Overview: Beyond guidelines and guidance—psychosocial perspectives on treatment interventions for young people with substance problems in the United Kingdom

Over the last two decades there has been accumulating evidence that both psychosocial and pharmacological treatment interventions can effect change in substance-misusing adults. Thus, treatment interventions implemented for young people with substance problems largely draw on the adult addiction experience and that of child and adolescent psychiatry and psychology. As young people with problematic drug use have different treatment needs, and require different interventions and services to those of adults, results of adult studies cannot necessarily be directly extrapolated to young people.

Over the last five years evidence has been rapidly mounting that treatment may potentially work in young people, but as yet it is not as extensive as that for adults. The interventions that appear most fruitful are those based on learning theory, e.g. cognitive behavioural therapy and family therapy. Outcome studies in young people demonstrate substantial variability in substance use and misuse following treatment. From the UK perspective, the evidence is almost entirely USA based, and these evaluations of non-UK treatment programmes for young people cannot be simply transferred or transported to UK healthcare settings. This has significant implications for practice and policy.

At this stage, 'guidelines' or 'guidance' that is available is either not directed at young people and/or is largely gleaned from the USA literature. In addition, it does not adequately capture the complexity of cases at front-line specialist settings. The management of young substance misusers in the UK is, in the main, 'beyond guidelines and guidance'.

The restricted treatment service network for young people in the UK makes the potential for undertaking studies on treatment effectiveness extremely limited, but because there is evidence of a growing number of young people requiring treatment, such specialist drug services require evaluation. Serious consideration of the establishment and funding of evaluation of treatment interventions to be delivered to young substance misusers in the UK is urgently needed.     

Indomethacin and cognitive function in healthy elderly volunteers.

1. The aim of this randomised, double-blind four way crossover study was to assess the interaction between the new calcium antagonist, lacidipine and atenolol, in patients with mild to moderate hypertension. 2. Sitting blood pressure at 4 h post-dosing with lacidipine (4 mg) and atenolol (100 mg) alone was significantly lower compared with placebo (137/89 +/- 3/3 mmHg; 142/89 +/- 5/3 mmHg; and 154/98 +/- 5/3 mmHg respectively; P < 0.001). Co-administration of both drugs produced a significant additive effect compared with atenolol and lacidipine alone (124/80 +/- 4/2 mmHg; P < 0.002). 3. Heart rate on treatment with lacidipine alone was significantly greater at 4 h compared with placebo (86 +/- 1 beats min-1 and 74 +/- 2 beats min-1 respectively; P < 0.001). When both drugs were used in combination, there was a significant decrease in pulse rate compared with lacidipine alone (58 +/- 1 beats min-1 and 86 +/- 1 beats min-1 respectively; P < 0.001). 4. Home blood pressure recordings confirmed the statistically significant reduction in blood pressure on co-dosing (120/82 +/- 10/2 mmHg) compared with lacidipine (140/92 +/- 5/3 mmHg) and atenolol (146/90 +/- 6/3 mmHg) given alone (P < 0.05). 5. Lacidipine alone produced a significant exercise tachycardia compared with atenolol alone and the atenolol/lacidipine combination (97 +/- 8 beats min-1; 65 +/- 4 beats min-1 and 75 +/- 7 beats min-1 respectively; P < 0.001). Exercise tolerance was not adversely affected by the co-administration of both lacidipine and atenolol.     

Effect of delayed administration of activated charcoal on nortriptyline absorption

Summary Activated charcoal is known to reduce the absorption of therapeutic doses of nortriptyline in vivo when administered 30 min after drug ingestion. In a group of volunteers, one sachet (10 g) of a new activated charcoal preparation, Medicoal was found to produce a highly significant reduction in nortriptyline absorption when given as long as four hours after nortriptyline dosing. Activated charchoal may therefore be useful in the treatment of tricyclic antide-pressant poisoning even if a delay of several hours ensues before medical help is sought.     

Metabolic and flow correlates of myocardial ischaemia

Seven hundred and twenty three biopsies were obtained from 20 dogs after coronary artery ligation for 5, 30, 45, 60 or 120 min (n = 4 dogs for each group). Paired values for blood flow (radioactive microspheres) and tissue ATP content were obtained for each biopsy and related to the duration of ischaemia. Three states of ischaemic injury could be recognised. In the first, designated as "tolerable" ischaemia, coronary flow was reduced by up to 50%. In this flow band, ATP depletion was relatively small and time-independent. If flow was reduced by 60 to 80%, a state of "critical" ischaemia was identified where ATP depletion was both flow- and time-dependent and, in this relatively narrow range, small changes in flow or duration could result in major changes in ATP depletion. With severe flow reductions of greater than 80%, designated as "lethal" ischaemia, a complex pattern emerged such that with up to 30 min of ischaemia, ATP fell progressively with increasing time and flow deprivation. Between 30 and 45 min ATP depletion accelerated and beyond 45 min the time-dependency disappeared with tissue ATP content remaining relatively constant at a severely depressed level for several hours. All of these results are discussed in the light of earlier proposals (disputed) that tissue injury as expressed by ATP depletion can be predicted by the product of ischaemic duration and flow deprivation.     

Angiogenesis is an early event in the development of chemically induced skin tumors

In this study we have analyzed the vascular response induced in the two- stage carcinogenesis model in SENCAR mice. The role of angiogenesis has not been explored in this model, which is the paradigm of multistage carcinogenesis and a model for neoplastic lesions derived from exophytic premalignant lesions (e.g. colon carcinoma, bladder papilloma). We investigated if angiogenesis is involved in the formation of papillomas and in the progression from papilloma to carcinoma. To this end we analyzed the vasculature of normal and hyperplastic skin, focal epidermal hyperplasias that are precursors of papillomas, papillomas at different stages and squamous cell carcinomas. We also analyzed the vascularization of papillomas induced in two strains of mice that differ in their susceptibility to malignant progression. We show here that angiogenesis is turned on in the earliest stages of papilloma formation. In late stages, regardless of state of progression, the predominant response is an increase in the size of blood vessels. Thus, in the SENCAR mouse model, representative of exophytic tumors, the angiogenesis switch is a very early event, probably mechanistically related to the development of the primarily exophytic lesions. Therefore, the density of blood vessels cannot be used as a predictor of malignant progression in this model.      

Calcium antagonists and myocardial protection: a comparative study of the functional, metabolic and electrical consequences of verapamil and nifedipine as additives to the St. Thomas' cardioplegic solution

Using an isolated rat heart preparation as a model of cardiopulmonary bypass and ischemic arrest, a comparative study has been undertaken in order to characterize the functional, metabolic and electrophysiological consequences resulting from the addition of dl-verapamil or nifedipine to the St. Thomas' Hospital cardioplegic solution. Hearts (n = 6 in each group) were subjected to cardioplegic infusion with the St. Thomas' solution with or without added verapamil (1.1 micromoles/liter) or nifedipine (0.075 micromoles/liter). After 35 minutes of normothermic (37 degrees C) ischemic arrest, reperfusion was initiated and functional recovery was measured and expressed as a percent of its pre-ischemic control value. Inclusion of nifedipine in the cardioplegic solution improved the post-ischemic recovery of cardiac output from its control value of 59.8 +/- 3.0% to 80.0 +/- 2.5%. The temporal characteristics for the post-ischemic recovery of electrical activity and contractile performance were uncomplicated and similar to control hearts. Inclusion of verapamil also improved the protective properties of the St. Thomas' solution with cardiac output recovering to 76.8% +/- 2.8%. However, in contrast to the control and nifedipine groups, the profile for functional recovery was complex. After an early initial recovery, pressure development declined for 0.5 to 6.0 minutes. This occurred despite the recovery of electrical activity. Hearts then exhibited a second phase of recovery where pressure development returned to normal and this was sustained for the duration of the experiment. Analysis of electrocardiographic characteristics revealed a significant prolongation of the P-P and P-Q interval during the first 10 minutes of reperfusion in the verapamil group.(ABSTRACT TRUNCATED AT 250 WORDS)