Effect of screening, brief intervention and referral to treatment for unhealthy alcohol and other drug use in mental health treatment settings: a randomized controlled trial.

AIMS: To test the efficacy of a brief intervention to reduce alcohol or drug use and to promote use of addiction services among patients seeking mental health treatment. DESIGN AND SETTING: A multi-centre, longitudinal, two-group randomized controlled trial with randomization within each of two mental health treatment systems located in Ventura County and Los Angeles County in California, USA. PARTICIPANTS: A total of 718 patients (49.2% female) aged 18 and older with a mental health diagnosis and either a heavy drinking day or any use of cannabis or stimulants in the past 90 days. INTERVENTION AND COMPARATOR: A motivation-based brief intervention with personalized feedback (screening, brief intervention and referral to treatment (SBIRT) condition) (n = 354) or a health education session (control condition) (n = 364). MEASUREMENTS: Primary outcomes included frequency of heavy drinking days, days of cannabis use and days of stimulant use at the primary end-point 3 months post-baseline. Secondary outcomes included frequency and abstinence from substance use out to a 12-month follow-up and the use of addiction treatment services. FINDINGS: Participants in the SBIRT condition had fewer heavy drinking days [odds ratio (OR) = 0.53; 95% credible interval (CrI) = 0.48-0.6] and fewer days of stimulant use (OR = 0.58; 95% CrI = 0.50-0.66) at the 3-month follow-up compared with participants in the health education condition. Participants in the SBIRT condition did not comparatively reduce days of cannabis use at the 3-month follow-up (OR = 0.93; 95% CrI = 0.85-1.01). Secondary outcomes indicated sustained effects of SBIRT on reducing the frequency of heavy drinking days and days of stimulant use. No effects were observed on abstinence rates or use of addiction treatment services. CONCLUSIONS: Screening and brief intervention for unhealthy alcohol and drug use in mental health treatment settings were effective at reducing the frequency of heavy drinking and stimulant use.

Truncated beta-amyloid peptide channels provide an alternative mechanism for Alzheimer's Disease and Down syndrome.

Full-length amyloid beta peptides (Abeta(1-40/42)) form neuritic amyloid plaques in Alzheimer's disease (AD) patients and are implicated in AD pathology. However, recent transgenic animal models cast doubt on their direct role in AD pathology. Nonamyloidogenic truncated amyloid-beta fragments (Abeta(11-42) and Abeta(17-42)) are also found in amyloid plaques of AD and in the preamyloid lesions of Down syndrome, a model system for early-onset AD study. Very little is known about the structure and activity of these smaller peptides, although they could be the primary AD and Down syndrome pathological agents. Using complementary techniques of molecular dynamics simulations, atomic force microscopy, channel conductance measurements, calcium imaging, neuritic degeneration, and cell death assays, we show that nonamyloidogenic Abeta(9-42) and Abeta(17-42) peptides form ion channels with loosely attached subunits and elicit single-channel conductances. The subunits appear mobile, suggesting insertion of small oligomers, followed by dynamic channel assembly and dissociation. These channels allow calcium uptake in amyloid precursor protein-deficient cells. The channel mediated calcium uptake induces neurite degeneration in human cortical neurons. Channel conductance, calcium uptake, and neurite degeneration are selectively inhibited by zinc, a blocker of amyloid ion channel activity. Thus, truncated Abeta fragments could account for undefined roles played by full length Abetas and provide a unique mechanism of AD and Down syndrome pathologies. The toxicity of nonamyloidogenic peptides via an ion channel mechanism necessitates a reevaluation of the current therapeutic approaches targeting the nonamyloidogenic pathway as avenue for AD treatment.