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Background This work was undertaken to inform a National Institute for Health and Care Excellence guideline on the initial assessment of adults with suspected acute respiratory infection. Objective To undertake a rapid evidence synthesis of systematic reviews and cost-effectiveness studies of signs, symptoms and early warning scores for the initial assessment of adults with suspected acute respiratory infection. Methods MEDLINE, EMBASE and Cochrane Database of Systematic Reviews were searched for systematic reviews and MEDLINE, EMBASE, EconLit and National Health Service Economic Evaluation Database were searched for cost-effectiveness studies in May 2023. References of relevant studies were checked. Clinical outcomes of interest included escalation of care, antibiotic/antiviral use, time to resolution of symptoms, mortality and health-related quality of life. Risk of bias was assessed using the Risk of Bias in Systematic Reviews tool or the National Institute for Health and Care Excellence economic evaluations checklist. Results were summarised using narrative synthesis. Results Nine systematic reviews and one cost-effectiveness study met eligibility criteria. Seven reviews assessed several early warning scores for patients with community- acquired pneumonia, one assessed early warning scores for nursing home-acquired pneumonia and one assessed individual signs/symptoms and the Centor score for patients with sore throat symptoms; all in face-to-face settings. Two good-quality reviews concluded that further research is needed to validate the CRB-65 in primary care/community settings. One also concluded that further research is needed on the Pneumonia Severity Index in community settings; however, the Pneumonia Severity Index requires data from tests not routinely conducted in community settings. One good-quality review concluded that National Early Warning Score appears to be useful in an emergency department/acute medical setting. One review (unclear quality) concluded that the Pneumonia Severity Index and CURB-65 appear useful in an emergency department setting. Two poor-quality reviews concluded that early warning scores can support clinical judgement and one poor-quality review found numerous problems with using early warning scores in a nursing home setting. A good-quality review concluded that individual signs and symptoms have a modest ability to diagnose streptococcal pharyngitis, and that the Centor score can enhance appropriate prescribing of antibiotics. The cost-effectiveness study assessed clinical scores and rapid antigen detection tests for sore throat, compared to delayed antibiotic prescribing. The study concluded that the clinical score is a cost-effective approach when compared to delayed prescribing and rapid antigen testing. Conclusions Several early warning scores have been evaluated in adults with suspected acute respiratory infection, mainly the CRB-65, CURB-65 and Pneumonia Severity Index in patients with community-acquired pneumonia. The evidence was insufficient to determine what triage strategies avoid serious illness. Some early warning scores (CURB-65, Pneumonia Severity Index and National Early Warning Score) appear to be useful in an emergency department/acute medical setting; however, further research is required to validate the CRB-65 and Pneumonia Severity Index in primary care/community settings. The economic evidence indicated that clinical scores may be a cost-effective approach to triage patients compared with delayed prescribing. Future work and limitations Only systematic reviews were eligible for inclusion in the synthesis of clinical evidence. There was a great deal of overlap in the primary studies included in the reviews, many of which had significant limitations. No studies were undertaken in remote settings (e.g. NHS 111). Only one cost-effectiveness study was identified, with limited applicability to the review question. Funding This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR159945. Plain language summary Acute respiratory infections, such as cold and flu, are common and can be caused by viruses or bacteria. People with symptoms of acute respiratory infection often go to their general practitioner, who may advise them to stay at home (with or without antibiotics or antivirals) or might refer them to hospital if the infection is serious. Doctors assess the patient’s symptoms or may use a tool called an ‘early warning score’ to judge whether the infection is serious. A systematic review is a research method where all relevant studies assessing a specific question are found and summarised. We aimed to summarise all systematic reviews and cost-effectiveness studies that assessed signs, symptoms and ‘early warning scores’ in adults with suspected acute respiratory infections in the community (i.e. not hospitalised patients). We found nine systematic reviews and one cost-effectiveness study. Several different early warning scores for acute respiratory infection have been assessed in systematic reviews. Seven of the reviews assessed early warning scores in patients with community-acquired pneumonia. Good-quality reviews concluded that further research is needed to see how useful the ‘CRB-65’ and ‘Pneumonia Severity Index’ early warning scores are for assessing pneumonia severity in the community. Another good-quality review concluded that the ‘National Early Warning Score’ early warning score appears to be useful in an emergency department setting. A good-quality review found that individual symptoms are not very reliable for diagnosing pharyngitis caused by streptococcal bacteria in patients with sore throat; the review also found that the ‘Centor score’ can help doctors decide whether to prescribe antibiotics for pharyngitis. The cost-effectiveness study assessed clinical scores and rapid antigen detection tests (which test for substances that increase in our blood when we have certain infections) in patients with sore throat, and found that clinical scores may be cost-effective compared to delaying prescribing antibiotics.

Background: Attachment refers to an infant’s innate tendency to seek comfort from their caregiver. Research shows that attachment is important in promoting healthy social and emotional development. Many parenting interventions have been developed to improve attachment outcomes for children. However, numerous interventions used in routine practice have a limited evidence base, meaning that we cannot be sure if they are helpful or harmful. Objectives: This research aimed to conduct a large-scale survey to identify what interventions are being used in UK services to improve child attachment; conduct a systematic review to evaluate the evidence for parenting attachment interventions; and develop recommendations for future research and practice. Design and methods: We worked closely with our Expert Reference Group to plan a large-scale survey focused on relevant UK services. We then conducted two systematic reviews. One searched for all randomised controlled trial evidence for any attachment parenting intervention. The second searched for all research for the top 10 routinely used interventions identified from the survey. Results: The survey collected 625 responses covering 734 UK services. The results identified the 10 most commonly used interventions. The responses showed a limited use of validated measures and a wide variety of definitions of attachment. For the first review, seven studies were included from 2516 identified records. These were combined with results from previous reviews conducted by the team. Meta-analyses showed that, overall, parenting interventions are effective in reducing disorganised attachment (pooled odds ratio 0.54, 95% confidence interval 0.39 to 0.77) and increasing secure attachment (pooled odds ratio 1.85, 95% confidence interval 1.36 to 2.52). The second review searched the literature for the top 10 routinely used interventions identified by the survey; 61 studies were included from 1198 identified records. The results showed that many of the most commonly used interventions in UK services have a weak evidence base and those with the strongest evidence base are not as widely used. Conclusions: There is a need for better links between research and practice to ensure that interventions offered to families are safe and effective. Possible reasons for the disparity include the cost and accessibility of training. There is also a need for improved understanding by professionals regarding the meaning of attachment. Limitations: Although the survey had good geographical spread, most respondents were based in England. For review 2 we were unable to access a large number of papers; however, we conducted extensive reference checking to account for this. Future work: There is a need for robust research to test the efficacy of routinely used attachment interventions. Research could also explore why routinely used interventions are not consistently subject to thorough evaluation; how to embed dissemination, cost-effectiveness, fidelity and sustainability into research; and how to keep clinical practice up to date with research developments. Study registration: This study is registered as PROSPERO CRD42019137362. 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. 27, No. 2. See the NIHR Journals Library website for further project information.

Background: People with severe mental illness die 15–20 years earlier than the general population. Reasons why include that people with severe mental illness are more likely to smoke and be physically inactive as a result of social inequalities. Objectives: (1) Evaluate the clinical effectiveness of multiple risk behaviour interventions on behaviour change (e.g. smoking abstinence), and outcomes affected by behaviours (e.g. weight loss). (2) Compare the clinical effectiveness of interventions targeting multiple and single risk behaviours. (3) Examine the factors affecting outcomes (e.g. intervention content). (4) Assess the factors affecting experiences of interventions (e.g. barriers and facilitators). Data sources: The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE™ (Elsevier, Amsterdam, the Netherlands), MEDLINE, PsycInfo® (American Psychological Association, Washington, DC, USA) and Science Citation Index (Clarivate Analytics, Philadelphia, PA, USA) were searched from inception to October 2018, and an updated search was conducted in March 2020. An Applied Social Sciences Index and Abstracts (ASSIA) search and an updated Cochrane Central Register of Controlled Trials search were undertaken in September 2020. Study selection: Randomised controlled trials targeting single or multiple health risk behaviours among people with severe mental illness were included. Qualitative evidence on factors affecting the effectiveness of risk behaviour interventions was included. Study appraisal: Network meta-analyses were conducted to compare the effectiveness of multiple and single risk behaviour interventions. The mean differences were estimated for continuous outcomes; if this was not possible, standardised mean differences were calculated. Thematic syntheses of qualitative studies were conducted. Results: A total of 101 studies (67 randomised controlled trials and 34 qualitative studies) were included. Most outcomes were smoking abstinence, weight and body mass index. Just over half of studies were rated as having a high overall risk of bias. Trials focusing on smoking alone led to greater abstinence than targeting smoking and other behaviours. However, heterogeneity means that other explanations cannot be ruled out. For weight loss and body mass index, single risk behaviour (e.g. physical activity alone) and multiple risk behaviour (e.g. diet and physical activity) interventions had positive but modest benefits. For example, any risk behaviour intervention led to a 2 kg greater weight loss (–2.10 kg, 95% credible interval –3.14 to –1.06 kg) and approximately half a point (i.e. 0.5 kg/m2) greater body mass index reduction (–0.49 kg/m2, 95% credible interval –0.97 to –0.01 kg/m2) than treatment as usual. There were potential synergies for targeting multiple health behaviours for reduction in systolic and diastolic blood pressure. No evidence was found of a deterioration in mental health for people with severe mental illness engaging in interventions to reduce health risk behaviours. Qualitative studies found that people with severe mental illness favoured interventions promoting physical and mental health together, and that took their condition into account. However, trials focused mainly on promoting physical health. Limitations: Most quantitative studies focused on weight and body mass index; few assessed behavioural outcomes. Qualitative studies often addressed different aims. Conclusions: Multiple and single risk behaviour interventions were associated with positive but modest benefits on most outcomes. Interventions seeking to promote physical health were not associated with deterioration in mental health. There was a lack of overlap between quantitative and qualitative studies. Future work: Further research is needed to investigate whether or not health behaviour changes are maintained long term; tailoring weight-loss interventions for people with severe mental illness; and in terms of methods, co-production and mixed-methods approaches in future trials. Study registration: This study is registered as PROSPERO CRD42018104724. Funding: This project was funded by the National Institute for Health Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 6. See the NIHR Journals Library website for further project information.

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.

Background: Schools in the UK increasingly have to respond to anxiety, depression and conduct disorder as key causes of morbidity in children and young people. Objective: The objective was to assess the comparative effectiveness of educational setting-based interventions for the prevention of anxiety, depression and conduct disorder in children and young people. Design: This study comprised a systematic review, a network meta-analysis and an economic evaluation. Data sources: The databases MEDLINE, EMBASE™ (Elsevier, Amsterdam, the Netherlands), PsycInfo® (American Psychological Association, Washington, DC, USA) and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to 4 April 2018, and the NHS Economic Evaluation Database (NHS EED) was searched on 22 May 2019 for economic evaluations. No language or date filters were applied. Main outcomes: The main outcomes were post-intervention self-reported anxiety, depression or conduct disorder symptoms. Review methods: Randomised/quasi-randomised trials of universal or targeted interventions for the prevention of anxiety, depression or conduct disorder in children and young people aged 4–18 years were included. Screening was conducted independently by two reviewers. Data extraction was conducted by one reviewer and checked by a second. Intervention- and component-level network meta-analyses were conducted in OpenBUGS. A review of the economic literature and a cost–consequence analysis were conducted. Results: A total of 142 studies were included in the review, and 109 contributed to the network meta-analysis. Of the 109 studies, 57 were rated as having an unclear risk of bias for random sequence generation and allocation concealment. Heterogeneity was moderate. In universal secondary school settings, mindfulness/relaxation interventions [standardised mean difference (SMD) –0.65, 95% credible interval (CrI) –1.14 to –0.19] and cognitive–behavioural interventions (SMD –0.15, 95% CrI –0.34 to 0.04) may be effective for anxiety. Cognitive–behavioural interventions incorporating a psychoeducation component may be effective (SMD –0.30, 95% CrI –0.59 to –0.01) at preventing anxiety immediately post intervention. There was evidence that exercise was effective in preventing anxiety in targeted secondary school settings (SMD –0.47, 95% CrI –0.86 to –0.09). There was weak evidence that cognitive–behavioural interventions may prevent anxiety in universal (SMD –0.07, 95% CrI –0.23 to 0.05) and targeted (SMD –0.38, 95% CrI –0.84 to 0.07) primary school settings. There was weak evidence that cognitive–behavioural (SMD –0.04, 95% CrI –0.16 to 0.07) and cognitive–behavioural + interpersonal therapy (SMD –0.18, 95% CrI –0.46 to 0.08) may be effective in preventing depression in universal secondary school settings. Third-wave (SMD –0.35, 95% CrI –0.70 to 0.00) and cognitive–behavioural interventions (SMD –0.11, 95% CrI –0.28 to 0.05) incorporating a psychoeducation component may be effective at preventing depression immediately post intervention. There was no evidence of intervention effectiveness in targeted secondary, targeted primary or universal primary school settings post intervention. The results for university settings were unreliable because of inconsistency in the network meta-analysis. A narrative summary was reported for five conduct disorder prevention studies, all in primary school settings. None reported the primary outcome at the primary post-intervention time point. The economic evidence review reported heterogeneous findings from six studies. Taking the perspective of a single school budget and based on cognitive–behavioural therapy intervention costs in universal secondary school settings, the cost–consequence analysis estimated an intervention cost of £43 per student. Limitations: The emphasis on disorder-specific prevention excluded broader mental health interventions and restricted the number of eligible conduct disorder prevention studies. Restricting the study to interventions delivered in the educational setting may have limited the number of eligible university-level interventions. Conclusions: There was weak evidence of the effectiveness of school-based, disorder-specific prevention interventions, although effects were modest and the evidence not robust. Cognitive–behavioural therapy-based interventions may be more effective if they include a psychoeducation component. Future work: Future trials for prevention of anxiety and depression should evaluate cognitive–behavioural interventions with and without a psychoeducation component, and include mindfulness/relaxation or exercise comparators, with sufficient follow-up. Cost implications must be adequately measured. Study registration: This study is registered as PROSPERO CRD42016048184. Funding: This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research; Vol. 9, No. 8. See the NIHR Journals Library website for further project information.

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 ≥ 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.

Background: Despite a growing number of prescriptions for antidepressants (over 70 million in 2018), there is uncertainty about when people with depression might benefit from antidepressant medication and concern that antidepressants are prescribed unnecessarily. Objectives: The main objective of the PANDA (What are the indications for Prescribing ANtiDepressAnts that will lead to a clinical benefit?) research programme was to provide more guidance about when antidepressants are likely to benefit people with depression. We aimed to estimate the minimal clinically important difference for commonly used self-administered scales for depression and anxiety, and to understand more about how patients respond to such assessments. We carried out an observational study of patients with depressive symptoms and a placebo-controlled randomised controlled trial of sertraline versus placebo to estimate the treatment effect in UK primary care. The hypothesis was that the severity and duration of symptoms were related to treatment response. Design: The programme consisted of three phases. The first phase relied on the secondary analysis of existing data extracted from published trials. The second phase was the PANDA cohort study of patients with depressive symptoms who presented to primary care and were followed up 2, 4 and 6 weeks after a baseline assessment. Both quantitative and qualitative methods were used in the analysis. The third phase was a multicentre randomised placebo-controlled double-blind trial of sertraline versus placebo in patients presenting to primary care with depressive symptoms. Setting: UK primary care in Bristol, London, Liverpool and York. Participants: Patients aged 18–74 years who were experiencing depressive symptoms in primary care. Eligibility for the PANDA randomised controlled trial included that there was uncertainty about the benefits about treatment with an antidepressant. Interventions: In the PANDA randomised controlled trial, patients were individually randomised to 100 mg daily of sertraline or an identical placebo. The PANDA cohort study was an observational study. Main outcome measures: Depressive symptoms measured using the Patient Health Questionnaire were the primary outcome for the randomised controlled trial. Other outcomes included anxiety symptoms using the Generalised Anxiety Disorder-7; depressive symptoms using the Beck Depression Inventory, version 2; health-related quality of life; self-reported improvement; and cost-effectiveness. Results: The secondary analysis of existing randomised controlled trials [GENetic and clinical Predictors Of treatment response in Depression (GenPod), TREAting Depression with physical activity (TREAD) and Clinical effectiveness and cost-effectiveness of cognitive Behavioural Therapy as an adjunct to pharmacotherapy for treatment-resistant depression in primary care (CoBalT)] found evidence that the minimal clinically important difference increased as the initial severity of depressive symptoms rose. Our estimates of minimal clinically important difference were a 17% and 18% reduction in Beck Depression Inventory scores for GenPod and TREAD, respectively. In CoBalT, a 32% reduction corresponded to the minimal clinically important difference but the participants in this study had depression that had not responded to antidepressants. In the PANDA study cohort, and from our analyses in existing data, we found that the minimal clinically important difference varies considerably with the initial severity of depressive and anxiety symptoms. Expressing the minimal clinically important difference as a percentage reduction reduces this variation at higher scores, but at low scores the percentage reduction increased substantially. The results from the qualitative studies pointed out many limitations of the Patient Health Questionnaire-9 items in assessing change and recovery from depression. In the PANDA randomised controlled trial, there was no evidence that sertraline resulted in a reduction in depressive symptoms within 6 weeks of randomisation, but there was some evidence of a reduction by 12 weeks. However, sertraline led to a reduction in anxiety symptoms, an improvement of mental health-related quality of life and an increased likelihood of reporting improvement. The mean Patient Health Questionnaire-9 items score at 6 weeks was 7.98 (standard deviation 5.63) in the sertraline group and 8.76 (standard deviation 5.86) in the placebo group (5% relative reduction, 95% confidence interval –7% to 15%; p = 0.41). Of the secondary outcomes, there was strong evidence that sertraline reduced anxiety symptoms (Generalised Anxiety Disorder-7 score reduced by 17% (95% confidence interval 9% to 25%; p = 0.00005). Sertraline had a high probability (> 90%) of being cost-effective at 12 weeks. The PANDA randomised controlled trial found no evidence that treatment response or cost-effectiveness was related to severity or duration of depressive symptoms. The minimal clinically important difference estimates suggested that sertraline’s effect on anxiety, but not on depression, was likely to be clinically important. Limitations: The results from the randomised controlled trial and the estimates of minimal clinically important difference were not sufficiently precise to provide specific clinical guidance for individuals. We had low power in testing whether or not initial severity and duration of depressive symptoms are related to treatment response. Conclusions: The results of the trial support the use of sertraline and probably other selective serotonin reuptake inhibitors because of their action in reducing anxiety symptoms and the likelihood of longer-term benefit on depressive symptoms. Sertraline could be prescribed for anxiety symptoms that commonly occur with depression and many patients will experience a clinical benefit. The Patient Health Questionnaire-9 items and similar self-administered scales should not be used on their own to assess clinical outcome, but should be supplemented with further clinical assessment. Future work: We need to examine the longer-term effects of antidepressant treatment. We need more precise estimates of the treatment effects and minimal clinically important difference at different severities to provide more specific guidance for individuals. However, the methods we have developed provide an approach towards providing such detailed guidance. Trial registration: Current Controlled Trials ISRCTN84544741 and EudraCT number 2013-003440-22. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 10. See the NIHR Journals Library website for further project information.

Background: Child maltreatment is a substantial social problem that affects large numbers of children and young people in the UK, resulting in a range of significant short- and long-term psychosocial problems. Objectives: To synthesise evidence of the effectiveness, cost-effectiveness and acceptability of interventions addressing the adverse consequences of child maltreatment. Study design: For effectiveness, we included any controlled study. Other study designs were considered for economic decision modelling. For acceptability, we included any study that asked participants for their views. Participants: Children and young people up to 24 years 11 months, who had experienced maltreatment before the age of 17 years 11 months. Interventions: Any psychosocial intervention provided in any setting aiming to address the consequences of maltreatment. Main outcome measures: Psychological distress [particularly post-traumatic stress disorder (PTSD), depression and anxiety, and self-harm], behaviour, social functioning, quality of life and acceptability. Methods: Young Persons and Professional Advisory Groups guided the project, which was conducted in accordance with Cochrane Collaboration and NHS Centre for Reviews and Dissemination guidance. Departures from the published protocol were recorded and explained. Meta-analyses and cost-effectiveness analyses of available data were undertaken where possible. Results: We identified 198 effectiveness studies (including 62 randomised trials); six economic evaluations (five using trial data and one decision-analytic model); and 73 studies investigating treatment acceptability. Pooled data on cognitive–behavioural therapy (CBT) for sexual abuse suggested post-treatment reductions in PTSD [standardised mean difference (SMD) –0.44 (95% CI –4.43 to –1.53)], depression [mean difference –2.83 (95% CI –4.53 to –1.13)] and anxiety [SMD –0.23 (95% CI –0.03 to –0.42)]. No differences were observed for post-treatment sexualised behaviour, externalising behaviour, behaviour management skills of parents, or parental support to the child. Findings from attachment-focused interventions suggested improvements in secure attachment [odds ratio 0.14 (95% CI 0.03 to 0.70)] and reductions in disorganised behaviour [SMD 0.23 (95% CI 0.13 to 0.42)], but no differences in avoidant attachment or externalising behaviour. Few studies addressed the role of caregivers, or the impact of the therapist–child relationship. Economic evaluations suffered methodological limitations and provided conflicting results. As a result, decision-analytic modelling was not possible, but cost-effectiveness analysis using effectiveness data from meta-analyses was undertaken for the most promising intervention: CBT for sexual abuse. Analyses of the cost-effectiveness of CBT were limited by the lack of cost data beyond the cost of CBT itself. Conclusions: It is not possible to draw firm conclusions about which interventions are effective for children with different maltreatment profiles, which are of no benefit or are harmful, and which factors encourage people to seek therapy, accept the offer of therapy and actively engage with therapy. Little is known about the cost-effectiveness of alternative interventions. Limitations: Studies were largely conducted outside the UK. The heterogeneity of outcomes and measures seriously impacted on the ability to conduct meta-analyses. Future work: Studies are needed that assess the effectiveness of interventions within a UK context, which address the wider effects of maltreatment, as well as specific clinical outcomes. Study registration: This study is registered as PROSPERO CRD42013003889. Funding: The National Institute for Health Research Health Technology Assessment programme.

Background: Obsessive–compulsive disorder (OCD) is a relatively common and disabling condition. Objectives: To determine the clinical effectiveness, acceptability and cost-effectiveness of pharmacological and psychological interventions for the treatment of OCD in children, adolescents and adults. Data sources: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Trials Registers, which includes trials from routine searches of all the major databases. Searches were conducted from inception to 31 December 2014. Review methods: We undertook a systematic review and network meta-analysis (NMA) of the clinical effectiveness and acceptability of available treatments. Outcomes for effectiveness included mean differences in the total scores of the Yale–Brown Obsessive–Compulsive Scale or its children’s version and total dropouts for acceptability. For the cost-effectiveness analysis, we developed a probabilistic model informed by the results of the NMA. All analyses were performed using OpenBUGS version 3.2.3 (members of OpenBUGS Project Management Group; see www.openbugs.net). Results: We included 86 randomised controlled trials (RCTs) in our systematic review. In the NMA we included 71 RCTs (54 in adults and 17 in children and adolescents) for effectiveness and 71 for acceptability (53 in adults and 18 in children and adolescents), comprising 7643 and 7942 randomised patients available for analysis, respectively. In general, the studies were of medium quality. The results of the NMA showed that in adults all selective serotonin reuptake inhibitors (SSRIs) and clomipramine had greater effects than drug placebo. There were no differences between SSRIs, and a trend for clomipramine to be more effective did not reach statistical significance. All active psychological therapies had greater effects than drug placebo. Behavioural therapy (BT) and cognitive therapy (CT) had greater effects than psychological placebo, but cognitive–behavioural therapy (CBT) did not. BT and CT, but not CBT, had greater effects than medications, but there are considerable uncertainty and methodological limitations that should be taken into account. In children and adolescents, CBT and BT had greater effects than drug placebo, but differences compared with psychological placebo did not reach statistical significance. SSRIs as a class showed a trend for superiority over drug placebo, but the difference did not reach statistical significance. However, the superiority of some individual drugs (fluoxetine, sertraline) was marginally statistically significant. Regarding acceptability, all interventions except clomipramine had good tolerability. In adults, CT and BT had the highest probability of being most cost-effective at conventional National Institute for Health and Care Excellence thresholds. In children and adolescents, CBT or CBT combined with a SSRI were more likely to be cost-effective. The results are uncertain and sensitive to assumptions about treatment effect and the exclusion of trials at high risk of bias. Limitations: The majority of psychological trials included patients who were taking medications. There were few studies in children and adolescents. Conclusions: In adults, psychological interventions, clomipramine, SSRIs or combinations of these are all effective, whereas in children and adolescents, psychological interventions, either as monotherapy or combined with specific SSRIs, were more likely to be effective. Future RCTs should improve their design, in particular for psychotherapy or combined interventions. Study registration: The study is registered as PROSPERO CRD42012002441. Funding details: The National Institute for Health Research Health Technology Assessment programme.

Background: Serious parental mental illness poses a challenge to quality of life (QoL) in a substantial number of children and adolescents. Improving the lives of these children is a political and public health concern. Objectives: To conduct an evidence synthesis of the clinical effectiveness, cost-effectiveness and acceptability of community-based interventions for improving QoL in children of parents with serious mental illness (SMI). Data sources: Nineteen health, allied health and educational databases, searched from database inception to May 2012, and supplemented with hand searches, reference checking, searches of grey literature, dissertations, ongoing research registers, forward citation tracking and key author contact. Review methods: Inclusion criteria required ≥ 50% of parents to have SMI or severe depression confirmed by clinical diagnosis or baseline symptoms. Children were ≤ 18 years of age. Community-based interventions included any non-residential psychological/psychosocial intervention involving parents or children for the purposes of improving health or well-being. Intervention comparators were not predefined and primary outcomes were validated measures of children’s QoL and emotional health. Secondary outcomes were derived from UK policy and stakeholder consultation. Data were extracted independently by two reviewers and the study quality was assessed via Cochrane criteria for randomised/non-randomised designs, Critical Appraisal Skills Programme (CASP) qualitative criteria or a standard checklist for economic evaluations. Separate syntheses were conducted for SMI and severe depression. Standardised effect size (ES) trials were pooled using random-effects modelling for which sufficient data were available. Economic data were summarised and acceptability data were synthesised via a textual narrative approach. Results: Three trials targeted mothers/the children of mothers with psychotic symptoms. Children were ≤ 12 years of age and no primary QoL or emotional health outcomes were reported. Insufficient secondary outcome data prevented pooling and no eligible economic evaluations were found. Twenty-six trials targeted parents/children of parents with severe depression; 18 recruited mothers of infants