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Additional file 1: Stata command routines. Table: GENDEP baseline demographic and clinical characteristics.

ObjectiveStudies have shown that antidepressants are no better than placebo in treating depression in dementia. The authors examined antidepressant efficacy in subgroups of depression in dementia with different depressive symptom profiles.MethodsThis study focuses on exploratory secondary analyses on the randomized, parallel-group, double-blind, placebo-controlled Health Technology Assessment Study of the Use of Antidepressants for Depression in Dementia (HTA-SADD) trial. The setting included old-age psychiatry services in nine centers in England. The participants included 326 patients meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association probable/possible Alzheimer disease criteria, and Cornell Scale for Depression in Dementia (CSDD) scores of 8 or more. Intervention was placebo (n = 111), sertraline (n = 107), or mirtazapine (n = 108). Latent class analyses (LCA) on baseline CSDD items clustered participants into symptom-based subgroups. Mixed-model analysis evaluated CSDD improvement at 13 and 39 weeks by randomization in each subgroup.ResultsLCA yielded 4 subgroups: severe (n = 34), psychological (n = 86), affective (n = 129), and somatic (n = 77). Mirtazapine, but not sertraline, outperformed placebo in the psychological subgroup at week 13 (adjusted estimate: –2.77 [standard error (SE) 1.16; 95% confidence interval: –5.09 to –0.46]), which remained, but lost statistical significance at week 39 (adjusted estimate: –2.97 [SE 1.59; 95% confidence interval: –6.15 to 0.20]). Neither sertraline nor mirtazapine outperformed placebo in the other subgroups.ConclusionBecause of the exploratory nature of the analyses and the small sample sizes for subgroup analysis there is the need for caution in interpreting these data. Replication of the potential effects of mirtazapine in the subgroup of those with depression in dementia with “psychological” symptoms would be valuable. These data should not change clinical practice, but future trials should consider stratifying types of depression in dementia in secondary analyses.

CONSORT 2010 checklist. (DOCX 209 kb)

Unadjusted mean EDE and ZAN score by treatment group for all post randomisation time points and baseline (time 0). Lowest score if best. Error bars show 95Â % CI. EDE Eating Disorder Examination, ZAN Zanarini Rating Scale. (DOCX 74 kb)

Aims: To determine whether the provision of contingency management using financial incentives to improve hepatitis B vaccine completion in people who inject drugs entering community treatment represents a cost-effective use of health-care resources. Design: A probabilistic cost-effectiveness analysis was conducted, using a decision-tree to estimate the short-term clinical and health-care cost impact of the vaccination strategies, followed by a Markov process to evaluate the long-term clinical consequences and costs associated with hepatitis B infection. Settings and participants: Data on attendance to vaccination from a UK cluster randomized trial. Intervention: Two contingency management options were examined in the trial: fixed versus escalating schedule financial incentives. Measurement: Life-time health-care costs and quality-adjusted life years discounted at 3.5% annually; incremental cost-effectiveness ratios. Findings: The resulting estimate for the incremental life-time health-care cost of the contingency management strategy versus usual care was £21.86 [95% confidence interval (CI) = -£12.20 to 39.86] per person offered the incentive. For 1000 people offered the incentive, the incremental reduction in numbers of hepatitis B infections avoided over their lifetime was estimated at 19 (95% CI = 8-30). The probabilistic incremental cost per quality adjusted life-year gained of the contingency management programme was estimated to be £6738 (95% CI = £6297-7172), with an 89% probability of being considered cost-effective at a threshold of £20000 per quality-adjusted life years gained (97.60% at £30000). Conclusions: Using financial incentives to increase hepatitis B vaccination completion in people who inject drugs could be a cost-effective use of health-care resources in the UK as long as the incidence remains above 1.2%.

We report the syntheses and activities of a wide range of thiazolides [viz., 2-hydroxyaroyl-N-(thiazol-2-yl)amides] against hepatitis B virus replication, with QSAR analysis of our results. The prototypical thiazolide, nitazoxanide [2-hydroxybenzoyl-N-(5-nitrothiazol-2-yl)amide, NTZ] 1 is a broad spectrum antiinfective agent effective against anaerobic bacteria, viruses, and parasites. By contrast, 2-hydroxybenzoyl-N-(5-chlorothiazol-2-yl)amide 3 is a novel, potent, and selective inhibitor of hepatitis B replication (EC(50) = 0.33 μm) but is inactive against anaerobes. Several 4'- and 5'-substituted thiazolides show good activity against HBV; by contrast, some related salicyloylanilides show a narrower spectrum of activity. The ADME properties of 3 are similar to 1; viz., the O-acetate is an effective prodrug, and the O-aryl glucuronide is a major metabolite. The QSAR study shows a good correlation of observed EC(90) for intracellular virions with thiazolide structural parameters. Finally we discuss the mechanism of action of thiazolides in relation to the present results.