Solvent-dependent photophysics of a red-shifted, biocompatible coumarin photocage.

Controlling the activity of biomolecules with light-triggered photocages is an important research tool in the life sciences. We describe here a coumarin photocage that unusually combines the biocompatible optical properties of strong absorption at a long wavelength close to 500 nm and high photolysis quantum yields. The favourable properties are achieved by synthetically installing on the photocage scaffold a diethyl amino styryl moiety and a thionoester group rather than the lactone typical for coumarins. The photocage's photophysics are analysed with microsecond transient absorption spectroscopy to reveal the nature of the excited state in the photolysis pathway. The excited state is found to be strongly dependent on solvent polarity with a triplet state formed in DMSO and a charge-separated state in water that is likely due to aggregation. A long triplet lifetime is also correlated with a high photolysis quantum yield. Our study on the biocompatible photocage reveals fundamental insight for designing advanced photocages such as longer wavelengths in different solvent conditions tailored for applications in basic and applied research.

A Photo-responsive Small-Molecule Approach for the Opto-epigenetic Modulation of DNA Methylation.

Controlling the functional dynamics of DNA within living cells is essential in biomedical research. Epigenetic modifications such as DNA methylation play a key role in this endeavour. DNA methylation can be controlled by genetic means. Yet there are few chemical tools available for the spatial and temporal modulation of this modification. Herein, we present a small-molecule approach to modulate DNA methylation with light. The strategy uses a photo-tuneable version of a clinically used drug (5-aza-2'-deoxycytidine) to alter the catalytic activity of DNA methyltransferases, the enzymes that methylate DNA. After uptake by cells, the photo-regulated molecule can be light-controlled to reduce genome-wide DNA methylation levels in proliferating cells. The chemical tool complements genetic, biochemical, and pharmacological approaches to study the role of DNA methylation in biology and medicine.

A Quality Assessment of a Collaborative Model of a Pediatric Antimicrobial Stewardship Program.

BACKGROUND: Infectious Diseases Society of America guidelines recommend that key antimicrobial stewardship program (ASP) personnel include an infectious disease (ID) physician leader and dedicated ID-trained clinical pharmacist. Limited resources prompted development of an alternative model by using ID physicians and service-based clinical pharmacists at a pediatric hospital. The aim of this study was to analyze the effectiveness and impact of this alternative ASP model. METHODS: The collaborative ASP model incorporated key strategies of education, antimicrobial restriction, day 3 audits, and practice guidelines. High-use and/or high-cost antimicrobial agents were chosen with audits targeting vancomycin, caspofungin, and meropenem. The electronic medical record was used to identify patients requiring day 3 audits and to communicate ASP recommendations. Segmented regression analyses were used to analyze quarterly antimicrobial agent prescription data for the institution and selected services over time. RESULTS: Initiation of ASP and day 3 auditing was associated with blunting of a preexisting increasing trend for caspofungin drug starts and use and a significant downward trend for vancomycin drug starts (relative change -12%) and use (-25%), with the largest reduction in critical care areas. Although meropenem use was already low due to preexisting requirements for preauthorization, a decline in drug use (-31%, P = .021) and a nonsignificant decline in drug starts (-21%, P = .067) were noted. A 3-month review of acceptance of ASP recommendations found rates of 90%, 93%, and 100% for vancomycin, caspofungin, and meropenem, respectively. CONCLUSIONS: This nontraditional ASP model significantly reduced targeted drug usage demonstrating acceptance of integration of service-based clinical pharmacists and ID consultants.

Implementation of a standardized process for ordering and dispensing of high-alert emergency medication infusions.

OBJECTIVES: Pharmacies encounter challenges when ensuring safe, timely medication dispensing to patients in the pediatric intensive care unit, when high-alert medications are needed in emergent situations. Removal of these medications from nursing stock presented challenges to providing timely administration to critical patients. The project's purpose was to develop a new method for reducing dispensing time while improving patient safety in pediatric intensive care units. METHODS: A committee of physicians, nurses, a clinical pharmacist, and pharmacy administration collaborated for process development. The process established a list of compounded, ready-to-use infusions stored in the pharmacy, immediately available for dispensing. The dispensing mechanism includes ordering and dispensing processes using an "Urgent Drip Request" form. Most frequently ordered infusions (dopamine, epinephrine, norepinephrine) were added to automated dispensing cabinets in critical care units in concentrations that could be safely infused centrally or peripherally. RESULTS: During the initial 4 months, 71 "Urgent Drip Request" sheets were processed. Drug utilization evaluation demonstrated a dispensing time of less than 1 minute for drip medications leaving the pharmacy after the form was received. No sheets processed exceeded the institutional 30-minute turnaround time, nor were errors or delays documented. Limited turnaround time data existed preimplementation but was not robust enough for analysis. It was not ethically feasible to perform a head-to-head comparison with the previous method, as it might have resulted in delay of therapy and negative patient outcomes. CONCLUSIONS: This program allows high-alert medication infusion availability in an expedited manner, removes potential for compounding errors at the bedside, and assures clean room preparation. This has improved pharmacy efficiency in provision of safe patient care to critically ill pediatric patients.