Pharmacological interventions for self-harm in adults

Background : Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH, first published in 1998 and previously updated in 1999. We have now divided the review into three separate reviews. This review is focused on pharmacological interventions in adults who self harm. Objectives : To identify all randomised controlled trials of pharmacological agents or natural products for SH in adults, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., placebo/alternative pharmacological treatment) for SH patients. Search methods : For this update the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (September 2014). Additional searches of MEDLINE, EMBASE, PsycINFO, and CENTRAL were conducted to October 2013. Selection criteria : We included randomised controlled trials comparing pharmacological treatments or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months) episode of SH resulting in presentation to clinical services. Data collection and analysis : We independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Meta-analysis was only possible for one intervention (i.e. newer generation antidepressants) on repetition of SH at last follow-up. For this analysis, we pooled data using a random-effects model. The overall quality of evidence for the primary outcome was appraised for each intervention using the GRADE approach. Main results : We included seven trials with a total of 546 patients. The largest trial included 167 participants. We found no significant treatment effect on repetition of SH for newer generation antidepressants (n = 243; k = 3; OR 0.76, 95% CI 0.42 to 1.36; GRADE: low quality of evidence), low-dose fluphenazine (n = 53; k = 1; OR 1.51, 95% CI 0.50 to 4.58; GRADE: very low quality of evidence), mood stabilisers (n = 167; k = 1; OR 0.99, 95% CI 0.33 to 2.95; GRADE: low quality of evidence), or natural products (n = 49; k = 1; OR 1.33, 95% CI 0.38 to 4.62; GRADE: low quality of evidence). A significant reduction in SH repetition was found in a single trial of the antipsychotic flupenthixol (n = 30; k = 1; OR 0.09, 95% CI 0.02 to 0.50), although the quality of evidence for this trial, according to the GRADE criteria, was very low. No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported. Authors' conclusions : Given the low or very low quality of the available evidence, and the small number of trials identified, it is not possible to make firm conclusions regarding pharmacological interventions in SH patients. More and larger trials of pharmacotherapy are required. In view of an indication of positive benefit for flupenthixol in an early small trial of low quality, these might include evaluation of newer atypical antipsychotics. Further work should include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment

Numerical modelling of closed-cell aluminium foams under shock loading

The present research numerically investigates shock propagation through closed-cell aluminium foam via flyer-plate impact. The mechanics of foam deformation was elucidated using the finite element (FE) software ABAQUS/explicit. X-ray computed micro-tomography was performed to render a full 3D foam geometry mesh for understanding detailed macrostructural response due to shock propagation. Elastic wave propagation and pore collapse mechanism with time were studied. The free surface velocity of the foam was measured at two different flyer-plate impact velocities to observe the profile of the shock wave with time. Good correlations were observed between experimental data and FE predictions for both test conditionsThe authors gratefully acknowledge the laboratory facility provided by Department of Applied Mathematics, Australian National University. We also gratefully acknowledge the UNSW Canberra Defence Related Research Program that part-funded this work

Stress debriefing and patterns of recovery following a natural disaster

Stress debriefing has been used extensively following traumatic events; however, there is little evidence of its effectiveness. This paper reports the effects of stress debriefing on the rate of recovery of 195 helpers (e.g., emergency service personnel and disaster workers) following an earthquake in Newcastle, Australia (62 debriefed helpers and 133 who were not debriefed). Post-trauma stress reactions (Impact of Event Scale) and general psychological morbidity (General Health Questionnaire: GHQ-12) were assessed on four occasions over the first 2 years postearthquake. There was no evidence of an improved rate of recovery among those helpers who were debriefed, even when level of exposure and helping-related stress were taken into account. More rigorous investigation of the effectiveness of stress debriefing and its role in posttrauma recovery is urgently required

Pharmacological interventions for self-harm in adults

BackgroundSelf-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and strongly associated with suicide. This is an update of a broader Cochrane review on psychosocial and pharmacological treatments for deliberate SH, first published in 1998 and previously updated in 1999. We have now divided the review in to three separate reviews. This review is focused on pharmacological interventions in adults who self harm.ObjectivesTo identify all randomised controlled trials of pharmacological agents or natural products for SH in adults, and to conduct meta-analyses (where possible) to compare the effects of specific treatments with comparison types of treatment (e.g., placebo/alternative pharmacological treatment) for SH patients.Search methodsFor this update the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) Trials Search Co-ordinator searched the CCDAN Specialised Register (September 2014). Additional searches of MEDLINE, EMBASE, PsycINFO, and CENTRAL were conducted to October 2013.Selection criteriaWe included randomised controlled trials comparing pharmacological treatments or natural products with placebo/alternative pharmacological treatment in individuals with a recent (within six months) episode of SH resulting in presentation to clinical services.Data collection and analysisWe independently selected trials, extracted data, and appraised trial quality. For binary outcomes, we calculated odds ratios (ORs) and their 95% confidence intervals (CIs). For continuous outcomes we calculated the mean difference (MD) and 95% CI. Meta-analysis was only possible for one intervention (i.e. newer generation antidepressants) on repetition of SH at last follow-up. For this analysis, we pooled data using a random-effects model. The overall quality of evidence for the primary outcome was appraised for each intervention using the GRADE approach.Main resultsWe included seven trials with a total of 546 patients. The largest trial included 167 participants. We found no significant treatment effect on repetition of SH for newer generation antidepressants (n = 243; k = 3; OR 0.76, 95% CI 0.42 to 1.36; GRADE: low quality of evidence), low-dose fluphenazine (n = 53; k = 1; OR 1.51, 95% CI 0. 50 to 4.58; GRADE: very low quality of evidence), mood stabilisers (n = 167; k = 1; OR 0.99, 95% CI 0.33 to 2.95; GRADE: low quality of evidence), or natural products (n = 49; k = 1; OR 1.33, 95% CI 0.38 to 4.62; GRADE: low quality of evidence). A significant reduction in SH repetition was found in a single trial of the antipsychotic flupenthixol (n = 30; k = 1; OR 0.09, 95% CI 0.02 to 0.50), although the quality of evidence for this trial, according to the GRADE criteria, was very low. No data on adverse effects, other than the planned outcomes relating to suicidal behaviour, were reported.Authors&rsquo; conclusionsGiven the low or very low quality of the available evidence, and the small number of trials identified, it is not possible to make firm conclusions regarding pharmacological interventions in SH patients. More and larger trials of pharmacotherapy are required. In view of an indication of positive benefit for flupenthixol in an early small trial of low quality, these might include evaluation of newer atypical antipsychotics. Further work should include evaluation of adverse effects of pharmacological agents. Other research could include evaluation of combined pharmacotherapy and psychological treatment.<br /

Developmental brain trajectories in children with ADHD and controls: a longitudinal neuroimaging study

BACKGROUND: The symptom profile and neuropsychological functioning of individuals with Attention Deficit/Hyperactivity Disorder (ADHD), change as they enter adolescence. It is unclear whether variation in brain structure and function parallels these changes, and also whether deviations from typical brain development trajectories are associated with differential outcomes. This paper describes the Neuroimaging of the Children\u27s Attention Project (NICAP), a comprehensive longitudinal multimodal neuroimaging study. Primary aims are to determine how brain structure and function change with age in ADHD, and whether different trajectories of brain development are associated with variations in outcomes including diagnostic persistence, and academic, cognitive, social and mental health outcomes. METHODS/DESIGN: NICAP is a multimodal neuroimaging study in a community-based cohort of children with and without ADHD. Approximately 100 children with ADHD and 100 typically developing controls will be scanned at a mean age of 10 years (range; 9-11years) and will be re-scanned at two 18-month intervals (ages 11.5 and 13 years respectively). Assessments include a structured diagnostic interview, parent and teacher questionnaires, direct child cognitive/executive functioning assessment and magnetic resonance imaging (MRI). MRI acquisition techniques, collected at a single site, have been selected to provide optimized information concerning structural and functional brain development. DISCUSSION: This study will allow us to address the primary aims by describing the neurobiological development of ADHD and elucidating brain features associated with differential clinical/behavioral outcomes. NICAP data will also be explored to assess the impact of sex, ADHD presentation, ADHD severity, comorbidities and medication use on brain development trajectories. Establishing which brain regions are associated with differential clinical outcomes, may allow us to improve predictions about the course of ADHD

Psychosocial interventions for self-harm in adults

Background: Self-harm (SH; intentional self-poisoning or self-injury) is common, often repeated, and associated with suicide. This is an update of a broader Cochrane review first published in 1998, previously updated in 1999, and now split into three separate reviews. This review focuses on psychosocial interventions in adults who engage in self-harm.Objectives: To assess the effects of specific psychosocial treatments versus treatment as usual, enhanced usual care or other forms of psychological therapy, in adults following SH.Search methods: The Cochrane Depression, Anxiety and Neurosis Group (CCDAN) trials coordinator searched the CCDAN Clinical Trials Register (to 29 April 2015). This register includes relevant randomised controlled trials (RCTs) from: the Cochrane Library (all years), MEDLINE (1950 to date), EMBASE (1974 to date), and PsycINFO (1967 to date).Selection criteria: We included RCTs comparing psychosocial treatments with treatment as usual (TAU), enhanced usual care (EUC) or alternative treatments in adults with a recent (within six months) episode of SH resulting in presentation to clinical services.Data collection and analysis: We used Cochrane's standard methodological procedures

Treatment as usual (TAU) as a control condition in trials of cognitive behavioural-based psychotherapy for self-harm:impact of content and quality on outcomes in a systematic review

Background: Randomized controlled trials (RCTs) are the mainstay of evaluations of the efficacy of psychosocial interventions. In a recent Cochrane systematic review we analysed the efficacy of cognitive behavioural-based psychotherapies compared to treatment as usual (TAU) in adults who self-harm. In this study we examine the content and reporting quality of TAU in these trials and their relationship to outcomes. Methods: Five electronic databases (CCDANCTR-Studies and References, CENTRAL, MEDLINE, EMBASE, and PsycINFO) were searched for RCTs, indexed between 1 January 1998 and 30 April 2015, of cognitive-behavioural interventions compared to TAU for adults following a recent (within six months) episode of self-harm. Comparisons were made between outcomes for trials which included different categories of TAU, which were grouped as: multidisciplinary treatment, psychotherapy only, pharmacotherapy only, treatment by primary care physician, minimal contact, or unclear. Results: 18 trials involving 2433 participants were included. The content and reporting quality of TAU varied considerably between trials. The apparent effectiveness of cognitive behavioural psychotherapy varied according to TAU reporting quality and content. Specifically, effects in favour of cognitive-behavioural psychotherapy were strongest in trials in which TAU content was not clearly described (Odds Ratio: 0.29, 95% Confidence Interval 0.15–0.62; three trials) compared to those in which TAU comprised multidisciplinary treatment (Odds Ratio: 0.79, 95% CI 0.63 to 0.97; 12 trials). Limitations: The included trials had high risk of bias with respect to participant and clinical personnel blinding, and unclear risk of bias for selective outcome reporting. Conclusions: TAU content and quality represents an important source of heterogeneity between trials of psychotherapeutic interventions for prevention of self-harm. Before clinical trials begin, researchers should plan to carefully describe both aspects of TAU to improve the overall quality of investigations.</p

Identification of adults with symptoms suggestive of obstructive airways disease: Validation of a postal respiratory questionnaire

BACKGROUND: Two simples scoring systems for a self-completed postal respiratory questionnaire were developed to identify adults who may have obstructive airways disease. The objective of this study was to validate these scoring systems. METHOD: A two-stage design was used. All adults in two practice populations were sent the questionnaire and a stratified random sample of respondents was selected to undergo full clinical evaluation. Three respiratory physicians reviewed the results of each evaluation. A majority decision was reached as to whether the subject merited a trial of obstructive airways disease medication. This clinical decision was compared with two scoring systems based on the questionnaire in order to determine their positive predictive value, sensitivity and specificity. RESULTS: The PPV (positive predictive value) of the first scoring system was 75.1% (95% CI 68.6–82.3), whilst that of the second system was 82.3% (95% CI 75.9–89.2). The more stringent second system had the greater specificity, 97.1% (95% CI 96.0–98.2) versus 95.3% (95% CI 94.0–96.7), but poorer sensitivity 46.9% (95% CI 33.0–66.8) versus 50.3% (95% CI 35.3–71.6). CONCLUSION: This scoring system based on the number of symptoms/risk factors reported via a postal questionnaire could be used to identify adults who would benefit from a trial of treatment for obstructive airways disease

Relationship between atomoxetine plasma concentration, treatment response and tolerability in attention-deficit/hyperactivity disorder and comorbid oppositional defiant disorder

The purpose of this study was to examine whether atomoxetine plasma concentration predicts attention-deficit/hyperactivity disorder (ADHD) or oppositional defiant disorder (ODD) response. This post-hoc analysis assessed the relationship between atomoxetine plasma concentration and ADHD and ODD symptoms in patients (with ADHD and comorbid ODD) aged 6–12 years. Patients were randomly assigned to atomoxetine 1.2 mg/kg/day (n = 156) or placebo (n = 70) for 8 weeks (Study Period II). At the end of 8 weeks, ODD non-remitters (score >9 on the SNAP-IV ODD subscale and CGI-I > 2) with atomoxetine plasma concentration <800 ng/ml at 2 weeks were re-randomized to either atomoxetine 1.2 mg/kg/day or 2.4 mg/kg/day for an additional 4 weeks (Study Period III). ODD remitters and non-remitters with plasma atomoxetine ≥800 ng/ml remained on 1.2 mg/kg/day atomoxetine for 4 weeks. Patients who received atomoxetine, completed Study Period II, and entered Study Period III were included in these analyses. All the groups demonstrated improvement on the SNAP-IV ODD and ADHD-combined subscales (P < .001). At the end of Study Periods II and III, ODD and ADHD improvement was significantly greater in the remitter group compared with the non-remitter groups. Symptom improvement was numerically greater in the non-remitter (2.4 mg/kg/day compared with the non-remitter 1.2 mg/kg/day) group. Atomoxetine plasma concentration was not indicative of ODD and ADHD improvement after 12 weeks of treatment. ADHD and ODD symptoms improved in all the groups with longer duration on atomoxetine. Results suggest atomoxetine plasma concentration does not predict ODD and ADHD symptom improvement. However, a higher atomoxetine dose may benefit some patients