Unlocking the potential of drug-drug cocrystals - A comprehensive review.

Intensive research subjected to the improvement of solubility and bioavailability of certain drugs has popularized the formation of cocrystals, wherein the desired drug is non-ionically bonded to a coformer by means of weak bonds. This paper addresses how crystal engineering of two compatible drug components can enhance the physicochemical and therapeutic properties of either or both of the drugs, resulting in drug-drug cocrystals, with pertinent examples. The paper also discusses the continuous screening processes which are replacing the traditional methods of crystallization due to numerous benefits to the producer as well as the products. Although faced with certain regulatory and scale-up constraints, cocrystals provide immense opportunities to the field of novel drug development.

The Feasibility of Blinding Residency Programs to USMLE Step 1 Scores During GME Application, Interview, and Match Processes.

BACKGROUND: With the recent announcement that Step 1 score reporting will soon change to pass/fail, residency programs will need to reconsider their recruitment processes. OBJECTIVE: We (1) evaluated the feasibility of blinding residency programs to applicants' Step 1 scores and their number of attempts throughout the recruitment process; (2) described the selection process that resulted from the blinding; and (3) reviewed if a program's initial rank list, created before scores were known, would be changed before submission for the Match. METHODS: During the 2018-2019 and 2019-2020 recruitment seasons, all programs at a single sponsoring institution were invited to develop selection criteria in the absence of Step 1 data, and to remain blinded to this data throughout recruitment. Participating programs were surveyed to determine factors affecting feasibility and metrics used for residency selection. Once unblinded to Step 1 scores, programs had the option to change their initial rank lists. RESULTS: Of 24 residency programs, 4 participated (17%) in the first year: emergency medicine, neurology, pediatrics, and psychiatry. The second year had the same participants, with the addition of family and community medicine and radiation oncology (n = 6, 25%). Each program was able to determine mission-specific qualities in the absence of Step 1 data. In both years, one program made changes to the final rank list. CONCLUSIONS: It was feasible for programs to establish metrics for residency recruitment in the absence of Step 1 data, and most programs made no changes to final rank lists after Step 1 scores were known.

Therapeutic Monoclonal Antibodies Targeting Immune Checkpoints for the Treatment of Solid Tumors.

Recently, modulation of immune checkpoints has risen to prominence as a means to treat a number of solid malignancies, given the durable response seen in many patients and improved side effect profile compared to conventional chemotherapeutic agents. Several classes of immune checkpoint modulators have been developed. Here, we review current monoclonal antibodies directed against immune checkpoints that are employed in practice today. We discuss the history, mechanism, indications, and clinical data for each class of therapies. Furthermore, we review the challenges to durable tumor responses that are seen in some patients and discuss possible interventions to circumvent these barriers.