Opioid ordering habits in the acute emergency department visit: Before and after implementation of departmental prescribing guidelines.

OBJECTIVE: At our emergency department (ED), opioid prescribing guidelines were implemented in September 2016. The opioid prescribing guidelines were adopted and revised from collective efforts and advocacy of the Michigan College of Emergency Physicians for ED-led opioid stewardship. We performed a retrospective before and after study to determine if opioid prescribing guidelines would change the use of intravenous opioids per patient and the morphine equivalent units (MEU) per patient in a suburban academic ED. METHODS: A retrospective observational study was conducted at a tertiary care level 1 trauma center with an annual ED volume of ≈ 130,000 visits. All intravenous orders of fentanyl, morphine, and hydromorphone for adult patients from January 1, 2015, through December 31, 2017, were tabulated. A 3-month (August 2016-October 2016) washout period was used. Poisson and ordinary linear regression analyses were employed to evaluate any difference in number of intravenous opioids ordered before and after adoption of the guidelines. Within our opioid prescribing guidelines was also guidance for oral opioid orders within the ED and oral opioid prescriptions for discharge, although these elements were not included in this investigation. RESULTS: A total of 108,327 intravenous opioid orders were included in the final analysis. After adoption of the opioid prescribing guidelines, the expected number of intravenous opioids ordered dropped by 3.1% (eß, 0.969; 95% confidence interval [CI], 0.779-1.209), and there was an additional decrease of 0.1% per month (eß, 0.999; 95% CI, 0.990-1.010). After the adoption of opioid prescribing guidelines, the average MEU dropped by 0.3 mg (95% CI, -0.47 to -0.13), and there was decrease of 0.01 mg per month (95% CI, -0.02 to -0.004). CONCLUSION: After the adoption of opioid prescribing guidelines, our analysis suggests that opioid prescribing guidelines are associated with clinically small but statistically significant changes in MEU ordered in ED. We cannot determine if this represented a continued trend of decreased opioid use or associated with the opioid prescribing guidelines.

Under-recognized Etiology of Altered Mental Status in a Patient with Alcoholism.

Wernicke's encephalopathy is an important condition for the emergency physician (EP) to consider in patients at risk for malnutrition. A 60-year-old man with history of alcoholism presented with word-finding difficulties, dysmetria, ataxia, and personality changes. After treatment with high-dose thiamine, his neurological status returned to his baseline. Although EPs routinely prescribe thiamine for patients with alcoholism, the common initial dose of 100 mg per day is likely subtherapeutic, and the population of patients at risk for malnutrition is much broader than only those with alcoholism, and includes those with cancer, anorexia nervosa, hyperemesis gravidarum, and others. EPs must be aware of this low-cost, readily available prophylaxis to prevent long-term neurological morbidity.

Structure-function relationships in human testis-determining factor SRY: an aromatic buttress underlies the specific DNA-bending surface of a high mobility group (HMG) box.

Human testis determination is initiated by SRY, a Y-encoded architectural transcription factor. Mutations in SRY cause 46 XY gonadal dysgenesis with female somatic phenotype (Swyer syndrome) and confer a high risk of malignancy (gonadoblastoma). Such mutations cluster in the SRY high mobility group (HMG) box, a conserved motif of specific DNA binding and bending. To explore structure-function relationships, we constructed all possible substitutions at a site of clinical mutation (W70L). Our studies thus focused on a core aromatic residue (position 15 of the consensus HMG box) that is invariant among SRY-related HMG box transcription factors (the SOX family) and conserved as aromatic (Phe or Tyr) among other sequence-specific boxes. In a yeast one-hybrid system sensitive to specific SRY-DNA binding, the variant domains exhibited reduced (Phe and Tyr) or absent activity (the remaining 17 substitutions). Representative nonpolar variants with partial or absent activity (Tyr, Phe, Leu, and Ala in order of decreasing side-chain volume) were chosen for study in vitro and in mammalian cell culture. The clinical mutation (Leu) was found to markedly impair multiple biochemical and cellular activities as respectively probed through the following: (i) in vitro assays of specific DNA binding and protein stability, and (ii) cell culture-based assays of proteosomal degradation, nuclear import, enhancer DNA occupancy, and SRY-dependent transcriptional activation. Surprisingly, however, DNA bending is robust to this or the related Ala substitution that profoundly impairs box stability. Together, our findings demonstrate that the folding, trafficking, and gene-regulatory function of SRY requires an invariant aromatic "buttress" beneath its specific DNA-bending surface.