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Systems analysis of adverse drug events. ADE Prevention Study Group.: JAMA, Vol. 274, No. 1. (5 July 1995), pp. 35-43.OBJECTIV E--To identify and evaluate the systems failures that underlie errors causing adverse drug events (ADEs) and potential ADEs. DESIGN--System s analysis of events from a prospective cohort study. PARTICIPANTS-- All admissions to 11 medical and surgical units in two tertiary care hospitals over a 6-month period. MAIN OUTCOME MEASURES--Erro rs, proximal causes, and systems failures. METHODS--Error s were detected by interviews of those involved. Errors were classified according to proximal cause and underlying systems failure by multidisciplin ary teams of physicians, nurses, pharmacists, and systems analysts. RESULTS--Durin g this period, 334 errors were detected as the causes of 264 preventable ADEs and potential ADEs. Sixteen major systems failures were identified as the underlying causes of the errors. The most common systems failure was in the dissemination of drug knowledge, particularly to physicians, accounting for 29% of the 334 errors. Inadequate availability of patient information, such as the results of laboratory tests, was associated with 18% of errors. Seven systems failures accounted for 78% of the errors; all could be improved by better information systems. CONCLUSIONS--H ospital personnel willingly participated in the detection and investigation of drug use errors and were able to identify underlying systems failures. The most common defects were in systems to disseminate knowledge about drugs and to make drug and patient information readily accessible at the time it is needed. Systems changes to improve dissemination and display of drug and patient data should make errors in the use of drugs less likely.LL Leape, DW Bates, DJ Cullen, J Cooper, HJ Demonaco, T Gallivan, R Hallisey, J Ives, N Laird, G Laffel

Source: JAMA, Vol. 274, No. 1. (5 July 1995), pp. 35-43.
Incidence of adverse drug events and potential adverse drug events. Implications for prevention. ADE Prevention Study Group.: JAMA, Vol. 274, No. 1. (5 July 1995), pp. 29-34.OBJECTIV ES--To assess incidence and preventability of adverse drug events (ADEs) and potential ADEs. To analyze preventable events to develop prevention strategies. DESIGN--Prospe ctive cohort study. PARTICIPANTS-- All 4031 adult admissions to a stratified random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical intensive care units and four medical and two surgical general care units. MAIN OUTCOME MEASURES--Adve rse drug events and potential ADEs. METHODS--Incid ents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented ADEs or potential ADEs and as to severity and preventability . RESULTS--Over 6 months, 247 ADEs and 194 potential ADEs were identified. Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions, for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs. Of all ADEs, 1% were fatal (none preventable), 12% life-threateni ng, 30% serious, and 57% significant. Twenty-eight percent were judged preventable. Of the life-threateni ng and serious ADEs, 42% were preventable, compared with 18% of significant ADEs. Errors resulting in preventable ADEs occurred most often at the stages of ordering (56%) and administration (34%); transcription (6%) and dispensing errors (4%) were less common. Errors were much more likely to be intercepted if the error occurred earlier in the process: 48% at the ordering stage vs 0% at the administration stage. CONCLUSION--Ad verse drug events were common and often preventable; serious ADEs were more likely to be preventable. Most resulted from errors at the ordering stage, but many also occurred at the administration stage. Prevention strategies should target both stages of the drug delivery process.DW Bates, DJ Cullen, N Laird, LA Petersen, SD Small, D Servi, G Laffel, BJ Sweitzer, BF Shea, R Hallisey

Source: JAMA, Vol. 274, No. 1. (5 July 1995), pp. 29-34.
Intermediate Jacobians and ADE Hitchin Systems: (21 Jul 2006)Let $?$ be a smooth projective complex curve and $\mathfrakg$ a simple Lie algebra of type $ ADE$ with associated adjoint group $G$. For a fixed pair $(?, \mathfrakg)$, we construct a family of quasi-projecti ve Calabi-Yau threefolds parameterized by the base of the Hitchin integrable system associated to $(?,\mathfrakg )$. Our main result establishes an isomorphism between the Calabi-Yau integrable system, whose fibers are the intermediate Jacobians of this family of Calabi-Yau threefolds, and the Hitchin system for $G$, whose fibers are Prym varieties of the corresponding spectral covers. This construction provides a geometric framework for Dijkgraaf-Vafa transitions of type $ ADE$. In particular, it predicts an interesting connection between adjoint $ ADE$ Hitchin systems and quantization of holomorphic branes on Calabi-Yau manifolds.Duil iu-Emanuel Diaconescu, Ron Donagi, Tony Pantev

Source: (21 Jul 2006)
Consensus List of Signals to Detect Potential Adverse Drug Reactions in Nursing Homes: Journal of the American Geriatrics Society, Vol. 56, No. 5. (May 2008), pp. 808-815.Handle r, M Steven, Hanlon, T Joseph, Perera, Subashan, Roumani, F Yazan, Nace, A David, Fridsma, B Douglas, Saul, I Melissa, Castle, G Nicholas, Studenski, A Stephanie

Source: Journal of the American Geriatrics Society, Vol. 56, No. 5. (May 2008), pp. 808-815.
Instabilities in multiserotype disease models with antibody-depen dent enhancement: Journal of Theoretical Biology, Vol. In Press, Accepted ManuscriptLora Billings, Ira Schwartz, Leah Shaw, Marie Mccrary, Donald Burke, Derek Cummings

Source: Journal of Theoretical Biology, Vol. In Press, Accepted Manuscript
Monoclonal antibody-media ted enhancement of dengue virus infection in vitro and in vivo and strategies for prevention: Proceedings of the National Academy of Sciences, Vol. 104, No. 22. (29 May 2007), pp. 9422-9427.Infe ction with dengue virus (DENV) or any other flavivirus induces cross-reactive , but weakly neutralizing or nonneutralizin g, antibodies that recognize epitopes involving the fusion peptide in the envelope glycoprotein. Humanized mAb IgG 1A5, derived from a chimpanzee, shares properties of cross-reactive antibodies. mAb IgG 1A5 up-regulated DENV infection by a mechanism of antibody-depen dent enhancement (ADE) in a variety of Fc receptor-beari ng cells in vitro. A 10- to 1,000-fold increase of viral yield in K562 cells, dependent on the DENV serotype, was observed over a range of subneutralizin g concentrations of IgG 1A5. A significant increase of DENV-4 viremia titers (up to 100-fold) was also demonstrated in juvenile rhesus monkeys immunized with passively transferred dilutions of IgG 1A5. These results, together with earlier findings of ADE of DENV-2 infection by a polyclonal serum, establish the primate model for analysis of ADE. Considering the abundance of these cross-reactive antibodies, our observations confirm that significant viral amplification could occur during DENV infections in humans with prior infection or with maternally transferred immunity, possibly leading to severe dengue. Strategies to eliminate ADE were explored by altering the antibody Fc structures responsible for binding to Fc receptors. IgG 1A5 variants, containing amino acid substitutions from the Fc region of IgG2 or IgG4 antibodies, reduced but did not eliminate DENV-4-enhanci ng activity in K562 cells. Importantly, a 9-aa deletion at the N terminus of the CH2 domain in the Fc region abrogated the enhancing activity. 10.1073/pnas.0 703498104Ana Goncalvez, Ronald Engle, Marisa St. Claire, Robert Purcell, Ching-Juh Lai

Source: Proceedings of the National Academy of Sciences, Vol. 104, No. 22. (29 May 2007), pp. 9422-9427.
Complement protein C1q inhibits antibody-depen dent enhancement of flavivirus infection in an IgG subclass-speci fic manner.: Cell host & microbe, Vol. 2, No. 6. (13 December 2007), pp. 417-426.Severe dengue virus infection can occur in humans with pre-existing antibodies against the virus. This observation led to the hypothesis that a subneutralizin g antibody level in vivo can increase viral burden and cause more severe disease. Indeed, antibody-depen dent enhancement of infection (ADE) in vitro has been described for multiple viruses, including the flaviviruses dengue virus and West Nile virus. Here, we demonstrate that the complement component C1q restricts ADE by anti-flaviviru s IgG antibodies in an IgG subclass-speci fic manner in cell culture and in mice. IgG subclasses that avidly bind C1q induced minimal ADE in the presence of C1q. These findings add a layer of complexity for the analysis of humoral immunity and flavivirus infection.E Mehlhop, C Ansarah-Sobrin ho, S Johnson, M Engle, DH Fremont, TC Pierson, MS Diamond

Source: Cell host & microbe, Vol. 2, No. 6. (13 December 2007), pp. 417-426.
Approximate Dimension Equalization in Vector-based Information Retrieval: (2000), pp. 423-430.Fan Jiang, Michael Littman

Source: (2000), pp. 423-430.
Adverse drug events associated with hospital admission.: The Annals of pharmacotherap y, Vol. 37, No. 1. (January 2003), pp. 5-11.OBJECTIVE : To increase the knowledge base on the frequency, causality, and avoidability of adverse drug events (ADEs) as a cause for admission in internal medicine or when occurring during hospitalizatio n. METHODS: A prospective study was performed for 6 periods of 8 days each. Epidemiologic data (e.g., age, gender, medical history), drug utilization, and adverse drug reactions on patients hospitalized during these periods were collected by a pharmacy student. RESULTS: A total of 156 patients (70 men and 86 women) were included in the study. The patients' mean age +/- SD was 66.5 +/- 18.1 years and mean length of stay was 13.2 +/- 9 days. Renal and hepatic insufficiency and previous history of drug intolerance were observed in 17.9%, 10.2%, and 2% of the hospitalized patients, respectively. Thirty-eight ADEs occurred in 32 patients; in 15 cases, ADEs were identified as the reason for admission, 10 cases occurred during hospitalizatio n, and 13 cases were present at admission, but were not the cause of admission. The most frequent ADEs involved the neurologic (23.6%), renal (15.7%), and hematologic (13.1%) systems. Among these 38 ADEs, 22 were considered avoidable (57.9%); 20 of these were associated with therapeutic errors (inappropriate administration , drug-drug interactions, dosage error, drug not stopped despite the onset of ADEs). Patients with ADEs stayed longer in the hospital and took more drugs both before and during their hospital stay (p < 0.05). CONCLUSIONS: Most of the ADEs observed in this study were avoidable. The risk/benefit ratio of administered drugs could be improved with better knowledge of the patients' medical history and the risk factors of ADEs.H Peyriere, S Cassan, E Floutard, S Riviere, JP Blayac, D Hillaire-Buys, A Le Quellec, S Hansel

Source: The Annals of pharmacotherapy, Vol. 37, No. 1. (January 2003), pp. 5-11.

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