Anti-implantation agents: Part I. 1-Arylthiosemicarbazides

Several 1-arylthiosemicarbazides, 2-arylhydrazinothiazolines and 2-arylhydrazinodihydrothiazines have been examined for their antiimplantation activity in rats. Among the active compounds, 4-methyl-1-(3,5-bistrifluorornethylphenyl)thioserni-carbazide (3, C 2696-Go) and the corresponding 4,4-dimethyl (47), ethyl (4), n-butyl (5) and allyl (6) derivatives completely inhibit implantation at doses of 10, 3, 20, 20 and 30mg/kg respectively. The 3,4-dichlorophenyl analogue (32) is effective at a dose of 30mg/kg. 2-(3,5-Bistrifluoromethylphenyl)hydrazinothiazoline (51) and the corresponding dlhydrothiazine (63) show a weaker activity. The biological profile of C 2696-Go has been investigated in detail. It appears to prevent implantation by its antiuterotropic activity and ability to inhibit desiduoma formation

The Hawthorne Effect: a randomised, controlled trial

Background: The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow- up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia.Methods: Participants in a dementia trial were randomised to intensive follow- up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD).Results: We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co- variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95% Cl -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant- rated quality of life score (n = 142; mean difference = -1.382; 95% Cl -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life.Conclusion: We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning

Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil

<p>Abstract</p> <p>Background</p> <p>The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment.</p> <p>Method</p> <p>AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study).</p> <p>Results</p> <p>Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain.</p> <p>Conclusion</p> <p>The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease.</p