The in vitro activity of LY 146032, a cyclic lipopeptide antibiotic belonging to the class of agents designated A21978C, was compared with those of vancomycin, cefpirome, cefotaxime, and clindamycin against selected gram-positive bacteria. The new drug inhibited all staphylococcal isolates, including methicillin-resistant strains, at concentrations of less than or equal to 1.0 microgram/ml. The activity of LY 146032 was comparable to that of vancomycin against most streptococci, but the latter demonstrated greater potency against Streptococcus faecium and penicillin-resistant strains of pneumococci and viridans group streptococci. LY 146032 was markedly less active than vancomycin against Listeria monocytogenes (MICs for 90% of strains tested, 16 and 1.0 microgram/ml, respectively). The activity of LY 146032 was enhanced as the concentration of calcium in the test medium was increased. MBCs were within eightfold of the MIC for each of 12 strains tested. In a rat model of enterococcal endocarditis, the administration of LY 146032 resulted in increased survival and a reduction in the bacterial titer within cardiac vegetations compared with untreated control animals.
ObjectivesTo determine whether humour therapy reduces depression (primary outcome), agitation and behavioural disturbances and improves social engagement and quality-of-life in nursing home residents.DesignThe Sydney Multisite Intervention of LaughterBosses and ElderClowns study was a single-blind cluster randomised controlled trial of humour therapy.Setting35 Sydney nursing homes.ParticipantsAll eligible residents within geographically defined areas within each nursing home were invited to participate.InterventionProfessional ‘ElderClowns’ provided 9–12 weekly humour therapy sessions, augmented by resident engagement by trained staff ‘LaughterBosses’. Controls received usual care.MeasurementsDepression scores on the Cornell Scale for Depression in Dementia, agitation scores on the Cohen-Mansfield Agitation Inventory, behavioural disturbance scores on the Neuropsychiatric Inventory, social engagement scores on the withdrawal subscale of Multidimensional Observation Scale for Elderly Subjects, and self-rated and proxy-rated quality-of-life scores on a health-related quality-of-life tool for dementia, the DEMQOL. All outcomes were measured at the participant level by researchers blind to group assignment.RandomisationSites were stratified by size and level of care then assigned to group using a random number generator.ResultsSeventeen nursing homes (189 residents) received the intervention and 18 homes (209 residents) received usual care. Groups did not differ significantly over time on the primary outcome of depression, or on behavioural disturbances other than agitation, social engagement and quality of life. The secondary outcome of agitation was significantly reduced in the intervention group compared with controls over 26 weeks (time by group interaction adjusted for covariates: p=0.011). The mean difference in change from baseline to 26 weeks in Blom-transformed agitation scores after adjustment for covariates was 0.17 (95% CI 0.004 to 0.34, p=0.045).ConclusionsHumour therapy did not significantly reduce depression but significantly reduced agitation.Trial registrationAustralian New Zealand Clinical Trials Registry -ACTRN12611000462987.
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