AESOPS: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of opportunistic screening and stepped care interventions for older hazardous alcohol users in primary care.

BACKGROUND: There is clear evidence of the detrimental impact of hazardous alcohol consumption on the physical and mental health of the population. Estimates suggest that hazardous alcohol consumption annually accounts for 150,000 hospital admissions and between 15,000 and 22,000 deaths in the UK. In the older population, hazardous alcohol consumption is associated with a wide range of physical, psychological and social problems. There is evidence of an association between increased alcohol consumption and increased risk of coronary heart disease, hypertension and haemorrhagic and ischaemic stroke, increased rates of alcohol-related liver disease and increased risk of a range of cancers. Alcohol is identified as one of the three main risk factors for falls. Excessive alcohol consumption in older age can also contribute to the onset of dementia and other age-related cognitive deficits and is implicated in one-third of all suicides in the older population. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of a stepped care intervention against a minimal intervention in the treatment of older hazardous alcohol users in primary care. DESIGN: A multicentre, pragmatic, two-armed randomised controlled trial with an economic evaluation. SETTING: General practices in primary care in England and Scotland between April 2008 and October 2010. PARTICIPANTS: Adults aged ≥ 55 years scoring ≥ 8 on the Alcohol Use Disorders Identification Test (10-item) (AUDIT) were eligible. In total, 529 patients were randomised in the study. INTERVENTIONS: The minimal intervention group received a 5-minute brief advice intervention with the practice or research nurse involving feedback of the screening results and discussion regarding the health consequences of continued hazardous alcohol consumption. Those in the stepped care arm initially received a 20-minute session of behavioural change counselling, with referral to step 2 (motivational enhancement therapy) and step 3 (local specialist alcohol services) if indicated. Sessions were recorded and rated to ensure treatment fidelity. MAIN OUTCOME MEASURES: The primary outcome was average drinks per day (ADD) derived from extended AUDIT--Consumption (3-item) (AUDIT-C) at 12 months. Secondary outcomes were AUDIT-C score at 6 and 12 months; alcohol-related problems assessed using the Drinking Problems Index (DPI) at 6 and 12 months; health-related quality of life assessed using the Short Form Questionnaire-12 items (SF-12) at 6 and 12 months; ADD at 6 months; quality-adjusted life-years (QALYs) (for cost-utility analysis derived from European Quality of Life-5 Dimensions); and health and social care resource use associated with the two groups. RESULTS: Both groups reduced alcohol consumption between baseline and 12 months. The difference between groups in log-transformed ADD at 12 months was very small, at 0.025 [95% confidence interval (CI)--0.060 to 0.119], and not statistically significant. At month 6 the stepped care group had a lower ADD, but again the difference was not statistically significant. At months 6 and 12, the stepped care group had a lower DPI score, but this difference was not statistically significant at the 5% level. The stepped care group had a lower SF-12 mental component score and lower physical component score at month 6 and month 12, but these differences were not statistically significant at the 5% level. The overall average cost per patient, taking into account health and social care resource use, was £488 [standard deviation (SD) £826] in the stepped care group and £482 (SD £826) in the minimal intervention group at month 6. The mean QALY gains were slightly greater in the stepped care group than in the minimal intervention group, with a mean difference of 0.0058 (95% CI -0.0018 to 0.0133), generating an incremental cost-effectiveness ratio (ICER) of £1100 per QALY gained. At month 12, participants in the stepped care group incurred fewer costs, with a mean difference of -£194 (95% CI -£585 to £198), and had gained 0.0117 more QALYs (95% CI -0.0084 to 0.0318) than the control group. Therefore, from an economic perspective the minimal intervention was dominated by stepped care but, as would be expected given the effectiveness results, the difference was small and not statistically significant. CONCLUSIONS: Stepped care does not confer an advantage over minimal intervention in terms of reduction in alcohol consumption at 12 months post intervention when compared with a 5-minute brief (minimal) intervention. TRIAL REGISTRATION: This trial is registered as ISRCTN52557360. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 25. See the HTA programme website for further project information.

Electrophysiology of Ascaris muscle and anti-nematodal drug action.

Three groups of anthelmintic drugs act directly and selectively on muscle membrane receptors of parasitic nematodes. These groups of anthelmintics are: (1) The Nicotinic Agonists (levamisole, pyrantel, morantel and oxantel) that act on acetylcholine receptors of nematode somatic muscle; (2) The GABA Agonist, piperazine, that acts on nematode muscle GABA receptors; and (3) The Avermectins that open glutamate gated Cl- channels on nematode pharyngeal muscle. The electrophysiology and pharmacology of muscle and neuromuscular transmission the nematode parasite, Ascaris suum, is outlined and effects of anthelmintics that interfere with transmission described. Resistance to anthelmintics has appeared in some parasitic nematodes but the mechanisms of this resistance remain to be determined.

Oxantel-activated single channel currents in the muscle membrane of Ascaris suum.

The patch clamp technique was used to investigate the action of the anthelmintic drug, oxantel, on nicotinic acetylcholine receptor (nAChR) currents recorded from vesicles of the somatic muscle cells of the nematode parasite Ascaris suum. The amplitudes of the currents were analysed at different membrane potentials to determine the single channel conductance. Also the open and closed durations were measured to determine the kinetic properties of the activated channel. Oxantel activated single nAChR currents throughout a concentration range 10-100 microM, these currents were not observed with oxantel-free pipette solutions. The mean open time of the activated channels at a membrane potential of -75 mV and a concentration of 10 microM was 1.34 ms. At higher concentrations the open times were shorter and voltage sensitive, decreasing in duration on hyperpolarization, thus suggesting open channel block. The kinetics were analysed using a simple channel block model. The forward block rate, K + B, increased with increasing oxantel concentration but showed little increase as the membrane was hyperpolarized. K + B was 2.41 x 10(7) M-1 s-1 at -50 mV and 2.64 x 10(7) M-1 s-1 at -100 mV. The unblocking rate constant, K-B, did exhibit voltage sensitivity being 443.6 s-1 at -50 mV and 86.8 s-1 at -100 mV. Thus the blocking dissociation constant KB (= K-B/K + B) was 18.5 microM at -50 mV and 3.3 microM at -100 mV. The simple channel block scheme was found to be insufficient to explain fully the observations made; reasons for this are discussed.