Cumulative Sum Chart as Complement to Objective Assessment of Graduating Surgical Resident Competency: An Exploratory Study.

BACKGROUND: Rater-based assessment and objective assessment play an important role in evaluating residents' clinical competencies. We hypothesize that a cumulative sum (CUSUM) chart of operative time is a complement to the assessment of chief general surgery residents' competencies with ACGME Milestones, aiding residency programs' determination of graduating residents' practice readiness. STUDY DESIGN: We extracted ACGME Milestone evaluations of performance of operations and procedures (POP) and 3 objective metrics (operative time, case type, and case complexity) from 3 procedures (cholecystectomy, colectomy, and inguinal hernia) performed by 3 cohorts of residents (N = 15) during their PGY4-5. CUSUM charts were computed for each resident on each procedure type. A learning plateau was defined as at least 4 cases consistently locating around the centerline (target performance) at the end of a CUSUM chart with minimal deviations (range 0 to 1). RESULTS: All residents reached the ACGME graduation targets for the overall POP by the end of chief year. A total of 2,446 cases were included (cholecystectomy N = 1234, colectomy N = 507, and inguinal hernia N = 705), and 3 CUSUM chart patterns emerged: skewed distribution, bimodal distribution, and peaks and valleys distribution. Analysis of CUSUM charts revealed surgery residents' development processes in the operating room towards a learning plateau vary, and only 46.7% residents reach a learning plateau in all 3 procedures upon graduation. CONCLUSIONS: CUSUM charts of operative time complement the ACGME Milestones evaluations. The use of both may enable residency programs to holistically determine graduating residents' practice readiness and provide recommendations for their upcoming career/practice transition.

Could Aspirin and Diets High in Fiber Act Synergistically to Reduce the Risk of Colon Cancer in Humans?

Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from colon cancer mortality. The lower aspirin doses causing only minimal gastrointestinal disturbance, ideal for long-term use, can achieve only partial and transitory inhibition of COX2. Aspirin's principal metabolite, salicylic acid, is also found in fruits and vegetables that inhibit COX2. Other phytochemicals such as curcumin, resveratrol, and anthocyanins also inhibit COX2. Such dietary components are good candidates for combination with aspirin because they have little or no toxicity. However, obstacles to using phytochemicals for chemoprevention, including bioavailability and translational potential, must be resolved. The bell/U-shaped dose-response curves seen with vitamin D and resveratrol might apply to other phytochemicals, shedding doubt on 'more is better'. Solutions include: (1) using special delivery systems (e.g., nanoparticles) to retain phytochemicals; (2) developing robust pharmacodynamic biomarkers to determine efficacy in humans; and (3) selecting pharmacokinetic doses relevant to humans when performing preclinical experiments. The combination of aspirin and phytochemicals is an attractive low-cost and low-toxicity approach to colon cancer prevention that warrants testing, particularly in high-risk individuals.

Reflecting on a decade of metabolite screening and monitoring.

The last 10 years have witnessed robust debate within the bioanalytical community and regulatory authorities on the topic of metabolite monitoring and safety assessment. Of particular interest to regulated bioanalytical laboratories was the acceptance by the US FDA and other major regulatory bodies of a tiered approach to bioanalytical assay validation. The tiered approach defines a sliding scale of regulatory rigor for the evaluation of significant human metabolites that encompasses a range of assessments from semi-quantitative assays to fully validated assays, all of which can be used in support of regulatory submissions. This article describes the utilization of a tiered approach at Bristol-Myers Squibb and the decision trees guiding the selection of the appropriate level of assay qualification. Case studies illustrate how decisions are made, how different scientific situations influence the assay choice, and what criteria may be set to continue or discontinue metabolite monitoring in later drug development.

Effective screening approach to select esterase inhibitors used for stabilizing ester-containing prodrugs analyzed by LC-MS/MS.

BACKGROUND: Analysis of prodrugs, with their short half-lives, especially ester-containing ones, poses a unique challenge in developing and validating bioanalytical assays for nonclinical and clinical studies. A screening approach is needed to expeditiously select esterase inhibitors for stabilizing them during sample collection and processing. RESULTS: The screening process consisted of three steps. Initially, nine different esterase inhibitors were screened at three different plasma concentrations against an ester prodrug. Four inhibitors were chosen for the next step, in which plasma pH and processing temperature were optimized. Finally, whole-blood stability of the prodrug was evaluated. Three inhibitors with optimized plasma pH and processing temperature were selected for further bioanalytical assay development. CONCLUSION: An effective approach was successfully developed to promptly select suitable esterase inhibitors for stabilizing ester-containing prodrugs.