Alternative Donor Hematopoietic Cell Transplantation Conditioned With Myeloablative Busulfan, Fludarabine, and Melphalan is Well Tolerated and Effective Against High-risk Myeloid Malignancies.

Busulfan, fludarabine, and melphalan as hematopoietic cell transplant conditioning, was used in 6 patients aged 1 to 19 years with very high-risk myeloid malignancies. This dose regimen had an acceptable toxicity profile resulting in complete donor engraftment even following transplantation of small 2/6 antigen disparate umbilical cord blood grafts. It provided excellent disease control as all patients had high-risk features in terms of cytogenetics, therapy-related leukemia, and/or significant measurable disease before transplant. All patients remain in remission, without acute or chronic graft-versus-host disease with a median follow-up of 24 months. A larger study is indicated to confirm the efficacy and safety of this regimen.

Impact of a Dedicated Research Rotation during Ophthalmology Residency.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires that ophthalmology residents participate in scholarly activity during residency. However, residents lack protected time for research. OBJECTIVE: To determine the impact of a dedicated research rotation on scholarly productivity and research experience during residency. METHODS: This cohort study compared two groups of ophthalmology residents. Residents who graduated between 2004-2009 did not have dedicated research time and served as control residents (CR) while residents who graduated between 2010-2015 had a dedicated research rotation and served as the intervention group (research residents, RR). Primary outcomes included publications and presentations recorded over a four-year period, spanning the three years of residency and first year after graduation. These were analyzed by linear regression and t-tests. Residents also took surveys regarding research experience and chi squared tests and logistic regression were used to compare these results. RESULTS: The RR had 0.97 more publications and 1.3 more presentations compared to the CR after adjusting for PhD status, pre-residency publications and presentations, age at graduation, gender and race (p=0.09 and p=0.02, respectively). RR had higher odds of reporting adequate time to complete research (OR=13.11, 95% CI 3.58-48.03, p < 0.001) and satisfaction with their research experience (OR=6.96, 95% CI=2.104-23.053, p=0.002). CONCLUSIONS: Residents with a research rotation had more time to complete research, were more satisfied with their research experience, and generated more publications and presentations compared to residents without the research rotation. A research rotation can help meet ACGME requirements and help residents achieve greater scholarly activity.

Use of a physiologic bicarbonate buffer system for dissolution characterization of ionizable drugs.

PURPOSE: The aim of this study was to examine if sparging with CO2(g) could be used to establish stable biorelevant bicarbonate buffers, in aqueous medium, for use in dissolution characterization of low-solubility ionizable drugs. METHODS: Preparation of the bicarbonate-containing dissolution medium was monitored by use of a commercially available fiberoptic probe to measure the concentration of dissolved CO2(aq). Intrinsic dissolution measurements at 100 rpm, 37 degrees C for indomethacin and dipyridamole were performed using a rotating disk and UV detection at pH 6.8 and 5.0 in a USP dissolution vessel apparatus. RESULTS: Indomethacin dissolution at pH 6.8 was significantly impacted by the concentration of CO2(g) in the sparging gas. Dipyridamole flux at pH 6.8 was independent of buffer species or buffer concentrations studied. However, dipyridamole dissolution at pH 5 was also a strong function of the concentration of CO2(g) in the sparging gas. CONCLUSIONS: Stable bicarbonate biorelevant buffers could be established to perform intrinsic dissolution rate determinations for indomethacin and dipyridamole as long a continuous gas sparging of CO2(g) was used. Depending of the pH of the dissolution medium, the intrinsic dissolution rates of both indomethacin and dipyridamole were affected by the bicarbonate concentration. Sparging with CO2(g) to create physiologic buffers has a unique advantage over conventional buffers in that gas sparging serves as a continuous source of bicarbonate buffer species. This advantage was demonstrated by performing dissolution experiments at pH values typically associated with the fed state (pH 5) and applying relatively low CO2(g) pressures, resulting in bicarbonate concentrations less than 0.5 mM. It was demonstrated that CO2(g) sparging at a pH consistent with the fed state created an in-situ bicarbonate buffer at low concentrations, which had a significant impact on the dissolution of a basic drug such as dipyridamole.