Impact of a vancomycin restriction policy on use and cost of vancomycin and incidence of vancomycin-resistant Enterococcus

OBJECTIVE: To review the appropriateness of vancomycin therapy, changes in vancomycin use, and the incidence of vancomycin-resistant Enterococcus (VRE) after implementation of a limited restriction policy requiring approval from the Infectious Diseases Approval service to continue vancomycin therapy beyond 72 hours. DESIGN: A prospective chart review was conducted in April 1995. Pharmacy billing data and infection control data were compared before and after policy implementation. SETTING: A 725-bed university teaching institution. PATIENTS: All patients receiving vancomycin during April 1995. MAIN OUTCOME MEASURES: Appropriateness of use was based on the Centers for Disease Control and Prevention (CDC) recommendations for prudent vancomycin use. RESULTS: A total of 333 courses of vancomycin therapy were reviewed. Vancomycin use was appropriate in 219 (66%) courses. Of the 114 courses that did not meet the CDC guidelines, 76 (67%) were for empiric use, 35 (31%) were for prophylactic use, and 3 (3%) were for therapeutic use. Overall, the total number of grams used decreased 9%, grams per 1000 patient-days decreased by 10, and the total number of patients exposed to vancomycin decreased 0.5%. Several services had large decreases in vancomycin use. Vancomycin expenditures decreased by $15788 for the 7-month time period. The incidence of VRE remained unchanged, at 30% of all enterococcal isolates 2 years after policy implementation. CONCLUSIONS: The limited restriction policy was effective in decreasing the total grams of vancomycin used. However, one-third of vancomycin therapy was inappropriate and the incidence of VRE was unchanged. A more stringent restriction policy could potentially increase appropriate use, further decrease the amount of vancomycin used, and decrease the incidence of VRE.     

HuR, a novel target of anti-Hu antibodies, is expressed in non-neural tissues

Paraneoplastic encephalomyelitis (PEM) is characterized by a diverse set of clinical signs that are limited to the nervous system. The serologic hallmark of PEM is the presence of circulating autoantibodies, collectively referred to as 'anti-Hu,' which immunoreact specifically with members of the Elav protein family. Until recently, the ELAV antigens were only detected in neurons, thus strongly supporting a role for anti-Hu antibodies in the selective neural tissue injury in PEM. The identification of HuR, however, a new member with a broad, non-neural pattern of RNA expression, raises several fundamental questions regarding PEM. First, why are non-neural tissues spared in PEM? Second, why is PEM predominantly associated with neuroendocrine tumors? To begin addressing these questions, we sought to determine whether the antibody response to HuR differs from the neural-specific counterparts in patients with PEM, and to characterize the protein expression pattern of this novel antigen in peripheral tissues and tumors. Using sera from 11 patients with Hu-positive PEM, we found that the majority of samples (73%) were weakly or non-reactive for recombinant HuR on Western blot, in contrast to consistently strong immunoreactivity with the neural-specific members HuD and Hel-N1. We also demonstrate that HuR is expressed at the protein level in both non-neural tissues and non-neuroendocrine tumors. These findings suggest that immunoreactive differences among Elav family members may contribute to the neural-restrictive pattern of tissue injury in patients with PEM.     

Donor leukocyte infusions for recurrent hematologic malignancies after allogeneic bone marrow transplantation: impact of infused and residual donor T cells

OBJECTIVE: To prospectively evaluate whether subcutaneous buffered lidocaine (SQBL) significantly reduces the pain or adversely affects the success rate of i.v. cannulation (IVC) in adult ED patients. METHODS: A convenience sample of patients > or=18 years old requiring IVC in a regional military ED were prospectively randomized to receive SQBL, SQ normal saline with 0.9% benzyl alcohol (SQNS), or no pretreatment (NPTx), prior to IVC with an 18-gauge angiocatheter. SQ infiltration was accomplished using a 27-gauge insulin syringe. Investigators and patients were blinded to SQBL and SQNS in the pretreatment groups. The number of attempts at IVC was recorded for each patient. A 100-mm visual analog pain scale (VAPS) was used to record pain scores for both SQ infiltration and IVC. Comparisons of the mean numbers of attempts to achieve IVC and of the VAPS scores were accomplished by analysis of variance followed by Duncan's multiple range test if significance was found. RESULTS: A total of 103 patients (SQBL-34, SQNS-30, and NPTx-39) were enrolled between November 15, 1996, and June 13, 1997. There were no significant differences among the groups in either the mean number of attempts (SQBL=1.35, 95% CI+/-0.260; SQNS=1.13, 95% CI +/-0.124; and NPTx=1.28, 95% CI+/-0.203) (p= 0.367) or the success rate on the first attempt (SQBL =79.4%, SQNS=86.7%, NPTx=79.5%) (p=0.533). The median VAPS score of IVC without pretreatment (21 mm, 95% CI+/-7.97) was greater than that for SQBL infiltration alone (10 mm, 95% CI+/-9.11), SQNS infiltration alone (9 mm, 95% CI+/-7.37), and IVC after SQBL (6 mm, 95% CI+/-9.18) (p < 0.009 for each group). SQNS infiltration had no significant effect on the VAPS score of subsequent IVC (20 mm, 95% CI+/-10.5) compared with IVC without pretreatment (21 mm). CONCLUSIONS: SQBL significantly reduced the pain, while not adversely affecting the success rate, of IVC in adult patients in the ED.     

Rabies prophylaxis following the feeding of a rabid pony

A survey was performed to identify people who were exposed to a rabid pony and determine whether or not they received rabies postexposure prophylaxis (PEP). Sixty-one visitors who came in contact with the rabid pony were identified. These visitors heard about the rabid pony via the news media. Forty-five visitors were exposed during the 2 weeks before the pony died. Thirty-two of these 45 visitors received PEP. Thirty-one visitors had or may have had saliva contact to an open wound or mucosa and all 31 received PEP. Fourteen visitors had no saliva contact to a wound or mucosa and one received PEP. Sixteen visitors were exposed before the pony was potentially shedding rabies virus and one received PEP. No visitor was bitten by the pony. Most of the persons 31/33 (94%) who received PEP had an exposure for which PEP was indicated. Nonbite transmission of rabies is discussed.     

The effectiveness of psychiatric treatment for HIV-infected patients

p-hydroxymethamphetamine (OHMAP) is one of the major metabolites of the widely abused drug methamphetamine (MAP). The demethylation of OHMAP to p-hydroxyamphetamine (OHAP) has been shown in vitro but has never been reported in vivo. The disposition kinetics as well as the metabolism of OHMAP was investigated employing a sensitive HPLC method which can separate the enantiomers of OHMAP and OHAP. Both conjugated and unconjugated forms of these compounds can be quantitated. Male Sprague-Dawley rats were given an iv bolus of racemic OHMAP (20 mg kg-1) and serum and urine samples were collected at selected times. The serum concentration-time data for OHMAP enantiomers could be described by a biexponential equation. The clearance of D-OHMAP (93.5 mL min-1 kg-1) was slightly, but statistically significantly, greater than that of the L-enantiomer (83.9 mL min-1 kg-1). The steady-state volumes of distribution of L- and D-OHMAP were (mean +/- SD) 3.15 +/- 0.84 and 4.23 +/- 1.76 L kg-1, respectively. No significant concentrations or amounts of OHAP enantiomers could be detected in any serum or urine sample. Rats excreted more unchanged L-OHMAP (34%) than D-OHMAP (29%). In contrast, more conjugated D-OHMAP (57%) was recovered compared to the conjugated L-OHMAP (52%). The results suggest that there is slight stereoselectivity in the disposition of OHMAP enantiomers. The N-demethylation product (OHAP) was not produced in vivo.     

Antibody to GBV-C second envelope glycoprotein (anti-GBV-C E2): is it a marker for immunity?

In previous research, the drug flumazenil has been categorized both as a pure benzodiazepine antagonist and as a benzodiazepine partial agonist. The following studies used an elevated plus maze to test whether flumazenil would exert any antianxiety action in rats. While chlordiazepoxide (3.0 mg/kg), ethanol (0.75 g/kg), and the atypical benzodiazepine zolpidem (1.0 mg/kg) all significantly increased time spent on the open arms and percent open arm entries, flumazenil (1-10 mg/kg) alone did not produce any anxiolytic effects on the maze. Withdrawal from chronic ethanol treatment led to a decrease in open arm time and percent open arm entries. Flumazenil (3.0 mg/kg) blocked these changes, suggesting that the effects of flumaxenil are at least partially dependent upon the levels of stress or anxiety in the subjects. An anxiolytic action of flumazenil was not seen following the central administration of the neuropeptide corticotropin-releasing factor (CRF), which reduced open arm time on the elevated plus maze. These results support the hypothesis that the mechanism of action for flumazenil effects on the anxiety observed during ethanol withdrawal involves antagonism of an endogenous benzodiazepine inverse agonist, rather than activity as a partial agonist or blockade of CRF-mediated effects.     

Inactivation of 3-hydroxy-3-methylglutaryl-CoA synthase and other Acyl-CoA-utilizing enzymes by 3-Oxobutylsulfoxyl-CoA

3-Oxobutylsulfoxyl-CoA has been produced by oxidation of S-3-oxobutyl-CoA, the thioether analog of acetoacetyl-CoA. Avian hydroxymethylglutaryl-CoA (HMG-CoA) synthase is inactivated by oxobutylsulfoxyl-CoA in a time-dependent fashion. Protection against inactivation is afforded by the substrate, acetyl-CoA, suggesting that inactivation involves modification of the enzyme's active site. Pretreatment of HMG-CoA synthase with the inactivator blocks the enzyme's ability to form Michaelis and acetyl-S-enzyme intermediates, supporting the hypothesis that modification is active-site directed. Incubation of enzyme with oxobutylsulfoxyl-[32P]CoA followed by precipitation with trichloroacetic acid indicates that inactivation correlates with stoichiometric formation of a covalent adduct between enzyme and a portion of the inactivator that includes the CoA nucleotide. The observation of reagent partitioning suggests that HMG-CoA synthase catalyzes conversion of oxobutylsulfoxyl-CoA into a reactive species that modifies the protein. Treatment of inactivated enzyme with DTT or other mercaptans restores enzyme activity and reverses the covalent modification with release of CoASH. Oxobutylsulfoxyl-CoA inactivates beta-ketothiolase and HMG-CoA lyase in a process that is also reversed by DTT. These three enzymes all contain active site cysteines, suggesting that inactivation results from disulfide formation between a cysteine and the CoA moiety of the inhibitor. The data are consistent with the hypothesis that enzymatic cleavage of oxobutylsulfoxyl-CoA results in the transient formation of a sulfenic acid derivative of CoA which subsequently reacts to form a stable disulfide linkage to protein.     

Telemedicine and fetal ultrasonography: assessment of technical performance and clinical feasibility

OBJECTIVE: Our aim was to determine the performance and clinical feasibility of telesonography for the interpretation of fetal anatomic scans sent from a remote location compared with those obtained at a tertiary care prenatal ultrasonography center. STUDY DESIGN: Routine ultrasonographic studies from 35 patients were remotely interpreted. Evaluation included a blinded comparison of the sonographer's assessment of 38 fetal structures with that of the physician at the tertiary care center. Technical evaluation included system reliability and the number of digital telephone lines required for adequate real-time visualization. RESULTS: The mean gestational age at the time of the ultrasonography was 25.84 +/- 6.8 weeks (range 14 to 38). There was complete consistency of interpretation for 25 of 38 (66%) fetal structures. Thirteen structures had discrepancies in visualization, reflecting a difference in the adequacy of visualization, not the normalcy or identity of the structures. Three digital (integrated switching digital network, ISDN) telephone lines were required for real-time visualization. CONCLUSION: Our preliminary experience supports telesonography as a clinically useful tool for remote interpretation of fetal ultrasonographic examinations. Further studies are warranted for the continued evaluation of this emerging technology.     

Inflationary tendencies in judging the yield of depression research

The mood around mood disorders is one of optimism. Progress in diagnosis and treatment is generally felt to be considerable. Zeitgeist rests on convictions. In this case the main supporting convictions are the following: depression is a very frequent disorder and its diagnosis has improved greatly; we dispose of more or less specific agents to control depression: biological psychiatric research made great strides, particularly in the field of affective disorders; new antidepressants are properly tested before being clinically introduced. Each of these convictions is critically analysed. It is concluded that each of these claims is either a half-truth or not true. Apparently reality awareness and reality testing are out of balance. This harms the prospects of research, particularly biological research. Ways to avoid the stalemate are discussed.     

Whole blood cytokine assays--a new generation of diagnostic tests for tuberculosis?

We describe a patient with Sj?gren's syndrome who died from undiagnosed adrenocortical failure. A positive test for adrenocortical antibody, performed pre-terminally, suggested the underlying diagnosis, which was subsequently confirmed at post-mortem. This case highlights the rare association of Sj?gren's syndrome with occult adrenocortical failure. Perhaps a greater awareness of this association and more frequent serological screening are necessary to prevent a fatal outcome.