings seen in students at our medical school and practicing physicians in our state. These similarities add credibility to our faculty's observations, and reinforce the relevance of monitoring such behaviors in future physicians.

The Use of Station Time Allotments by Fourth Year Medical Students in a Standardized Patient-Based Clinical Skills Examination.

INTRODUCTION: We performed this study to assess medical student use of station time allotments in a standardized patient-based clinical skills assessment. METHODS: Videotapes of student-SP encounters were reviewed. Total encounter time, and time spend in the physical examination, were recorded in seconds. The mean time use for each station was calculated. Cases were categorized by patient age, case content and acuity. Times were compared across cases. RESULTS: On average, students spent most time in encounters requiring complex interviewing strategies or physical examination maneuvers. Students also spent more time on cases that involved content familiar to them from multiple clerkship disciplines. DISCUSSION: Many factors are believed to influence the use of station time allotments in SP-based clinical skills assessment. Our findings have provided information helpful for case refinement, and may assist others when planning multi-station examinations.

Student Perceptions of the Professional Behavior of Faculty Physicians.

This study was conducted to obtain a baseline understanding of the professional behavior of clinical faculty physicians from the medical students' perspective. Students completed a professionalism evaluation of supervising faculty at the end of each required third-year clerkship over a one year period. Results were analyzed by specific behaviors and across clerkships. Differences were noted in the frequency of the types of problems seen, and varied by clerkship discipline. The most common transgressions of professional behavior reported were the use of derogatory language towards other services or patients and the disrespectful treatment of others. Our study served to provide objective feedback to the faculty about student perceptions of faculty as role models for professionalism while on clinical rotations.