The provision of services in the UK for UK armed forces veterans with PTSD : a rapid evidence synthesis

Background Our research arises from anticipated increases in demand for psychological trauma services in the UK, with particular reference to armed forces veterans with post-traumatic stress disorder (PTSD). Commissioning and service provider activity to improve veterans’ health is evolving. Objectives To explore what UK services exist and establish potentially effective models of care and effective treatments for armed forces veterans with PTSD. Design A four-stage rapid evidence synthesis comprising information gathering on UK service provision; an evidence review on models of care; a metareview on treatment effectiveness; and a synthesis highlighting research priorities. Setting For the evidence reviews, any setting that was relevant to the UK health and social care system. Participants UK armed forces veterans with PTSD following repeated exposure to traumatic events. Interventions Any model of care or treatment. Main outcome measures Any relevant outcome. Data sources Information about current UK practice. Searches of databases [including MEDLINE, PsycINFO and PILOTS (Published International Literature on Traumatic Stress)], guidelines and relevant websites, up to November 2016. Review methods We screened titles and abstracts using EPPI-Reviewer 4 (EPPI-Centre, Social Science Research Unit, Institute of Education, University of London, UK) and EndNote X7 [Clarivate Analytics (formerly Thomson Reuters), Philadelphia, PA, USA]. Decisions to include papers were made by two reviewers independently. We conducted a narrative synthesis of research literature on models of care and on treatments, guided by information from UK practice. In our evidence reviews, we assessed (when appropriate) the quality of included studies using established criteria. To help interpret our findings, we consulted recently published public and patient involvement data, a veteran service user and experts with academic, military and commissioning backgrounds. Results We gathered information about current UK practice. Sixty-one studies were included in the rapid evidence review on models of care and seven systematic reviews in the rapid metareview of treatments. The quality of evidence in both evidence reviews was limited. Promising models of care from more robust studies (three randomised controlled trials and one qualitative study) were collaborative arrangements and community outreach for improving intervention access and uptake; integrated mental health services and behavioural intervention on increased smoking abstinence; and peer support as an acceptable complement to PTSD treatment. A poor fit was noted between the research literature and UK service provision. Promising treatments were psychosocial interventions (eye movement desensitisation and reprocessing, cognitive processing therapy, trauma-focused and exposure-based intervention) and pharmacotherapy (selective serotonin reuptake inhibitors, antidepressants, anticonvulsants, antipsychotics) for improving PTSD and mental health symptoms. Limitations The literature pool was larger than anticipated. Evidence for potentially effective models of care and potentially effective treatments is limited in quality and quantity. Although we aimed for a comprehensive evidence synthesis, pragmatic decisions in searching, screening and inclusion of studies may mean that relevant studies were overlooked. Conclusions There is tentative support for the effectiveness of some models of care and certain treatments currently delivered in UK practice. Our findings are timely for commissioners and service providers when developing present activity in veterans’ health care. Future work We report potential implications for future health-care practice, including early intervention for veterans transitioning from military life, improving general practitioners’ knowledge about services, implementing needs-based service design and tackling wider-system challenges. Regarding potential areas of future research, we have identified the need for more-robust (and longer) evaluative studies in the UK setting. Funding The National Institute for Health Research Health Services and Delivery Research programme

Digital interventions for generalised anxiety disorder (GAD) : systematic review and network meta-analysis

Background: Generalized anxiety disorder is the most common mental health condition based on weekly prevalence. Digital interventions have been used as alternatives or as supplements to conventional therapies to improve access, patient choice, and clinical outcomes. Little is known about their comparative effectiveness for generalized anxiety disorder. Methods: We conducted a systematic review and networkmeta-analysis of randomized controlled trials comparing digital interventions with medication, non-digital interventions, non-therapeutic controls, and no intervention. Results: We included 21 randomized controlled trials with a total of 2,350 participants from generalized anxiety disorder populations. Pooled outcomes using analysis of Covariance and rankograms based on the surface under the cumulative ranking curves indicated that antidepressant medication and group therapy had a higher probability than digital interventions of being the “best” intervention. Supported digital interventions were not necessarily “better” than unsupported (pure self-help) ones. Conclusions: Due to very wide confidence intervals, network meta-analysis results were inconclusive as to whether digital interventions are better than no intervention and non-therapeutic active controls, or whether they confer an additional benefit to standard therapy. Future research needs to compare digital interventions with one-to-one therapy and with manualized non-digital self-help and to include antidepressant medication as a treatment comparator and effect modifier

EarlyCDT Lung blood test for risk classification of solid pulmonary nodules : systematic review and economic evaluation

BACKGROUND: EarlyCDT Lung (Oncimmune Holdings plc, Nottingham, UK) is a blood test to assess malignancy risk in people with solid pulmonary nodules. It measures the presence of seven lung cancer-associated autoantibodies. Elevated levels of these autoantibodies may indicate malignant disease. The results of the test might be used to modify the risk of malignancy estimated by existing risk calculators, including the Brock and Herder models. OBJECTIVES: The objectives were to determine the diagnostic accuracy, clinical effectiveness and cost-effectiveness of EarlyCDT Lung; and to develop a conceptual model and identify evidence requirements for a robust cost-effectiveness analysis. DATA SOURCES: MEDLINE (including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily and Ovid MEDLINE), EMBASE, Cochrane Central Register of Controlled Trials, Science Citation Index, EconLit, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment database, NHS Economic Evaluation Database ( NHS EED ) and the international Health Technology Assessment database were searched on 8 March 2021. REVIEW METHODS: A systematic review was performed of evidence on EarlyCDT Lung, including diagnostic accuracy, clinical effectiveness and cost-effectiveness. Study quality was assessed with the quality assessment of diagnostic accuracy studies-2 tool. Evidence on other components of the pulmonary nodule diagnostic pathway (computerised tomography surveillance, Brock risk, Herder risk, positron emission tomography-computerised tomography and biopsy) was also reviewed. When feasible, bivariate meta-analyses of diagnostic accuracy were performed. Clinical outcomes were synthesised narratively. A simulation study investigated the clinical impact of using EarlyCDT Lung. Additional reviews of cost-effectiveness studies evaluated (1) other diagnostic strategies for lung cancer and (2) screening approaches for lung cancer. A conceptual model was developed. RESULTS: A total of 47 clinical publications on EarlyCDT Lung were identified, but only five cohorts (695 patients) reported diagnostic accuracy data on patients with pulmonary nodules. All cohorts were small or at high risk of bias. EarlyCDT Lung on its own was found to have poor diagnostic accuracy, with a summary sensitivity of 20.2% (95% confidence interval 10.5% to 35.5%) and specificity of 92.2% (95% confidence interval 86.2% to 95.8%). This sensitivity was substantially lower than that estimated by the manufacturer (41.3%). No evidence on the clinical impact of EarlyCDT Lung was identified. The simulation study suggested that EarlyCDT Lung might potentially have some benefit when considering intermediate risk nodules (10-70% risk) after Herder risk analysis. Two cost-effectiveness studies on EarlyCDT Lung for pulmonary nodules were identified; none was considered suitable to inform the current decision problem. The conceptualisation process identified three core components for a future cost-effectiveness assessment of EarlyCDT Lung: (1) the features of the subpopulations and relevant heterogeneity, (2) the way EarlyCDT Lung test results affect subsequent clinical management decisions and (3) how changes in these decisions can affect outcomes. All reviewed studies linked earlier diagnosis to stage progression and stage shift to final outcomes, but evidence on these components was sparse. LIMITATIONS: The evidence on EarlyCDT Lung among patients with pulmonary nodules was very limited, preventing meta-analyses and economic analyses. CONCLUSIONS: The evidence on EarlyCDT Lung among patients with pulmonary nodules is insufficient to draw any firm conclusions as to its diagnostic accuracy or clinical or economic value. FUTURE WORK: Prospective cohort studies, in which EarlyCDT Lung is used among patients with identified pulmonary nodules, are required to support a future assessment of the clinical and economic value of this test. Studies should investigate the diagnostic accuracy and clinical impact of EarlyCDT Lung in combination with Brock and Herder risk assessments. A well-designed cost-effectiveness study is also required, integrating emerging relevant evidence with the recommendations in this report. STUDY REGISTRATION: This study is registered as PROSPERO CRD42021242248. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 49. See the NIHR Journals Library website for further project information

Interventions for Complex Traumatic Events (INCiTE): Systematic review and research prioritisation exercise

Background: People with a history of complex traumatic events typically experience trauma and stressor disorders and additional mental comorbidities. It is not known if existing evidence-based treatments are effective and acceptable for this group of people. Objective: To identify candidate psychological and non-pharmacological treatments for future research. Design: Mixed-methods systematic review. Participants: Adults aged 65 18 years with a history of complex traumatic events. Interventions: Psychological interventions versus control or active control; pharmacological interventions versus placebo. Main outcome measures: Post-traumatic stress disorder symptoms, common mental health problems and attrition. Data sources: Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 onwards); Cochrane Central Register of Controlled Trials (CENTRAL) (from inception); EMBASE (1974 to 2017 week 16); International Pharmaceutical Abstracts (1970 onwards); MEDLINE and MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations (1946 to present); Published International Literature on Traumatic Stress (PILOTS) (1987 onwards); PsycINFO (1806 to April week 2 2017); and Science Citation Index (1900 onwards). Searches were conducted between April and August 2017. Review methods: Eligible studies were singly screened and disagreements were resolved at consensus meetings. The risk of bias was assessed using the Cochrane risk-of-bias tool and a bespoke version of a quality appraisal checklist used by the National Institute for Health and Care Excellence. A meta-analysis was conducted across all populations for each intervention category and for population subgroups. Moderators of effectiveness were assessed using metaregression and a component network meta-analysis. A qualitative synthesis was undertaken to summarise the acceptability of interventions with the relevance of findings assessed by the GRADE-CERQual checklist. Results: One hundred and four randomised controlled trials and nine non-randomised controlled trials were included. For the qualitative acceptability review, 4324 records were identified and nine studies were included. The population subgroups were veterans, childhood sexual abuse victims, war affected, refugees and domestic violence victims. Psychological interventions were superior to the control post treatment for reducing post-traumatic stress disorder symptoms (standardised mean difference -0.90, 95% confidence interval -1.14 to -0.66; number of trials = 39) and also for associated symptoms of depression, but not anxiety. Trauma-focused therapies were the most effective interventions across all populations for post-traumatic stress disorder and depression. Multicomponent and trauma-focused interventions were effective for negative self-concept. Phase-based approaches were also superior to the control for post-traumatic stress disorder and depression and showed the most benefit for managing emotional dysregulation and interpersonal problems. Only antipsychotic medication was effective for reducing post-traumatic stress disorder symptoms; medications were not effective for mental comorbidities. Eight qualitative studies were included. Interventions were more acceptable if service users could identify benefits and if they were delivered in ways that accommodated their personal and social needs. Limitations: Assessments about long-term effectiveness of interventions were not possible. Studies that included outcomes related to comorbid psychiatric states, such as borderline personality disorder, and populations from prisons and humanitarian crises were under-represented. Conclusions: Evidence-based psychological interventions are effective and acceptable post treatment for reducing post-traumatic stress disorder symptoms and depression and anxiety in people with complex trauma. These interventions were less effective in veterans and had less of an impact on symptoms associated with complex post-traumatic stress disorder. Future work: Definitive trials of phase-based versus non-phase-based interventions with long-term follow-up for post-traumatic stress disorder and associated mental comorbidities. Study registration: This study is registered as PROSPERO CRD42017055523. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 43. See the NIHR Journals Library website for further project information

Psychological and pharmacological interventions for post-traumatic stress disorder and comorbid mental health problems following complex traumatic events: systematic review and component network meta-analysis

Background: Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at not only at risk of post-traumatic stress disorder (PTSD) but also other mental health comorbidities. While evidence-based psychological and pharmacological treatments are effective for single event PTSD it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events.Methods and Findings: We searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised and non-randomised controlled trials of psychological and pharmacological treatments for PTSD symptoms n people exposed to complex traumatic events, published up to 25th October 2019. We adopted a non-diagnostic approach and included studies of adults who have experienced complex trauma. Complex trauma sub-groups were: veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs for a total of 6158 participants were included in meta-analyses across the primary and secondary outcomes; 19 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ±9.3 years, and 42% were male. Nine non-randomised controlled trials were included. The mean age of participants in the non-randomised controlled trials was 40.6 ±9.4 years, and 47% were male. The average length of follow-up across all included studies at post-treatment for the primary outcome was 11.5 weeks. The pair-wise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k=46; n=3389; standardised mean difference, SMD=-0.82, 95% CI: -1.02 to -0.63) and active control (k-9; n=662; SMD=-0.35, 95% CI: -0.56 to -0.14) at post-treatment, and also compared with inactive control at 6-month follow-up (k=10; n=738; SMD=-0.45, 95% CI: -0.82 to -0.08). Psychological interventions reduced depressive symptoms (k=31; n=2075; SMD=-0.87, 95% CI: -1.11 to -0.63; I2=82.7%, p=0.000) and anxiety (k=15; n=1395; SMD=-1.03, 95% CI: -1.44 to -0.61; p=0.000) at post-treatment comparted with inactive control. Sleep quality was significantly improved at post-treatment by psychological interventions compared with inactive control (k=3; n=111; SMD=-1.00, 95% CI: -1.49 to-0.51; p=0.245). There were no significant differences between psychological interventions and inactive control group at post-treatment for quality of life (k=6; n=401; SMD=0.33, 95% CI: -0.01 to 0.66; p=0.021). Antipsychotic medicine (k=5; n=364; SMD=–0.45; –0.85 to –0.05; p=0.085) and Prazosin (k=3; n=110; SMD=-0.52; -1.03 to -0.02; p=0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower drop out, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma focused interventions across trauma sub-groups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multi-component interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k=17; n=1077; mean difference=-37.95, 95% CI: -60.84 to -15.16). Our use of a non-diagnostic inclusion strategy may have over-looked certain complex trauma populations with severe and enduring mental comorbidities. Additionally, the relative contribution of skills-based intervention components were not feasibly evaluated in the network meta-analysis.Conclusions: In this systematic review and meta-analysis we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multi-component interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority

Support for adults with autism spectrum disorder without intellectual impairment : Systematic review

Adults with autism spectrum disorder without intellectual impairment may benefit from a range of support services. This article presents the results of a systematic review assessing the effectiveness of supportive interventions for adults with autism spectrum disorder without intellectual impairment. A total of 32 studies were included; most focused on younger male participants. Although evidence was lacking for most types of intervention, employment programmes and social skills training were found to be effective for more proximal outcomes such as social skills. Evidence that any intervention improves mental health or well-being was very limited. Most interventions focused on mitigating specific deficits, rather than on providing broader support. Further research is needed on the effectiveness of supportive interventions such as advocacy and mentoring

Digital interventions in mental health : evidence syntheses and economic modelling

BACKGROUND: Economic evaluations provide evidence on whether or not digital interventions offer value for money, based on their costs and outcomes relative to the costs and outcomes of alternatives. OBJECTIVES: (1) Evaluate and summarise published economic studies about digital interventions across different technologies, therapies, comparators and mental health conditions; (2) synthesise clinical evidence about digital interventions for an exemplar mental health condition; (3) construct an economic model for the same exemplar mental health condition using the previously synthesised clinical evidence; and (4) consult with stakeholders about how they understand and assess the value of digital interventions. METHODS: We completed four work packages: (1) a systematic review and quality assessment of economic studies about digital interventions; (2) a systematic review and network meta-analysis of randomised controlled trials on digital interventions for generalised anxiety disorder; (3) an economic model and value-of-information analysis on digital interventions for generalised anxiety disorder; and (4) a series of knowledge exchange face-to-face and digital seminars with stakeholders. RESULTS: In work package 1, we reviewed 76 economic evaluations: 11 economic models and 65 within-trial analyses. Although the results of the studies are not directly comparable because they used different methods, the overall picture suggests that digital interventions are likely to be cost-effective, compared with no intervention and non-therapeutic controls, whereas the value of digital interventions compared with face-to-face therapy or printed manuals is unclear. In work package 2, we carried out two network meta-analyses of 20 randomised controlled trials of digital interventions for generalised anxiety disorder with a total of 2350 participants. The results were used to inform our economic model, but when considered on their own they were inconclusive because of the very wide confidence intervals. In work package 3, our decision-analytic model found that digital interventions for generalised anxiety disorder were associated with lower net monetary benefit than medication and face-to-face therapy, but greater net monetary benefit than non-therapeutic controls and no intervention. Value for money was driven by clinical outcomes rather than by intervention costs, and a value-of-information analysis suggested that uncertainty in the treatment effect had the greatest value (£12.9B). In work package 4, stakeholders identified several areas of benefits and costs of digital interventions that are important to them, including safety, sustainability and reducing waiting times. Four factors may influence their decisions to use digital interventions, other than costs and outcomes: increasing patient choice, reaching underserved populations, enabling continuous care and accepting the 'inevitability of going digital'. LIMITATIONS: There was substantial uncertainty around effect estimates of digital interventions compared with alternatives. This uncertainty was driven by the small number of studies informing most comparisons, the small samples in some of these studies and the studies' high risk of bias. CONCLUSIONS: Digital interventions may offer good value for money as an alternative to 'doing nothing' or 'doing something non-therapeutic' (e.g. monitoring or having a general discussion), but their added value compared with medication, face-to-face therapy and printed manuals is uncertain. Clinical outcomes rather than intervention costs drive 'value for money'. FUTURE WORK: There is a need to develop digital interventions that are more effective, rather than just cheaper, than their alternatives. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018105837. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 1. See the NIHR Journals Library website for further project information

AUT698939_Lay_Abstract – Supplemental material for Support for adults with autism spectrum disorder without intellectual impairment: Systematic review

<p> Supplemental material, AUT698939_Lay_Abstract for Support for adults with autism spectrum disorder without intellectual impairment: Systematic review by Theo Lorenc, Mark Rodgers, David Marshall, Hollie Melton, Rebecca Rees, Kath Wright and Amanda Sowden in Autism </p