A Bayesian approach to aid in formulary decision making: incorporating institution-specific cost-effectiveness data with clinical trial results.

Pharmacy and therapeutics committees commonly cite a lack of generalizability as a reason for not incorporating cost-effectiveness information into decision making. To address this concern, many committees undertake site-specific economic evaluations, which are often limited by small sample sizes and nonrandomized designs. We show how 2 complementary approaches were used to minimize these limitations in an economic evaluation of abciximab at 1 institution. Using a propensity score methodology, we selected patients who did not receive abciximab for the comparison cohort. Then, we adopted a Bayesian, hierarchical, random-effects model to integrate site-specific and clinical trial data. We applied the posterior distributions of effectiveness with local cost data in a traditional decision-analytic model. In 74% of the simulations, abciximab was cost-effective at 1 institution at the $50,000 per life year saved threshold, assuming a 50:50 split of patients undergoing coronary stenting and angioplasty. Among patients undergoing coronary stenting, the cost-effectiveness ratio of the addition of abciximab was at or below the $50,000 per life year saved threshold in 66.0% of the simulations.     

Multiple connexins confer distinct regulatory and conductance properties of gap junctions in developing heart.

Multiple gap junction proteins (connexins) and channels have been identified in developing and adult heart. Functional expression of the three connexins found in chick heart (connexin42, connexin43, and connexin45) by stable transfection of communication-deficient neuro2A (N2A) cells revealed that all three connexin cDNAs are capable of forming physiologically distinct gap junctions that differ in their transjunctional voltage dependence and unitary channel conductances. The transjunctional voltage dependences of connexin45 and connexin42 closely resembled those of 4-day and 18-day embryonic chick heart gap junctions, respectively. The multiple channel conductances between 80 and 240 pS, including the predominant 160 pS channel, observed in embryonic chick heart were also common to connexin42. The expression of multiple gap junction channels with distinct conductance and regulatory properties within a given tissue may account for developmental changes in intercellular communication.     

A clinical librarian program in the intensive care unit.

OBJECTIVES: Clinical decision-making in the intensive care setting frequently requires the physician to obtain additional resource information. Physicians typically consult with colleagues, use personal medical books or files, or use library materials. Clinical librarians may also be used. This study evaluates the effectiveness of an ongoing clinical librarian program in the intensive care setting. DESIGN/SETTING: During a 3-month period, house officers in the medical and coronary ICUs in a major teaching hospital asked the clinical librarian 66 patient-care questions. Attached to the information selected by the clinical librarian was a questionnaire asking how the information was applied. MAIN RESULTS: There was an overall response rate of 65.1%. House officers indicated that the information: a) aided in diagnosis (37.2%), b) contributed to a better understanding of the therapy (51.2%), and c) resulted in improved patient management (30.2%). In some instances, the information was multibeneficial. The clinical librarian spent an average of 47 mins/question, and accumulated an average computer charge of $3.59. Personnel and on-line charges over the 3-month study period averaged $45/question. CONCLUSIONS: Clinical librarian programs may deliver patient-specific information in a timely, cost-effective manner. This information has an impact in the intensive care setting.     

Immunocytochemical demonstration of vertebrate peptides in invertebrates: the homology concept

During the last years many positive immunocytochemical reactions have been described in invertebrates using antisera to vertebrate regulatory peptides. However, due to the specificity problems associated with immunocytochemistry, the significance of the majority of these findings remains unclear, as so far only a few of the substances causing the immunoreactions in invertebrates have been isolated. It is proposed that comparing the localizations of "vertebrate" peptides in different and not closely related species of an invertebrate group may give a clue to the physiological relevance of the immunoreactive substances.     

The use of urine proteomic and metabonomic patterns for the diagnosis of interstitial cystitis and bacterial cystitis

The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC). The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS) and high-resolution proton nuclear magnetic resonance (1H-NMR) spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC). We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping) as a fitness test for a supervised system (a genetic algorithm). With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%.     

Generation and characterization of a clonotypic antibody specific for the T cell receptor of an arthritogenic T cell clone--studies in adjuvant arthritis

Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clone (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HSP60 176-190. Furthermore, a crucial role for T cells with HSP60 176-190 specificity in AA was shown by induction of tolerance using HSP60 176-190 or by immunization with an altered peptide ligand based on the same sequence. To study clonal expansion of A2b-like T cells during AA and to determine their role in AA induction, we generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell clone (TCR AV11S1/BV18). This antibody stained A2b T cells in flow cytometry experiments, induced proliferation of A2b cells when fixed on a solid support, and inhibited antigen-induced A2b proliferation when added in solution. A2b-like T cells were detected in a low frequency in lymphoid organs of arthritic rats. Thus, as in vivo administration of 16C4 did not inhibit AA, cells containing the determinant recognized by 16C4 are possibly not the sole contributors to AA development. Furthermore, epitope specific interventions by antigen administration may be possible even in cases where the epitope specific T cell clonotype is of low frequency.     

Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.