Mailed treatment to augment primary care for alcohol disorders : a randomised controlled trial

Introduction and Aims: Remote delivery of interventions is needed to address large numbers of people with alcohol use disorders who are spread over large areas. Previous correspondence trials typically examined its effects as stand-alone treatment. This study aimed to test whether adding postal treatment to general practitioner (GP) support would lower alcohol use more than GP intervention alone. Design and Methods: A single-blind, randomised controlled trial with a crossover design was conducted over 12 months on 204 people with alcohol use disorders. Participants in an immediate correspondence condition received treatment over the first 3 months; those receiving delayed treatment received it in months 3–6. Results: Few participants were referred from GPs, and little intervention was offered by them. At 3 months, 78% of participants remained in the study. Those in immediate treatment showed greater reductions in alcohol per week, drinking days, anxiety, depression and distress than those in the delayed condition. However, post-treatment and follow-up outcomes still showed elevated alcohol use, depression, anxiety and distress. Greater baseline anxiety predicted better alcohol outcomes, although more mental distress at baseline predicted dropout. Discussion and Conclusions: The study gave consistent results with those from previous research on correspondence treatments, and showed that high levels of participant engagement over 3 months can be obtained. Substantial reductions in alcohol use are seen, with indications that they are well maintained. However, many participants continue to show high-risk alcohol use and psychological distress.

Psychological treatment dropout among pathological gamblers

Premature dropout from treatments for pathological gambling is potentially of significant importance, if it occurs before substantial progress has been made in addressing the problem. A systematic review of current research on dropout from psychological treatments for pathological gambling identified 12 studies from five countries. Dropout ranged from 14% to 50%, with a median of dropout 26%. Overall, 31% of the participants dropped out of treatment. Few studies distinguish between dropouts at different stages of participation. The evidence on specific variables that predict dropout is limited or inconsistent, and is characterised by a lack of a coherent, gambling-specific model and by methodological problems. Two studies that attempted to apply motivational and compliance-enhancing techniques were found. Both showed promising effects on reduction of dropout and improvement of short-term impact of treatment, but inconsistent results on longer-term outcomes were obtained. The review highlighted a need for more rigorous investigation of the extent of dropout and of variables associated with dropout from pathological gambling treatment programs. Further research on interventions to enhance retention and reduce dropout from psychological treatment is also required.

Current evidence on integrated treatment for serious mental disorder and substance misuse

Substance misuse in people with serious mental disorders is common and has a wideranging negative impact. The multiplicity of problems suggests that this comorbidity is better conceptualized as a type of complex disorder than by ‘dual diagnosis’. Problems with sequential and parallel treatments have led to the development of integrated approaches, with one practitioner or team addressing both the substance use and mental disorder. These treatments are typically characterized by motivation enhancement, minimizing treatment-related stress, emphasizing harm reduction as well as abstinence, and assertive outreach. A review of published randomized trials demonstrates that superior effects to controls are rarely consistent across treatment foci and over time. While motivational interventions assist engagement, more intervention is usually required for integrated treatment programs to improve long-term outcomes more than control conditions. More intensive case management does not consistently improve impact, but extended cognitive-behavioral therapies have promise. Suggestions for maximizing treatment effects and improving research evidence are provided.

Vitreous cryopreservation of nanofibrous tissue-engineered constructs generated using mesenchymal stromal cells

Development of an effective preservation strategy to fulfill off-the-shelf availability of tissue-engineered constructs (TECs) is demanded for realizing their clinical potential. In this study, the feasibility of vitrification, ice-free cryopreservation, for precultured ready-to-use TECs was evaluated. To prepare the TECs, bone marrow-derived porcine mesenchymal stromal cells (MSCs) were seeded in polycaprolactone-gelatin nanofibrous scaffolds and cultured for 3 weeks before vitrification treatment. The vitrification strategy developed, which involved exposure of the TECs to low concentrations of cryoprotectants followed by a vitrification solution and sterile packaging in a pouch with its subsequent immersion directly into liquid nitrogen, was accomplished within 11min. Stepwise removal of cryoprotectants, after warming in a 38 degrees C water bath, enabled rapid restoration of the TECs. Vitrification did not impair microstructure of the scaffold or cell viability. No significant differences were found between the vitrified and control TECs in cellular metabolic activity and proliferation on matched days and in the trends during 5 weeks of continuous culture postvitrification. Osteogenic differentiation ability in vitrified and control groups was similar. In conclusion, we have developed a time- and cost-efficient cryopreservation method that maintains integrity of the TECs while preserving MSCs viability and metabolic activity, and their ability to differentiate.

Mechanisms of improvement in treatment for depression : test of a self-efficacy and performance model

Tested D. J. Kavanagh's (1983) depression model's explanation of response to cognitive-behavioral treatment among 19 20–60 yr old Ss who received treatment and 24 age-matched Ss who were assigned to a waiting list. Measures included the Beck Depression Inventory and self-efficacy (SE) and self-monitoring scales. Rises in SE and self-monitored performance of targeted skills were closely associated with the improved depression scores of treated Ss. Improvements in the depression of waiting list Ss occurred through random, uncontrolled events rather than via a systematic increase in specific skills targeted in treatment. SE regarding assertion also predicted depression scores over a 12-wk follow-up.

Effectiveness of current treatment approaches for benzodiazepine discontinuation : a meta-analysis.

Aims: To assess the effectiveness of current treatment approaches to assist benzodiazepine discontinuation. Methods: A systematic review of approaches to benzodiazepine discontinuation in general practice and out-patient settings was undertaken. Routine care was compared with three treatment approaches: brief interventions, gradual dose reduction (GDR) and psychological interventions. GDR was compared with GDR plus psychological interventions or substitutive pharmacotherapies. Results: Inclusion criteria were met by 24 studies, and a further eight were identified by future search. GDR [odds ratio (OR) = 5.96, confidence interval (CI) = 2.08–17.11] and brief interventions (OR = 4.37, CI = 2.28–8.40) provided superior cessation rates at post-treatment to routine care. Psychological treatment plus GDR were superior to both routine care (OR = 3.38, CI = 1.86–6.12) and GDR alone (OR = 1.82, CI = 1.25–2.67). However, substitutive pharmacotherapies did not add to the impact of GDR (OR = 1.30, CI = 0.97– 1.73), and abrupt substitution of benzodiazepines by other pharmacotherapy was less effective than GDR alone (OR = 0.30, CI = 0.14–0.64). Few studies on any technique had significantly greater benzodiazepine discontinuation than controls at follow-up. Conclusions: Providing an intervention is more effective than routine care. Psychological interventions may improve discontinuation above GDR alone. While some substitutive pharmacotherapies may have promise, current evidence is insufficient to support their use.

Substance Treatment Options in Psychosis (STOP) : a new intervention for dual diagnosis

Despite the high co-occurrence of psychosis and substance abuse, there is very little research on the development of effective treatments for this problem. This paper describes a new intervention that facilitates reaching functional goals through collaboration between therapists, participants and families. Substance Treatment Options in Psychosis (STOP) integrates pharmacological and psycho-logical treatments for psychotic symptoms, with cognitive-behavioural approaches to substance abuse. STOP is tailored to participants' problems and abilities, and recognises that control of consumption and even engagement may take several attempts. Training in relevant skills is augmented by bibliotherapy, social support and environmental change. A case description illustrates the issues and challenges in implementation.

Eye-movements and visual imagery : a working memory approach to the treatment of post-traumatic stress disorder

It has been claimed that the symptoms of post-traumatic stress disorder (PTSD) can be ameliorated by eye-movement desensitization-reprocessing therapy (EMD-R), a procedure that involves the individual making saccadic eye-movements while imagining the traumatic event. We hypothesized that these eye-movements reduce the vividness of distressing images by disrupting the function of the visuospatial sketchpad (VSSP) of working memory, and that by doing so they reduce the intensity of the emotion associated with the image. This hypothesis was tested by asking non-PTSD participants to form images of neutral and negative pictures under dual task conditions. Their images were less vivid with concurrent eye-movements and with a concurrent spatial tapping task that did not involve eye-movements. In the first three experiments, these secondary tasks did not consistently affect participants' emotional responses to the images. However, Expt 4 used personal recollections as stimuli for the imagery task, and demonstrated a significant reduction in emotional response under the same dual task conditions. These results suggest that, if EMD-R works, it does so by reducing the vividness and emotiveness of traumatic images via the VSSP of working memory. Other visuospatial tasks may also be of therapeutic value.

EMG biofeedback in the treatment of tinnitus : an experimental evaluation

26 tinnitus patients received either electromyogram (EMG) biofeedback with counterdemand instructions, EMG biofeedback with neutral demand instructions, or no treatment. Assessment was conducted on self-report measures of the distress associated with tinnitus, the loudness, annoyance and awareness of tinnitus, sleep-onset difficulties, depression, and anxiety. Audiological assessment of tinnitus was also conducted and EMG levels were measured (the latter only in the 2 treatment groups). No significant treatment effects were found on any of the measures. There was a significant decrease in the ratings of tinnitus awareness over the assessment occasions, but the degree of change was equivalent for treated and untreated groups. Results do not support the assertion that EMG biofeedback is an effective treatment for tinnitus.

Duty of police and ambulance services : what happens when the plaintiff refuses treatment?

In a recent case the New South Wales Court of Appeal considered the duty of care owed by ambulance and police officers, issues concerning breach and causation and the practical effect of the exclusion of the plaintiff's evidence.

What is the future for rimonabant in the treatment of obesity

Orlistat and sibutramine only cause modest reductions in body weight. Rimonabant, a cannabinoid receptor 1 antagonist, is a new approach to weight reduction, but is it safe, efficacious, and better than the existing agents?

Telcagepant is a new oral treatment for migraine

Background : Migraine is a common cause of disability. Many subjects (30 – 40%) do not respond to the 5-HT 1B/1D agonists (the triptans) commonly used in the treatment of migraine attacks. Calcitonin gene-related protein (CGRP) receptor antagonism is a new approach to the treatment of migraine attacks. Objectives/methods : This evaluation is of a Phase III clinical trial comparing telcagepant, an orally active CGRP receptor antagonist, with zolmitriptan in subjects during an attack of migraine. Results : Telcagepant 300 mg has a similar efficacy to zolmitriptan in relieving pain, phonophobia, photophobia, and nausea. Telcagepant was better tolerated than zolmitriptan. Conclusions : The initial Phase III clinical trial results with telcagepant are promising but several further clinical trials are needed to determine the place of telcagepant in the treatment of migraine attacks

Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.