Faculty Bibliography

BACKGROUND: Late afternoon hospital discharges are thought to contribute to admission bottlenecks, overcrowding, and increased length of stay (LOS). In January 2012, the discharge before noon (DBN) percentage on 2 medical units was 7%, below the organizational goal of 30%. OBJECTIVE: To sustainably achieve a DBN rate of 30% and to evaluate the effect of this intervention on observed-to-expected (O/E) LOS and 30-day readmission rate. DESIGN: Pre-/post-intervention retrospective analysis. SETTING: Two acute care inpatient medical units in an urban, academic medical center. PATIENTS: All inpatients discharged from the units. INTERVENTION: All staff helped create a checklist of daily responsibilities at a DBN kickoff event. We initiated afternoon interdisciplinary rounds to identify next-day DBNs and created a website for enhanced communication. We provided daily feedback on the DBN percentage, rewards for success, and real-time opportunities for case review. MEASUREMENTS: Calendar month DBN percentage, O/E LOS, and 30-day readmission rate. RESULTS: The DBN percentage increased from 11% in the 8-month baseline period to an average of 38% over the 13-month intervention (P = 0.0002). The average discharge time moved 1 hour and 31 minutes earlier in the day. The O/E LOS declined from 1.06 to 0.96 (P = 0.0001), and the 30-day readmission rate declined from 14.3% to 13.1% (P = 0.1902). CONCLUSIONS: Our study demonstrates that increased DBN is an achievable and sustainable goal for hospitals. Future work will allow for better understanding of the full effects of such an intervention on patient outcomes and hospital metrics. Journal of Hospital Medicine 2014;9:210-214. (c) 2014 Society of Hospital Medicine.

BACKGROUND: Electronic order-sets increasingly ask clinicians to answer questions or follow algorithms. Cooperation with such requests has not been studied. SETTING: Internal Medicine service of an academic medical center. OBJECTIVE: We studied the accuracy of clinician responses to questions embedded in electronic admission and discharge order-sets. Embedded questions asked whether any of three "core" diagnoses was present; a response was required to submit orders. Endorsement of any diagnosis made available best-practice ordering screens for that diagnosis. DESIGN: Three reviewers examined 180 electronic records (8% of discharges), drawn equally (for each core diagnosis) from possible combinations of Yes/No responses on admission and discharge. In addition to noting responses, we identified whether the core diagnosis was coded, determined from notes whether the admitting clinician believed that diagnosis present, and sought clinical evidence of disease on admission. We also surveyed participating clinicians anonymously about practices in answering embedded questions. MEASUREMENTS: We measured occurrence of six admission and five discharge scenarios relating medical record evidence of disease to clinician responses about its presence. RESULTS: The commonest discordant pattern between response and evidence was a negative response to disease presence on admission despite both early clinical evidence and documentation. Survey of study clinicians found that 75% endorsed some intentional inaccuracy; the commonest reason given was that questions were sometimes irrelevant to the clinical situation at the point asked. CONCLUSION: Through faults in order-set design, limitations of software, and/or because of an inherent tendency to resist directed behavior, clinicians may often ignore questions embedded in order-sets.

5-Fluorouracil (5-FU) is the most routinely administered drug in the treatment of colon cancer. The main mechanism of the drug is not completely understood and its method of administration has been strongly disputed. A 24-hour infusion of 5-FU has clinically yielded better response rates and lower toxicities in comparison to bolus administration, but an exploration into possible mechanisms needs to be performed. Experiments were conducted with two 5-FU resistant cell lines where cytotoxicity, thymidylate synthase (T.S.) activity, thymidine kinase (T.K.) activity, DNA and RNA incorporation, and T.S. expression were contrasted between a 10 microM/24 hour administration of 5-FU (simulating continuous exposure) and a 100 microM/1 hour schedule (simulating bolus administration). After 6 days from the initial exposure, the 10 microM/24 hour schedule (schedule A) inhibited more cell growth than the 100 microM/1 hour regimen (schedule B) by more than 38% and 17% in the two cell lines. After the 6-day observation, schedule A inhibited twice as much T.S. activity as schedule B. Incorporation of [14C]-5-FU into DNA and total RNA was higher in cells exposed to schedule A in comparison to schedule B over the 6 days. T.S. expression and T.K. activity patterns were variable over time. Thus, the exposure of 10 microM/24 hour 5-FU results in superior cytotoxicity when compared to a 100 microM/1 hour regimen and its effectiveness may be explained mechanistically by T.S. activity and DNA and RNA incorporation

The computer algorithm COMPARE provides information regarding the biological mechanism of action of a compound. In this study, excellent correlations were obtained for 2,2'-[3,3'-dimethoxy[1,1'-biphenyl]-4,4'-diyl)diimino]bis- benzoic acid (redoxal) and 1-(p-bromophenyl)-2-methyl-1H- naphth[2,3-d]imidazole-4,9-dione (BNID) and two well-studied dihydroorotate dehydrogenase (DHOD) inhibitors, dichloroallyl lawsone and brequinar, in terms of antiproliferative activity against tumor cell lines in vitro. When redoxal and BNID were incubated with MOLT-4 cells for 72 hr, 50% growth inhibition was achieved at 0.7 and 3.5 microM, respectively. After 24 hr of incubation, pyrimidine triphosphate pools were shown to be decreased by 50% by redoxal (1 microM) and BNID (0.25 microM). Addition of either uridine (50 microM) or cytidine (100 microM) antagonized the cellular cytotoxicity caused by either drug; uridine corrected the UTP and CTP deficit, whereas cytidine corrected only the CTP deficit. Exposure of MOLT-4 cells to a 1 microM concentration of either drug for 18 hr followed by a 1-hr exposure to [14C]bicarbonate showed a 97% decrease of incorporation of [14C] into pyrimidine triphosphates accompanied by a 91- and 82-fold increase in radioactive incorporation into L-dihydroorotate and N-carbamyl-L-aspartate, respectively. By direct exposure of DHOD prepared from MOLT-4 cell mitochondria to a range of concentrations of the two drugs, apparent Ki values of 0.33 microM (redoxal) and 0.53 microM (BNID) were determined. These data provide direct evidence for inhibition of DHOD by redoxal and BNID in MOLT-4 lymphoblasts