Influence of covariates on heterogeneity in Hamilton Anxiety Scale ratings in placebo-controlled trials of benzodiazepines in generalized anxiety disorder: Systematic review and meta-analysis.

BACKGROUND: Generalized anxiety disorder is a common psychiatric condition that is associated with decreased quality of life and significant disability. Benzodiazepines are anti-anxiety drugs used widely in the treatment of generalized anxiety disorder. This study examines the influence of several variables on benzodiazepine efficacy in generalized anxiety disorder. METHOD: We performed a systematic review of placebo-controlled randomized controlled trials with benzodiazepines in generalized anxiety disorder. Fifty-eight studies were deemed eligible to include in the meta-analysis. The studies dated from 1977 to 2013 and included over 5400 participants. From each paper, we extracted: benzodiazepine name and dose, dosing regimen, baseline Hamilton Anxiety Scale (HAM-A) score, change in HAM-A score at study endpoint, drop-out rate, year of study publication, diagnostic criteria used, study size, study duration, location, any conflicts of interest and side-effect profile. We then assessed the influence, direct and indirect, of individual variables on the primary outcome (mean difference at endpoint, HAM-A score). RESULTS: Three factors were shown to be associated statistically with change in HAM-A; baseline HAM-A for benzodiazepine arm, baseline HAM-A for the placebo arm, and duration of the study. A higher baseline HAM-A in both arms was associated with a greater mean difference in HAM-A. A shorter study length was also associated with a greater mean difference. DISCUSSION: The major factors determining benzodiazepine response was baseline anxiety level for the benzodiazepine arm and study duration. In any design of further meta-analyses and clinical trials for generalized anxiety disorder we suggest that these should be considered these as confounding factors.

Consent, competence and lies to children: veracity in paediatric care.

Principles of consent and autonomy based on adult-oriented bioethics must be modified to take account of the cognitive development occurring in childhood. That development differentially affects executive and more theoretical intelligence and is greatly influenced by experience. Thus, a judgment about a matter of degree is required by clinicians dealing with children, particularly when children diverge from the choices that would be endorsed by the adults and clinicians surrounding them. If we accept that partnership and the evolution of consent away from a formal procedure are both indicative of current ethical and medico-legal thinking, then it follows that the involvement of a child in an open-ended conversation taking account of the realistic prospects and the subjective experiences associated with treatment is the right way to proceed and that it should reflect the ability of the child to understand what is at stake and how it will affect her or him. That carries implications for the child's access to adequate information about the condition, the treatment, and the decisions being made.