Improving outpatient treatment in schizophrenia: effects of computerized guideline implementation--results of a multicenter-study within the German research network on schizophrenia.

Schizophrenia clinical practice guidelines are developed to provide expert- and evidence-based advice to practicing psychiatrists in order to improve the management of this disorder. However, the application of these guidelines in everyday health care can still be described as nonsatisfying. Within the project "Guideline-supported quality management in outpatient treatment", we investigated whether guideline adherence and quality of outcome can be improved by implementing a computer-based, guideline-oriented decision-support system. Therefore, a disease-specific decision-support system was developed interactively presenting guidelines to support the physicians decision-making process during the treatment of schizophrenia patients. We evaluated the system in a control group design: An experimental group consisting of 15 psychiatrists in private practice used the decision-support system, thus documenting the treatment of schizophrenic patients. Guideline-based algorithms were interactively and case specifically displayed on the PC-screen as soon as predefined triggers were met. A first control group in Munich provided treatment-as-usual, documenting the treatment via paper-pencil. Two further physician groups served as additional comparison groups: one also documented electronically using the decision-support system, however without receiving electronic guideline support, the second group carried out traditional quality circles while also using the paper-pencil approach. As a result of the intervention, we observed a strong initial but time-limited improvement with respect to the core aspects of outpatient treatment in schizophrenia in the experimental group. The findings suggest that decision-support systems, despite their limitations, can be used to enhance treatment outcome in schizophrenia outpatient care.

Novel non-nucleoside inhibitors of cytomegaloviruses (BAY 38-4766): in vitro and in vivo antiviral activity and mechanism of action.

For two decades it has been impossible to develop drugs with novel mechanisms of action against herpesviruses, and treatment has been confined largely to the use of inhibitors of viral DNA polymerase. As a representative of a novel inhibitory approach, the non-nucleosidic BAY 38-4766 was identified as a highly selective inhibitor of human cytomegalovirus (HCMV). The compound selectively inhibits not only HCMV strains, including ganciclovir-resistant, ganciclovir/foscarnet and ganciclovir/cidofovir double-resistant clinical isolates, but also a number of monkey and rodent cytomegaloviruses. In a murine cytomegalovirus (MCMV) pathogenicity model in mice, antiviral efficacy and excellent tolerability were demonstrated. BAY 38-4766-resistant HCMV and MCMV strains are not cross-resistant to the nucleoside analogues ganciclovir and cidofovir or the pyrophosphate analogue foscarnet, indicating a different mode of action. Mechanistic studies demonstrated that the high selectivity of this drug class is most likely due to the inhibition of a late stage of the viral replication cycle. Sequence analyses of resistant HCMV and MCMV strains revealed mutations in UL89 and UL104, proteins known to be involved in viral DNA cleavage and packaging. Consequently, the drug is highly specific for the viral as opposed to cellular functions, since UL89 is related to a bacteriophage terminase and no human equivalent exists. In addition, because some of the genes of the viral DNA cleavage and packaging complex are highly conserved among herpesviruses, development of broad-spectrum agents covering additional human herpesviruses might be possible using this approach.

Inhibition of murine cytomegalovirus and human cytomegalovirus by a novel non-nucleosidic compound in vivo.

Novel non-nucleosidic compounds have recently been identified as potent inhibitors of the human cytomegalovirus (HCMV) and murine cytomegalovirus (MCMV) in vitro. We have now investigated the antiviral activity of these compounds in MCMV-infected NOD/LtSz-scid/j mice that lack functional T, B and, in contrast to C.B-17/Icr scid/scid mice, natural killer cells, and represent a novel model for cytomegalovirus infection in immunocompromised hosts. BAY 38-4766 (3-hydroxy-2,2-dimethyl-N-[4(([5-(dimethylamino)-1-naphthyl]sulfonyl)amino)- phenyl]propanamide) was identified as the most potent representative of this class of antiviral compounds. Per os administration of BAY 38-4766 at dosages > or = 10 mg/kg body weight led to antiviral effects that were comparable to ganciclovir 9-(1,3-dihydroxy-2-propoxymethyl)-guanine (Cymevene) as measured by survival and levels of viral DNA in organs of infected mice. In order to assess the anti-HCMV activity of BAY 38-4766 in vivo, we used a model, in which HCMV-infected human cells were entrapped in hollow fibers and subsequently transplanted into immunodeficient mice. Using this model, we demonstrated antiviral activity of BAY 38-4766 similar to that of ganciclovir. We conclude that BAY 38-4766 shows potential as an anti-HCMV drug.