Reducing Self-harm in Adolescents. An individual participant data meta-analysis (RISA-IPD): systematic review protocol.

INTRODUCTION: Up to 10% of adolescents report self-harm in the previous year. Non-fatal repetition is common (18% in 1 year), death from any cause shows a fourfold and suicide a 10-fold excess. Despite the scale of the problem, there is insufficient evidence for effective interventions for self-harm. Those who self-harm do so for a variety of different reasons. Different treatments may be more effective for subgroups of adolescents; however, little is known about which subgroups are appropriate for further study. This protocol outlines a systematic review and individual participant data meta-analysis (IPD-MA) to identify subgroups of adolescents for which therapeutic interventions for self-harm show some evidence of benefit. METHODS AND ANALYSIS: A systematic literature search was conducted in August 2019 (including Cochrane Library, Embase, trial registers and other databases). An update search is planned. Study selection will identify randomised controlled trials examining interventions to reduce self-harm in adolescents who have self-harmed and presented to services. Identified research teams will be invited to contribute data and form a collaborative group. Two-stage IPD-MA will be used to evaluate effectiveness of different therapeutic interventions compared with any active or non-active control on repetition of self-harm, general psychopathology, depression, suicidal ideation, quality of life and death. Subgroup analyses will identify adolescent subgroups in whom different therapeutic interventions may be more effective. Meta-regression will explore moderating study and intervention effects. Sensitivity analyses will incorporate aggregate data from studies lacking IPD and test the robustness of results to methods for handling missing data, within-study clustering, non-adherence and study quality. ETHICS AND DISSEMINATION: Ethical approval is provided by the University of Leeds, Faculty of Medicine and Health Ethics Committee (18-098). Outcomes will inform research recommendations and will be disseminated internationally through the collaborative group, a service user advisory group, open-access peer-reviewed publication and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42019152119.

Randomised control trial of the effectiveness of an integrated psychosocial health promotion intervention aimed at improving health and reducing substance use in established psychosis (IMPaCT).

BACKGROUND: People with psychosis have a reduced life expectancy of 10-20 years, largely due to cardiovascular disease. This trial aimed to determine the effectiveness of a modular health promotion intervention (IMPaCT Therapy) in improving health and reducing cardiovascular risk in psychosis. METHODS: A multicentre, two arm, parallel cluster RCT was conducted across five UK mental health NHS trusts. Community care coordinators (CC) were randomly assigned to training and supervision in delivering IMPaCT Therapy or treatment as usual (TAU) to current patients with psychosis (cluster). The primary outcome was the physical and mental health subscales of the Short form-36 (SF-36) questionnaire. RESULTS: Of 104 care coordinators recruited, 52 (with 213 patients) were randomised to deliver IMPaCT therapy and 52 (with 193 patients) randomised to TAU. Of 406 patients, 318 (78%) and 301 (74%) attended 12- and 15-month follow-up respectively. IMPaCT therapy showed no significant effect on the physical or mental health component SF-36 scores versus TAU at 12 or 15 months. No effect was observed for cardiovascular risk indicators, except for HDL cholesterol, which improved more with IMPACT therapy than TAU (Treatment effect (95% CI); 0.085 (0.007 to 0.16); p = 0.034). The 22% of patients who received >180 min of IMPACT Therapy in addition to usual care achieved a greater reduction in waist circumference than did controls, which was clinically significant. CONCLUSION: Training and supervising community care coordinators to use IMPaCT therapy in patients with psychosis is insufficient to significantly improve physical or mental health quality of life. The search for effective, pragmatic interventions deliverable in health care services continues. TRIAL REGISTRATION: The trial was retrospectively registered with ISRCTN registry on 23/4/2010 at ISRCTN58667926 ; recruitment started on 01/03/2010 with first randomization on 09.08.2010 ISRCTN58667926 .

Randomised controlled trial to improve health and reduce substance use in established psychosis (IMPaCT): cost-effectiveness of integrated psychosocial health promotion.

BACKGROUND: There is mounting evidence that people with severe mental illness have unhealthy lifestyles, high rates of cardiovascular and metabolic diseases, and greater risk of early mortality. This study aimed to assess the cost-effectiveness of a health promotion intervention seeking to improve physical health and reduce substance use in people with psychosis. METHODS: Participants with a psychotic disorder, aged 18-65 years old and registered on an enhanced care approach programme or equivalent were recruited from community mental health teams in six mental health trusts in England. Participants were randomisation to either standard community mental health team care (treatment as usual) or treatment as usual with an integrated health promotion intervention (IMPaCT). Cost-effectiveness and cost-utility analyses from health and social care and societal perspectives were conducted alongside a cluster randomised controlled trial. Total health and social care costs and total societal costs at 12 and 15 months were calculated as well as cost-effectiveness (incremental cost-effectiveness ratios and cost-effectiveness acceptability curves) at 15 months based on quality of life (SF-36 mental and physical health components, primary outcome measures) and quality adjusted life years (QALYs) using two measures, EQ-5D-3 L and SF-36. Data were analysed using bootstrapped regressions with covariates for relevant baseline variables. RESULTS: At 12-15 months 301 participants had full data needed to be included in the economic evaluation. There were no differences in adjusted health and social care costs (£95, 95% CI -£1410 to £1599) or societal costs (£675, 95% CI -£1039 to £2388) between the intervention and control arms. Similarly, there were no differences between the groups in the SF-36 mental component (-0.80, 95% CI -3.66 to 2.06), SF-36 physical component (-0.68, 95% CI -3.01 to 1.65), QALYs estimated from the SF-36 (-0.00, -0.01 to 0.00) or QALYs estimated from the EQ-5D-3 L (0.00, 95% CI -0.01 to 0.02). Cost-effectiveness acceptability curves for all four outcomes and from both cost perspectives indicate that the probability of the health promotion intervention being cost-effective does not exceed 0.4 for willingness to pay thresholds ranging from £0-£50,000. CONCLUSIONS: Alongside no evidence of additional quality of life/clinical benefit, there is also no evidence of cost-effectiveness. TRIAL REGISTRATION: ISRCTN58667926 . Date retrospectively registered: 23/04/2010. Recruitment start date: 01/03/2010.

The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison.

BACKGROUND: Care for people with amyotrophic lateral sclerosis (ALS) has altered at King's College Hospital over the last 20 years. The clinic has been a multidisciplinary, specialist, tertiary referral centre since 1995 with a large team with integrated palliative and respiratory care since 2006. We hypothesised that these changes would improve survival. METHODS: In this retrospective observational study, patients diagnosed with El Escorial definite, probable and possible ALS between 1995-1998 and 2008-2011 were followed up. The primary outcome measure was a chi-square test for the proportion of each cohort surviving. Kaplan-Meier survival analysis and Cox multivariate regression were secondary analyses. RESULTS: There was low reporting of some interventions. Five hundred and forty-seven people were included. Survival between the cohorts was significantly different (p = 0.022) with a higher proportion surviving during 2008-2011. Survival time was 21.6 (95% CI 19.2-24.0) months in the 2008-2011 cohort compared to 19.2 years (15.6-21.6) in the 1995-1998 cohort (log rank p = 0.018). Four hundred and ninety-three cases were included in the Cox regression. Diagnostic cohort was a significant predictor variable (HR 0.79 (0.64-0.97) p = 0.023). CONCLUSIONS: These results support the hypothesis that integrated specialist clinics with multidisciplinary input improve survival in ALS.

Predictors of Treatment Outcome in Contextual Cognitive and Behavioral Therapies for Chronic Pain: A Systematic Review.

There is increasing evidence that contextual forms of cognitive-behavioral therapy (CBT) are effective in the management of chronic pain, yet little is understood about the factors that moderate or predict outcomes in these treatments. This systematic review aimed to identify pretreatment participant characteristics associated with positive treatment responses in contextual CBT for chronic pain. Medline, EMBASE, PsychINFO, and CENTRAL were searched to identify eligible studies. Studies were included if the participants were adults with chronic pain, designs were longitudinal, treatments focused on psychological flexibility or mindfulness, and reported results allowed for examination of moderators or predictors of standard treatment outcomes. Of 991 records initially identified, 20 were eligible for inclusion in the review. Some evidence suggested that baseline emotional functioning predicts treatment response, but the direction of this association varied between studies. Substantive findings were inconsistent and inconclusive, however, methodological limitations were consistent. These included treatment heterogeneity, and a lack of theoretical, a priori guidance in examining potential predictors. Future research should adopt a theoretically based approach to examining moderators in relation to specific treatment methods and therapeutic processes. Considering moderation without first considering mediation is probably a limited strategy. PERSPECTIVE: In this systematic review we examined evidence for potential predictors or moderators of outcomes in contextual CBT for chronic pain. Substantive findings were inconclusive but important methodological limitations and a lack of theoretical guidance were found. Future research should explicitly plan relevant methods and follow clear theoretical models.

Real-time fMRI neurofeedback in adolescents with attention deficit hyperactivity disorder.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. Real-time functional magnetic resonance neurofeedback (rtfMRI-NF) allows participants to gain self-control over dysregulated brain regions. Despite evidence for beneficial effects of electrophysiological-NF on ADHD symptoms, no study has applied the spatially superior rtfMRI-NF neurotherapy to ADHD. A randomized controlled trial tested the efficacy of rtfMRI-NF of right inferior prefrontal cortex (rIFG), a key region that is compromised in ADHD and upregulated with psychostimulants, on improvement of ADHD symptoms, cognition, and inhibitory fMRI activation. To control for region-specificity, an active control group received rtfMRI-NF of the left parahippocampal gyrus (lPHG). Thirty-one ADHD boys were randomly allocated and had to learn to upregulate their target brain region in an average of 11 rtfMRI-NF runs over 2 weeks. Feedback was provided through a video-clip of a rocket that had to be moved up into space. A transfer session without feedback tested learning retention as a proximal measure of transfer to everyday life. Both NF groups showed significant linear activation increases with increasing number of runs in their respective target regions and significant reduction in ADHD symptoms after neurotherapy and at 11-month follow-up. Only the group targeting rIFG, however, showed a transfer effect, which correlated with ADHD symptom reductions, improved at trend level in sustained attention, and showed increased IFG activation during an inhibitory fMRI task. This proof-of-concept study demonstrates for the first time feasibility, safety, and shorter- and longer-term efficacy of rtfMRI-NF of rIFG in adolescents with ADHD. Hum Brain Mapp 38:3190-3209, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Therapeutic interventions for suicide attempts and self-harm in adolescents: systematic review and meta-analysis.

OBJECTIVE: Suicidal behavior and self-harm are common in adolescents and are associated with elevated psychopathology, risk of suicide, and demand for clinical services. Despite recent advances in the understanding and treatment of self-harm and links between self-harm and suicide and risk of suicide attempt, progress in reducing suicide death rates has been elusive, with no substantive reduction in suicide death rates over the past 60 years. Extending prior reviews of the literature on treatments for suicidal behavior and repetitive self-harm in youth, this article provides a meta-analysis of randomized controlled trials (RCTs) reporting efficacy of specific pharmacological, social, or psychological therapeutic interventions (TIs) in reducing both suicidal and nonsuicidal self-harm in adolescents. METHOD: Data sources were identified by searching the Cochrane, Medline, PsychINFO, EMBASE, and PubMed databases as of May 2014. RCTs comparing specific therapeutic interventions versus treatment as usual (TAU) or placebo in adolescents (through age 18 years) with self-harm were included. RESULTS: Nineteen RCTs including 2,176 youth were analyzed. TIs included psychological and social interventions and no pharmacological interventions. The proportion of the adolescents who self-harmed over the follow-up period was lower in the intervention groups (28%) than in controls (33%) (test for overall effect z = 2.31; p = .02). TIs with the largest effect sizes were dialectical behavior therapy (DBT), cognitive-behavioral therapy (CBT), and mentalization-based therapy (MBT). There were no independent replications of efficacy of any TI. The pooled risk difference between TIs and TAU for suicide attempts and nonsuicidal self-harm considered separately was not statistically significant. CONCLUSION: TIs to prevent self-harm appear to be effective. Independent replication of the results achieved by DBT, MBT, and CBT is a research priority.

The effects of hypothermia and L-arginine on skeletal muscle function in ischemia-reperfusion injury.

OBJECTIVES: Ischemia-reperfusion (I/R) injury can have detrimental effects on skeletal muscle. We have shown that vessel permeability can be minimized in a hypothermic setting and also by administering the nitric oxide synthase (NOS) stimulator, L-arginine, at physiologic temperatures. The purpose of this study was to examine and compare skeletal muscle contractility after an I/R insult during hypothermic conditions, warm conditions, and also with the administration of L-arginine at physiologic temperatures. We hypothesized that hypothermia and L-arginine administration will also demonstrate protective effects to skeletal muscle contractility. METHODS: Using Sprague-Dawley rats, the extensor digitorum longus muscle was rotated on its vascular pedicle to a thermo-controlled stage. Ischemia was established using an atraumatic femoral artery tourniquet. Reperfusion was performed under control and experimental conditions including local hypothermia and intravenous L-arginine. After harvesting experimental muscles, contractility was then quantified by using a tissue bath stimulator with force transducers. RESULTS: Warm reperfusion resulted in marked decrease in muscle contractility compared with sham animals. Local hypothermia showed statistically significant preservation of contractility compared with the sham group. This protective effect was recapitulated by the application of NOS inducers (L-arginine) at warm conditions. CONCLUSIONS: These findings demonstrate that hypothermia and L-arginine are protective of skeletal muscle contractility after an I/R injury. The results presented may have profound effects on future therapeutic recommendations and suggest possible pathways for clinical intervention to modulate I/R injury, which is commonplace in orthopaedic trauma and reconstructive surgery.