Simulation of large-scale production of a soluble recombinant protein expressed in Escherichia coli using an intein-mediated purification system.

Inteins are self-cleavable proteins that under reducing conditions can be cleaved from a recombinant target protein. Industrially, an intein-based system could potentially reduce production costs of recombinant proteins by facilitating a highly selective affinity purification using an inexpensive substrate such as chitin. In this study, SuperPro Designer was used to simulate the large-scale recovery of a soluble recombinant protein expressed in Escherichia coli using an intein-mediated purification process based on the commercially available IMPACT system. The intein process was also compared with a conventional process simulated by SuperPro. The intein purification process initially simulated was significantly more expensive than the conventional process, primarily owing to the properties of the chitin resin and high reducing-agent (dithiothreitol [DTT]) raw material cost. The intein process was sensitive to the chitin resin binding capacity, cleavage efficiency of the intein fusion protein, the size of the target protein relative to the intein tag, and DTT costs. An optimized intein purification process considerably reduced costs by simulating an improved chitin resin and alternative reducing agents. Thus, to realize the full potential of intein purification processes, research is needed to improve the properties of chitin resin and to find alternative, inexpensive raw materials.

Nurse evaluation of a pain medication protocol in a selective postoperative population.

Postoperative pain in 33 patients who underwent radical prostatectomy was managed by an intramuscular nonsteroidal antiinflammatory drug protocol rather than by administration of narcotics. Patients rated their perception of pain with a visual analog scale on the first postoperative day both before and after receiving ketorolac tromethamine. The medication was effective in relieving pain after this major operation. Costs were approximately one half that of the traditional narcotic protocol used before this study.

Evaluation of the financial impact of ketorolac tromethamine therapy in hospitalized patients.

This retrospective cohort study aimed to determine the resource utilization and cost consequences of ketorolac tromethamine in postoperative pain management in a variety of clinical circumstances. All patients were treated at LDS Hospital, Salt Lake City, Utah, a 520-bed teaching hospital. A long-term archive of clinical and financial data from a computerized hospital information system was searched for patients with specified primary International Classification of Diseases, 9th Revision, Clinical Modification discharge diagnoses treated from June 1, 1990, to July 1, 1992, who received ketorolac (n = 229). These patients were matched with cohort patients (n = 821) treated from July 1, 1989, to May 31, 1990, who did not receive ketorolac. The archive contained information on ketorolac exposure as well as concurrent drug therapy and adverse drug events that had been prospectively evaluated during hospitalization throughout the study and cohort periods. Detailed costs were available for each patient. The study examined attributable differences in lengths of stay and total costs using linear regression modeling. We found a statistically significant attributable decreased length of stay for ketorolac patients of 1.15 days. Case patients also had reduced usage of narcotic drugs (4.39 fewer doses than cohorts and 15.6 hours shorter duration of narcotics than cohorts), reduced use of antiemetic and antipruritic medications, and reduced numbers of adverse events. Linear regression modeling showed that ketorolac use was significantly related to reduced cost using inflation-adjusted dollars. We believe that ketorolac has significant cost advantages over opiate analgesics because of its narcotic-sparing effects. Advantages of ketorolac use include reduced rates of adverse drug events, reduced lengths of stay, especially for orthopedic surgery, and reduced overall hospital costs for diagnosis-related groups associated with cholecystectomy.

Cost-effectiveness comparison of single and multiple-dose antibiotic treatment of lower uncomplicated urinary tract infections.

This study analyzed the cost-effectiveness of antibiotic treatments of different durations for acute cystitis in non-pregnant females. Questionnaires were sent to 400 practitioners evenly distributed throughout Italy. Data are reported from 2,069 patients. The clinical bacteriological efficacy at 10-15 days was 86.4% for single-dose treatment with fosfomycin-trometamol (FT), and 81.8% for the multiple-dose antibiotics group (MDAG). Disappearance of symptoms occurred in 2.1 days with FT and 3.4 days with MDAG. With FT 93.8% of patients were free of adverse events and 86.9% with MDAG. Analysis of the cost-effectiveness indicators for cure rate and absence of adverse events showed that treatment costs were similar for all antibiotics. FT needed less time interval for symptoms to disappear with a slightly higher cost than for MDAG, which had a better cost/effectiveness ratio.