Preference for opioids in emergency department patients with acute musculoskeletal pain.

BACKGROUND: Public awareness of the opioid epidemic is increasing nationally, emphasizing the need to develop methods to reduce opioid use. We determined patient preference for analgesics before and after a brief educational intervention informing them of the risks and benefits of opioids versus non-steroidal anti-inflammatory drugs (NSAID's). We hypothesized 50% of patients would prefer opioids pre-intervention and that this would be reduced by the intervention by at least 15%. METHODS: Study Design-Before and after study. Setting-Suburban ED with annual census of 110,000. Patients-English-speaking adult ED patients with acute musculoskeletal pain. Interventions-An anonymous survey was administered by an investigator not involved in the patient's clinical care prior to physician evaluation, before and after a video describing the risks and benefits of opioids versus NSAID's. Patients were asked if they desired analgesics. Data Analysis-Descriptive statistics were used to summarize the data. Univariate analysis and logistic regression were used to predict patient demographics and pain characteristics associated with desire for analgesics. RESULTS: Of all 94 patients, 48 (51% [95% CI 41-62%]) desired an analgesic pre-intervention. Of these 48 patients, 10 (11% [5-19%]) specifically preferred an opioid. Of the 10 patients who preferred an opioid pre-intervention, one had no preference for analgesic post-intervention. CONCLUSIONS: Many adult ED patients with acute musculoskeletal pain do not desire any analgesics and few specifically prefer opioids. This knowledge can prove helpful to ED physicians across the country in discussing pain management options with patients as we attempt to combat the opioid epidemic.

Synthesis and Preclinical Evaluation of a Highly Improved Anticancer Prodrug Activated by Histone Deacetylases and Cathepsin L.

Lack of absolute selectivity against cancer cells is a major limitation for current cancer therapies. In the previous study, we developed a prodrug strategy for selective cancer therapy using a masked cytotoxic agent puromycin [Boc-Lys(Ac)-Puromycin], which can be sequentially activated by histone deacetylases (HDACs) and cathepsin L (CTSL) to kill cancer cells expressing high levels of both enzymes. Despite the promise as a selective cancer therapy, its requirement of relatively high dosage could be a potential issue in the clinical setting. To address this issue, we aimed to further improve the overall efficacy of our prodrug strategy. Since the proteolytic cleavage by CTSL is the rate-limiting step for the drug activation, we sought to improve the substrate structure for CTSL activity by modifying the α-amino protecting group of lysine. Here we show that protection with Fmoc [Fmoc-Lys(Ac)-Puromycin] exhibits a marked improvement in overall anticancer efficacy compared to the original Boc-Lys(Ac)-Puromycin and this is mainly due to the highly efficient cellular uptake besides its improved substrate structure. Furthermore, to address a concern that the improved drug efficacy might direct high toxicity to the normal cells, we confirmed that Fmoc-Lys(Ac)-Puromycin still retains excellent cancer selectivity in vitro and no obvious systemic off-target toxicity in vivo. Thus our preclinical evaluation data presented here demonstrate that the Fmoc-Lys(Ac)-Puromycin exhibits substantially improved anticancer efficacy, further supporting our approach for the selective cancer therapy.