Rifaximin Is Effective for the Treatment of Clostridium difficile-Associated Diarrhea: Results of an Open-Label Pilot Study.

Objectives. This open-label trial assessed the efficacy and safety of rifaximin as first-line therapy in hospitalized patients with Clostridium difficile-associated diarrhea (CDAD). Methods. We enrolled thirteen patients who had a confirmed diagnosis of CDAD characterized by ≥3 unformed stools/day and positive C. difficile toxin assay. Those patients received rifaximin 400 mg three times daily for 10 days. Resolution of symptoms, repeat assay 10 days after treatment, and followup for recurrence were assessed. Results. Eight patients completed the study, and all reported symptom resolution during treatment. Mean time to last unformed stool was 132 h ± 42.5 h. Seven patients had no relapse by week 2 and in longer followup (median 162 days). One patient had recurrent CDAD during a repeat hospitalization. Conclusions. Rifaximin was effective and safe as first-line treatment for CDAD and did not result in recurrence in most patients.

Mechanisms of oxidant production in esophageal squamous cell and Barrett's cell lines.

We hypothesized that differences among individuals in reflux-induced oxidant production by esophageal squamous epithelial cells might contribute to the development of Barrett's esophagus. We studied the effects of acid and bile acids on the production of reactive oxygen species (ROS) in esophageal squamous cell lines derived from gastroesophageal reflux disease patients with (NES-B3T) and without (NES-G2T) Barrett's esophagus and in a Barrett's epithelial cell line (BAR-T). Cells were incubated with an ROS-sensitive probe and exposed to acidic medium, neutral bile acid medium, or acidic bile acid medium. ROS were quantified in the presence and absence of diphenyleneiodonium chloride (DPI, an NADPH oxidase inhibitor), N(G)-monomethyl-l-arginine (l-NMMA, a nitric oxide synthase inhibitor), and rotenone (a mitochondrial electron transport chain inhibitor). Acidic bile acid medium induced ROS production in both squamous cell lines; however, only DPI blocked ROS production by NES-B3T cells, whereas both DPI and l-NMMA blocked ROS production by NES-G2T cells. In BAR-T cells, acidic medium and acidic bile acid medium induced the production of ROS; l-NMMA prevented ROS production after exposure to acidic medium, whereas ROS production induced by acidic bile acid medium was blocked by DPI. These studies demonstrate that there are differences between esophageal squamous cells and Barrett's epithelial cells and between esophageal squamous cells from gastroesophageal reflux disease patients with and without Barrett's esophagus in the mechanisms of oxidant production induced by exposure to acid and bile acids.

Pharmacoeconomic considerations for inflammatory bowel disease in the era of biological therapies.

The biological therapies have revolutionized the ability to treat patients with inflammatory bowel disease. While these therapies have proven efficacy, they are not without significant medication expense. This has raised the question of whether society can afford these new therapies. Costs associated with inflammatory bowel disease have focused traditionally on direct costs of disease, with the greatest contributions due to surgeries and hospitalization. Initial investigations suggest that biologics can reduce healthcare utilization and their associated costs. Additionally, the importance of indirect costs and improvements in quality of life must also be considered when examining the cost efficiency of these new therapeutic modalities, which may result in a cost savings for our healthcare system.

Economics of the use of biologics in the treatment of inflammatory bowel disease.

The introduction of the biologic therapies into the therapeutic regiment for IBD, coupled with the vast changes seen in health care delivery within the past decade, have turned previous economic assumptions and models on their head, and opened up a new opportunity to redefine what is truly the cost of a disease, and of its' interventions. Pundits and pencil-pushers are quick to point to the high drug cost as a threat to the economic stability of the health care system, without first doing a carefully planned, balanced analysis of the overall impact that such a therapy will make on the entire cost-structure of the system. This is also true outside of the United States, where those who must budget and pay for the therapies do not pay for the use of health care services, and simply enter the drug costs on an accountant's debit sheet. Such analyses are complicated, because they must calculate the impact that such therapies have on the direct costs of health care and the indirect costs for both the patient and their families or health care support system. Realizing what impact these therapies might have on altering the natural history of these previously relentless chronic debilitating conditions, and redefining how normal quality of life can actually get on these therapies, should be the focus of future studies as clinicians try to calculate truly whether these agents are cost savings for society overall.

Efficacy and safety of fast-track recovery strategy for patients undergoing laparoscopic nephrectomy.

BACKGROUND AND PURPOSE: Factors that adversely affect early recovery after major laparoscopic procedures include ileus, pain, nausea, emesis, and fatigue. The objective of this randomized controlled study was to evaluate the impact of a multimodal fast-track (FT) rehabilitation program on recovery and length of hospital stay after laparoscopic nephrectomy. PATIENTS AND METHODS: Thirty patients undergoing laparoscopic nephrectomy received either conventional care (control) or an FT recovery program. All patients received a standardized anesthetic technique and patient- controlled analgesia (morphine) for postoperative pain control. In the FT group, patients received premedication with rofecoxib and ranitidine, local anesthesia was administered at the ports and renal fosa during surgery, and postoperative non-opioid analgesic and gastrokinetic drugs were administered as part of an early enteral nutrition and mobilization program. During the postoperative period, pain and nausea were assessed at specific time intervals. In addition, recovery room and hospital discharge times, the need for rescue analgesics and antiemetics, patient satisfaction with pain management and quality of recovery, and side effects were recorded daily for 3 days after surgery. Patients were discharged home when they met previously defined discharge criteria. RESULTS: The FT group was discharged earlier from the recovery room (74+/-23 v 103+/-47 minutes) and the hospital (41+/-11 v 59+/-11 hours). Pain and nausea scores were consistently lower in the FT group during the first 48 hours after surgery. In addition, the requirement for antiemetic rescue therapy during the first 24 hours was reduced in the FT group (15% v 58%). The FT group also received less morphine during the first 2 postoperative days (14+/-16 v 40+/-24 mg). Finally, patient satisfaction with postoperative pain control was significantly higher in the FT group. CONCLUSIONS: A multimodal approach to minimizing postoperative side effects led to a reduced recovery room and hospital stay, as well as better pain control and patient satisfaction after laparoscopic nephrectomy.

The effect of cerebral monitoring on recovery after general anesthesia: a comparison of the auditory evoked potential and bispectral index devices with standard clinical practice.

UNLABELLED: The use of cerebral monitoring may improve the ability of anesthesiologists to titrate anesthetic drugs. However, there is controversy regarding the impact of the alleged anesthetic-sparing effects of cerebral monitoring on the recovery process and patient outcome. We designed this prospective double-blinded, sham-controlled study to evaluate the impact of intraoperative monitoring with the electroencephalogram bispectral index (BIS) or auditory evoked potential (AEP) device on the usage of desflurane and the time to discharge from the recovery room, as well as on patient satisfaction with their anesthetic experience and recovery. Ninety healthy patients undergoing laparoscopic general surgery procedures using a standardized anesthetic technique were randomly assigned to one of three monitoring groups: standard clinical practice (control), BIS-guided, or AEP-guided. Both the BIS and AEP monitors were connected to all patients before induction of general anesthesia. In the control group, the anesthesiologists were not permitted to observe the BIS or AEP index values during the intraoperative period. In the BIS-guided group, the volatile anesthetic was titrated to maintain a BIS value in the range of 45-55. In the AEP-guided group, the targeted AEP index range was 15-20. The BIS and AEP indices, as well as end-tidal desflurane concentration, were recorded at 3-5 min intervals. Recovery times to awakening, tracheal extubation, fast-track score >or=12, and postanesthesia care unit (PACU) discharge criteria were recorded at 1-10 min intervals. In addition, patient satisfaction with anesthesia and quality of recovery were evaluated on 100- and 18-point scales, respectively, at 24 h after surgery. The AEP- and BIS-guided groups were administered significantly smaller average end-tidal desflurane concentrations than the control group (3.8 +/- 0.9 and 3.9 +/- 0.6 versus 4.7 +/- 1.7, respectively) (P < 0.01). Although the emergence times to eye opening, tracheal extubation, and obeying commands were consistently shorter in the AEP and BIS groups (6 +/- 4 and 6 +/- 5 versus 8 +/- 8 min; 6 +/- 5 and 6 +/- 4 versus 11 +/- 10 min; and 8 +/- 4 and 7 +/- 4 versus 12 +/- 9 min, respectively), only the extubation times were significantly different from the control group (P < 0.05). More importantly, the length of the PACU stay was significantly shorter in both the AEP- and BIS-guided groups (79 +/- 43 and 80 +/- 47 versus 108 +/- 58 min, respectively) (P < 0.05). The patients' quality of recovery was also significantly higher in the two monitored groups (15 +/- 2 versus 13 +/- 3 in the control group, P < 0.05). We concluded that cerebral monitoring with either the BIS or AEP devices reduced the maintenance anesthetic (desflurane) requirement, resulting in a shorter length of stay in the PACU and improved quality of recovery after laparoscopic surgery. However, there were no significant outcome differences between the two cerebral monitored groups. IMPLICATIONS: Compared with standard monitoring practices, use of an auditory evoked potential or bispectral index monitor to titrate the volatile anesthetic led to a significant reduction in the anesthetic requirement. The anesthetic-sparing effect of cerebral monitoring resulted in a shorter postanesthesia care unit stay and improved quality of recovery from the patient's perspective.