Faculty Bibliography

We report a case of a 29-year-old man who presented with intermittent haemoptysis for about 18 months. Previously, his symptoms had been diagnosed as musculoskeletal pain and later as pneumonia. CT found a venous infarct in the right lung in addition to extensive lymphadenopathy in the mediastinum and pulmonary hila, with associated calcifications almost completely occluding the superior vena cava and azygos vein. Further questioning revealed that the patient had once worked on an organic farm in Colorado. Subsequent work up was positive for histoplasmosis yeast antibodies. The patient was diagnosed with fibrosing mediastinitis (FM) and started on itraconazole for 3 months. We note that FM is a rare complication of histoplasmosis and can present as chronic haemoptysis. Travel history is an important aspect of the clinical evaluation. Antifungal agents have shown some efficacy in treating histoplasmosis-related FM.

BACKGROUND: Hospital care on weekends has been associated with delays in care, reduced quality, and poor clinical outcomes. OBJECTIVE: The purpose of this study was to evaluate the impact of a weekend hospital intervention on processes of care and clinical outcomes. The multifaceted intervention included expanded weekend diagnostic services, improved weekend discharge processes, and increased physician and care management services on weekends. DESIGN AND PATIENTS: This was an interrupted time series observational study of adult non-obstetric patients hospitalized at a single academic medical center between January 2011 and January 2014. The study included 18 months prior to and 19 months following the implementation of the intervention. Data were analyzed using segmented regression analysis with adjustment for confounders. MAIN MEASURES: The primary outcome was average length of stay. Secondary outcomes included percent of patients discharged on weekends, 30-day readmission rate, and in-hospital mortality rate. KEY RESULTS: The study included 57,163 hospitalizations. Following implementation of the intervention, average length of stay decreased by 13 % (95 % CI 10-15 %) and continued to decrease by 1 % (95 % CI 1-2 %) per month as compared to the underlying time trend. The proportion of weekend discharges increased by 12 % (95 % CI 2-22 %) at the time of the intervention and continued to increase by 2 % (95 % CI 1-3 %) per month thereafter. The intervention had no impact on readmissions or mortality. During the post-implementation period, the hospital was evacuated and closed for 2 months due to damage from Hurricane Sandy, and a new hospital-wide electronic health record was introduced. The contributions of these events to our findings are not known. We observed a lower inpatient census and found differences in patient characteristics, including higher rates of Medicaid insurance and comorbidities, in the post-Hurricane Sandy period as compared to the pre-Sandy period. CONCLUSIONS: The intervention was associated with a reduction in length of stay and an increase in weekend discharges. Our longitudinal study also illuminated the challenges of evaluating the effectiveness of a large-scale intervention in a real-world hospital setting.

BACKGROUND: Late afternoon hospital discharges are thought to contribute to admission bottlenecks. We previously described an intervention that resulted in a statistically significant increase in the discharge before noon (DBN) rate on 2 inpatient medicine units. OBJECTIVE: To evaluate (1) the effect of an increased DBN rate on the admission arrival time and the number of admissions per hour and (2) the sustainability of our DBN initiative. DESIGN: Pre-/postintervention retrospective analysis. SETTING: Two acute-care inpatient medicine units in a tertiary care, urban, academic medical center. PATIENTS: For the admission arrival time and admissions per hour analysis, all inpatients admitted to the medical units from June 1, 2011 to June 31, 2013. For the sustainability analysis, all patients discharged from July 1, 2013 to December 31, 2014. INTERVENTION: A multidisciplinary intervention to increase the DBN rate. MEASUREMENTS: Date and time of arrival to all inpatient sites, and discharge date and time of all patients from 2 inpatient medicine units. RESULTS: Concurrent with our increase in DBN rate, we found a statistically significant change in the median arrival time of emergency department (ED) admissions and transfers from 5 pm to 4 pm. High-frequency admission peaks were statistically significantly reduced for ED admissions. The statistically significant increase in DBN rate is sustained at 35%. CONCLUSIONS: Increasing the DBN rate correlates with admissions arriving earlier in the day and reductions in high-frequency peaks of ED admissions. Statistically significant improvements in DBN rates are sustainable. Journal of Hospital Medicine 2015. (c) 2015 Society of Hospital Medicine.

A 49-year-old woman with cholangiocarcinoma metastatic to the lungs presented with new-onset unrelenting headaches. A lumbar puncture revealed malignant cells consistent with leptomeningeal metastasis from her cholangiocarcinoma. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal enhancement. An intrathecal (IT) catheter was placed and IT chemotherapy was initiated with methotrexate. Her case is notable for the rarity of cholangiocarcinoma spread to the leptomeninges, the use of IT chemotherapy with cytologic and potentially symptomatic response, and a possible survival benefit in comparison to previously reported cases of leptomeningeal carcinomatosis secondary to cholangiocarcinoma.

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