Reducing Reliance on Test Scores Reduces Racial Bias in Neurology Residency Recruitment.

PURPOSE: We sought to correct a low interview rate for racial groups underrepresented in medicine (URM) by analyzing our interview selection process, identifying sources of unintended bias, and developing a new process that would provide a more racially diverse interview pool. METHODS: We analyzed our review process to determine at which point we were eliminating URM candidates at a higher rate than those who are not from an underrepresented group. A point system was created incorporating clinical grades, extracurricular activities, research, letters of recommendation, board exam scores, and life experiences. We compared the rate at which interviews were offered to URM candidates and compared those rates to historical data. We then analyzed the new process by comparing groups who were offered interviews to those who were not. RESULTS: In 2016, 56% of URM applicants were screened out by a mandatory minimum United States Medical Licensing Examination (USMLE) test score, whereas only 39% of all other groups were disqualified by test scores. This led to 20% of the URM applicants receiving interview offers. By comparison, 30.6% of other groups were offered interviews. After removing the required minimum test score for application review and modifying the screening process to a more holistic one the following application cycle, 24.5% of URMs were offered interviews in 2017 compared to 28.1% of others. CONCLUSIONS: A comprehensive review of applications that minimizes emphasis on USMLE step 1 scores substantially reduced the difference between the percentages of URMs and those of other racial backgrounds who were offered interviews for a Neurology residency.

Bacterial mutagenicity screening in the pharmaceutical industry.

Genetic toxicity testing is used as an early surrogate for carcinogenicity testing. Genetic toxicity testing is also required by regulatory agencies to be conducted prior to initiation of first in human clinical trials and subsequent marketing for most small molecule pharmaceutical compounds. To reduce the chances of advancing mutagenic pharmaceutical candidates through the drug discovery and development processes, companies have focused on developing testing strategies to maximize hazard identification while minimizing resource expenditure due to late stage attrition. With a large number of testing options, consensus has not been reached on the best mutagenicity platform to use or on the best time to use a specific test to aid in the selection of drug candidates for development. Most companies use a process in which compounds are initially screened for mutagenicity early in drug development using tests that require only a few milligrams of compound and then follow those studies up with a more robust mutagenicity test prior to selecting a compound for full development. This review summarizes the current applications of bacterial mutagenicity assays utilized by pharmaceutical companies in early and late discovery programs. The initial impetus for this review was derived from a workshop on bacterial mutagenicity screening in the pharmaceutical industry presented at the 40th Annual Environmental Mutagen Society Meeting held in St. Louis, MO in October, 2009. However, included in this review are succinct summaries of use and interpretation of genetic toxicity assays, several mutagenicity assays that were not presented at the meeting, and updates to testing strategies resulting in current state-of the art description of best practices. In addition, here we discuss the advantages and liabilities of many broadly used mutagenicity screening platforms and strategies used by pharmaceutical companies. The sensitivity and specificity of these early mutagenicity screening assays using proprietary compounds and their concordance (predictivity) with the regulatory bacterial mutation test are discussed.

Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation.

We report on a retrospective analysis examining the influence of pre-transplant serum ferritin on transplant outcomes of 99 MDS patients receiving reduced intensity conditioning (RIC) HSCT. The median pre-transplant ferritin value was 1992 ng/ml (range: 6-9580 ng/ml). No patients received iron chelation therapy preceding transplantation. On univariate analysis, there was a strong correlation between a higher pre-transplant serum ferritin (>1500 ng/ml) and a significantly inferior 3-year OS (64.6+/-7.5% vs 39.6+/-7.3%, p=0.01). However, pre-transplant serum ferritin did not influence 3-year TRM (20.2+/-7% vs 27.4+/-7%, p=0.24). There was no difference in infection-related mortality, and incidence of acute or chronic GvHD between cohorts. On multivariate analysis, a raised serum ferritin (HR: 2.00, 95% CI: 0.97-3.57, p=0.03), and the presence of >5% bone marrow blasts at time of transplantation (HR: 2.14, 95% CI: 0.84-4.58, p=0.06) were independent predictors of an inferior overall survival. However, pre-transplant serum ferritin was not a significant predictor of disease-free survival, relapse or TRM. When compared with myeloablative regimens, RIC regimens may attenuate the impact of iron overload related end-organ toxicity. Prospective studies incorporating alternative biomarkers of iron metabolism alongside serum ferritin levels are needed to improve our understanding of the significance of iron overload in MDS patients undergoing allogeneic transplantation.