A review and analysis of the components of potentially effective perinatal mental health interventions for infant development and mother-infant relationship outcomes.

Children of mothers with serious mental health difficulties are at increased risk of developing mental health difficulties themselves in their own lifetime. Specialist interventions delivered in perinatal mental health services offer an opportunity to support the infant's development and long-term mental health. This review aimed to systematically evaluate the shared elements of successful perinatal mental health interventions that underpin improved outcomes for infants whose mothers experience perinatal mental health difficulties. Nine electronic databases were searched comprehensively for relevant controlled studies of perinatal mental health interventions, and a narrative synthesis undertaken to assess whether statistically significant benefits were noted. Sixteen studies, trialing 19 interventions, were analyzed using a narrative approach and grouped according to reported effectiveness. Eight interventions demonstrated significant improvements in infant outcomes and/or mother-infant relationship outcomes and were used to inform the analysis of the included interventions' components. While the interventions identified were diverse, there were common components which potentially underpin successful interventions for infants whose mothers are experiencing mental health difficulties, including: facilitation of positive Mother×Infant interactions; helping mothers to understand their infant's perspective or inner world; and the use of video feedback.

Sulfide Oxidation by 2,6-Bis[hydroxyl(methyl)amino]-4-morpholino-1,3,5-triazinatodioxomolybdenum(VI): Mechanistic Implications with DFT Calculations for a New Class of Molybdenum(VI) Complex.

Sulfide oxidation is accomplished by a new class of dioxomolybdenum(VI) catalyst (1) that uses the tridentate 2,6-bis[hydroxyl(methyl)amino]-4-morpholino-1,3,5-triazine ligand to form a five-coordinate molybdenum(VI) center. Resonance Raman spectra show that the dioxo groups on the Mo(VI) oxygens readily exchange with water in an acetonitrile media that allows 18O labeling of catalyst 1. The model oxidation reaction was the conversion of thioanisole (2) to the corresponding sulfoxide with 4% of 1 using an equimolar amount of H2O2 in MeCN-d3. Oxygen-18 labeling experiments with either 18O-labeled 1 or 18O-labeled H2O2 are consistent with a sulfide oxygenation pathway that uses a η1-Mo(OOH) hydroxoperoxyl species (3). The hypothesized intermediate 3 is initially formed in a proton transfer reaction between 1 and H2O2. Oxidation is hypothesized via nucleophilic attack of the sulfide on 3 that is supported from a Hammett linear free-energy relationship for para-derivatives of 2. A Hammett reactivity constant (ρ) of -1.2 ± 0.2 was obtained, which is consistent with other ρ values found in prior sulfide oxidation reactions by group 6 complexes. An Eyring plot of the 2 oxidation by 1 gives an Ea of 63.0 ± 5.2 kJ/mol, which is slightly higher than that of a similar oxidation of 2 by the molybdenum(VI) complex, oxodiperoxo (pyridine-2-carboxylato)molybdate(VI) bis(pyridine-2-carboxylic acid) monohydrate (5). Computational modeling with density functional theory (DFT) of the complete reaction profile gave enthalpy and entropy of activations (64 kJ/mol and -120 J/mol·K, respectively) within 1 standard deviation of the experimental values, further supporting the hypothesized mechanism.

An Unexpected Ireland-Claisen Rearrangement Cascade During the Synthesis of the Tricyclic Core of Curcusone C: Mechanistic Elucidation by Trial-and-Error and Automatic Artificial Force-Induced Reaction (AFIR) Computations.

In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence. Since the involvement of a thermally forbidden 1,3-shift seemed unlikely, theoretical studies involving two approaches, the "trial-and-error" testing of various conceivable mechanisms (Houk group) and an "automatic" approach using the Maeda-Morokuma AFIR method (Morokuma group) were applied to explore the mechanism. Eventually, both approaches converged on a cascade mechanism shown to have some partial literature precedent: Cope rearrangement/1,5-sigmatropic silyl shift/Claisen rearrangement/retro-Claisen rearrangement/1,5-sigmatropic silyl shift, comprising a quintet of five sequential thermally allowed pericyclic rearrangements.

A Unified Explanation for Chemoselectivity and Stereospecificity of Ni-Catalyzed Kumada and Cross-Electrophile Coupling Reactions of Benzylic Ethers: A Combined Computational and Experimental Study.

Ni-catalyzed C(sp3)-O bond activation provides a useful approach to synthesize enantioenriched products from readily available enantioenriched benzylic alcohol derivatives. The control of stereospecificity is key to the success of these transformations. To elucidate the reversed stereospecificity and chemoselectivity of Ni-catalyzed Kumada and cross-electrophile coupling reactions with benzylic ethers, a combined computational and experimental study is performed to reach a unified mechanistic understanding. Kumada coupling proceeds via a classic cross-coupling mechanism. Initial rate-determining oxidative addition occurs with stereoinversion of the benzylic stereogenic center. Subsequent transmetalation with the Grignard reagent and syn-reductive elimination produce the Kumada coupling product with overall stereoinversion at the benzylic position. The cross-electrophile coupling reaction initiates with the same benzylic C-O bond cleavage and transmetalation to form a common benzylnickel intermediate. However, the presence of the tethered alkyl chloride allows a facile intramolecular SN2 attack by the benzylnickel moiety. This step circumvents the competing Kumada coupling, leading to the excellent chemoselectivity of cross-electrophile coupling. These mechanisms account for the observed stereospecificity of the Kumada and cross-electrophile couplings, providing a rationale for double inversion of the benzylic stereogenic center in cross-electrophile coupling. The improved mechanistic understanding will enable design of stereoselective transformations involving Ni-catalyzed C(sp3)-O bond activation.

Public involvement in health outcomes research: lessons learnt from the development of the recovering quality of life (ReQoL) measures.

BACKGROUND: To provide a model for Public involvement (PI) in instrument development and other research based on lessons learnt in the co-production of a recently developed mental health patient reported outcome measure called Recovering Quality of Life (ReQoL). While service users contributed to the project as research participants, this paper focuses on the role of expert service users as research partners, hence referred to as expert service users or PI. METHODS: At every stage of the development, service users influenced the design, content and face validity of the measure, collaborating with other researchers, clinicians and stakeholders who were central to this research. Expert service users were integral to the Scientific Group which was the main decision-making body, and also provided advice through the Expert Service User Group. RESULTS: During the theme and item generation phase (stage 1) expert service users affirmed the appropriateness of the seven domains of the Patient Reported Outcome Measure (activity, hope, belonging and relationships, self-perception, wellbeing, autonomy, and physical health). Expert service users added an extra 58 items to the pool of 180 items and commented on the results from the face and content validity testing (stage 2) of a refined pool of 88. In the item reduction and scale generation phase (stage 3), expert service users contributed to discussions concerning the ordering and clustering of the themes and items and finalised the measures. Expert service users were also involved in the implementation and dissemination of ReQoL (stage 4). Expert service users contributed to the interpretation of findings, provided inputs at every stage of the project and were key decision-makers. The challenges include additional work to make the technical materials accessible, extra time to the project timescales, including time to achieve consensus from different opinions, sometimes strongly held, and extra costs. CONCLUSION: This study demonstrates a successful example of how PI can be embedded in research, namely in instrument development. The rewards of doing so cannot be emphasised enough but there are challenges, albeit surmountable ones. Researchers should anticipate and address those challenges during the planning stage of the project.

Recovering Quality of Life (ReQoL): a new generic self-reported outcome measure for use with people experiencing mental health difficulties.

BACKGROUND: Outcome measures for mental health services need to adopt a service-user recovery focus. Aims To develop and validate a 10- and 20-item self-report recovery-focused quality of life outcome measure named Recovering Quality of Life (ReQoL). METHOD: Qualitative methods for item development and initial testing, and quantitative methods for item reduction and scale construction were used. Data from >6500 service users were factor analysed and item response theory models employed to inform item selection. The measures were tested for reliability, validity and responsiveness. RESULTS: ReQoL-10 and ReQoL-20 contain positively and negatively worded items covering seven themes: activity, hope, belonging and relationships, self-perception, well-being, autonomy, and physical health. Both versions achieved acceptable internal consistency, test-retest reliability (>0.85), known-group differences, convergence with related measures, and were responsive over time (standardised response mean (SRM) > 0.4). They performed marginally better than the Short Warwick-Edinburgh Mental Well-being Scale and markedly better than the EQ-5D. CONCLUSIONS: Both versions are appropriate for measuring service-user recovery-focused quality of life outcomes. Declaration of interest M.B. and J.Co. were members of the research group that developed the Clinical Outcomes in Routine Evaluation (CORE) outcome measures.

The importance of content and face validity in instrument development: lessons learnt from service users when developing the Recovering Quality of Life measure (ReQoL).

PURPOSE: Service user involvement in instrument development is increasingly recognised as important, but is often not done and seldom reported. This has adverse implications for the content validity of a measure. The aim of this paper is to identify the types of items that service users felt were important to be included or excluded from a new Recovering Quality of Life measure for people with mental health difficulties. METHODS: Potential items were presented to service users in face-to-face structured individual interviews and focus groups. The items were primarily taken or adapted from current measures and covered themes identified from earlier qualitative work as being important to quality of life. Content and thematic analysis was undertaken to identify the types of items which were either important or unacceptable to service users. RESULTS: We identified five key themes of the types of items that service users found acceptable or unacceptable; the items should be relevant and meaningful, unambiguous, easy to answer particularly when distressed, do not cause further upset, and be non-judgemental. Importantly, this was from the perspective of the service user. CONCLUSIONS: This research has underlined the importance of service users' views on the acceptability and validity of items for use in developing a new measure. Whether or not service users favoured an item was associated with their ability or intention to respond accurately and honestly to the item which will impact on the validity and sensitivity of the measure.

Mechanism and Origins of Ligand-Controlled Stereoselectivity of Ni-Catalyzed Suzuki-Miyaura Coupling with Benzylic Esters: A Computational Study.

Nickel catalysts have shown unique ligand control of stereoselectivity in the Suzuki-Miyaura cross-coupling of boronates with benzylic pivalates and derivatives involving C(sp3)-O cleavage. The SIMes ligand (1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) produces the stereochemically inverted C-C coupling product, while the tricyclohexylphosphine (PCy3) ligand delivers the retained stereochemistry. We have explored the mechanism and origins of the ligand-controlled stereoselectivity with density functional theory (DFT) calculations. The oxidative addition determines the stereoselectivity with two competing transition states, an SN2 back-side attack type transition state that inverts the benzylic stereogenic center and a concerted oxidative addition through a cyclic transition state, which provides stereoretention. The key difference between the two transition states is the substrate-nickel-ligand angle distortion; the ligand controls the selectivity by differentiating the ease of this angle distortion. For the PCy3 ligand, the nickel-ligand interaction involves mainly σ-donation, which does not require a significant energy penalty for the angle distortion. The facile angle distortion with PCy3 ligand allows the favorable cyclic oxidative addition transition state, leading to the stereoretention. For the SIMes ligand, the extra d-p back-donation from nickel to the coordinating carbene increases the rigidity of the nickel-ligand bond, and the corresponding angle distortion is more difficult. This makes the concerted cyclic oxidative addition unfavorable with SIMes ligand, and the back-side SN2-type oxidative addition delivers the stereoinversion.

Experimental and Computational Development of a Conformationally Flexible Template for the meta-C-H Functionalization of Benzoic Acids.

A conformationally flexible template for the meta-C-H olefination of benzoic acids was designed through both experimental and computational efforts. The newly designed template favors a silver-palladium heterodimer low barrier transition state, and demonstrates that it is feasible to lengthen templates so as to achieve meta-selectivity when the distance between the functional handle of the native substrate and target C-H bond decreases. Analysis of the ortho-, meta-, and para-C-H cleavage transition states determined that the new template conformation optimizes the interaction between the nitrile and palladium-silver dimer in the meta-transition state, enabling palladium to cleave meta-C-H bonds with moderate-to-good yields and generally high regioselectivity. Regioselectivity is governed exclusively by the template, and kinetic experiments reveal that there is a 4-fold increase in rate in the presence of monoprotected amino acid ligands. Using a Boltzmann distribution of all accessible C-H activation transition states, it is possible to computationally predict meta-selectivity in a number of investigated templates with reasonable accuracy. Structural and distortion energies reported may be used for the further development of templates for meta-C-H activation of hitherto unexplored arene substrates.

Z-Selective Cross-Metathesis and Homodimerization of 3E-1,3-Dienes: Reaction Optimization, Computational Analysis, and Synthetic Applications.

Olefin metathesis reactions with 3E-1,3-dienes using Z-selective cyclometalated ruthenium benzylidene catalysts are described. In particular, a procedure for employing 3E-1,3-dienes in Z-selective homodimerization and cross-metathesis with terminal alkenes is detailed. The reaction takes advantage of the pronounced chemoselectivity of a recently reported ruthenium-based catalyst containing a cyclometalated NHC ligand for terminal alkenes in the presence of internal E-alkenes. A wide array of commonly encountered functional groups can be tolerated, and only a small excess (1.5 equiv) of the diene coupling partner is required to achieve high yields of the desired internal E,Z-diene cross-metathesis product. Computational studies have been performed to elucidate the reaction mechanism. The computations are consistent with a diene-first pathway. The reaction can be used to quickly assemble structurally complex targets. The power of this cross-metathesis reaction is demonstrated by the concise syntheses of two insect pheromones.

The delivery of creative socially prescribed activities for people with serious mental health needs during lockdown: Learning about remote, digital and hybrid delivery.

BACKGROUND: Social prescribing interventions connect mental health service users to community resources, to support physical and mental wellbeing and promote recovery. COVID-19 restrictions impacted the delivery of socially prescribed activities, preventing face to face contact for long periods. AIMS: The aim of this study was to understand how Voluntary Community and Social Enterprise (VCSE) organisations working with a local NHS mental health Trust responded to the challenges of social distancing during the COVID-19 pandemic. This understanding will be used to make recommendations for future practice, post-lockdown. METHODS: Using a convergent mixed methods design, we surveyed VCSE providers of socially prescribed activities intended to be accessible and appropriate for people with severe mental health needs. Follow-up interviews explored further how they adapted during the first year of the pandemic, the challenges they faced, and how they sought to overcome them. The survey and interview data were analysed separately and then compared to identify convergent and divergent findings. RESULTS: Twenty VCSE representatives completed the survey which provided a snapshot of changes in levels of connection and numbers reached during lockdown. Of 20 survey respondents, 11 participated in follow-up interviews. Interviews revealed that lockdown necessitated rapid change and responsive adaptation; activities were limited by resource, funding, safeguarding and government restrictions; no single format suited all group members; connection was key; and impact was difficult to gauge. CONCLUSIONS: VCSE organisations commissioned to deliver creative socially prescribed activities during the pandemic rapidly adapted their offer to comply with government restrictions. Responsive changes were made, and new knowledge and skills were gained. Drawing on experiences during lockdown, VCSE organisations should develop bespoke knowledge, skills and practices to engage service users in future hybrid delivery of arts, sports, cultural and creative community activities, and to ensure that digital activities offer an equivalent degree of connection to face-to-face ones. Additionally, more effective methods of gaining feedback about patient experience of hybrid delivery is needed.

Factors within the clinical encounter that impact upon risk assessment within child and adolescent mental health services: a rapid realist synthesis.

Background: Risk assessment is a key process when a child or adolescent presents at risk for self-harm or suicide in a mental health crisis or emergency. Risk assessment by a healthcare professional should be included within a biopsychosocial assessment. However, the predictive value of risk-screening tools for self-harm and suicide in children and adolescents is consistently challenged. A review is needed to explore how best to undertake risk assessment and the appropriate role for tools/checklists within the assessment pathway. Aims: To map research relating to risk assessment for child and adolescent mental health and to identify features that relate to a successful risk assessment. Objectives: To review factors within the clinical encounter that impact upon risk assessments for self-harm and suicide in children and adolescents: i. to conduct a realist synthesis to understand mechanisms for risk assessment, why they occur and how they vary by context ii. to conduct a mapping review of primary studies/reviews to describe available tools of applicability to the UK. Data sources: Databases, including MEDLINE, PsycINFO®, EMBASE, CINAHL, HMIC, Science and Social Sciences Citation Index and the Cochrane Library, were searched (September 2021). Searches were also conducted for reports from websites. Review methods: A resource-constrained realist synthesis was conducted exploring factors that impact upon risk assessments for self-harm and suicide. This was accompanied by a mapping review of primary studies/reviews describing risk-assessment tools and approaches used in UK child and adolescent mental health. Following piloting, four reviewers screened retrieved records. Items were coded for the mapping and/or for inclusion in the realist synthesis. The review team examined the validity and limitations of risk-screening tools. In addition, the team identified structured approaches to risk assessment. Reporting of the realist synthesis followed RAMESES guidelines. Results: From 4084 unique citations, 249 papers were reviewed and 41 studies (49 tools) were included in the mapping review. Eight reviews were identified following full-text screening. Fifty-seven papers were identified for the realist review. Findings highlight 14 explanations (programme theories) for a successful risk assessment for self-harm and suicide. Forty-nine individual assessment tools/approaches were identified. Few tools were developed in the UK, specifically for children and adolescents. These lacked formal independent evaluation. No risk-screening tool is suitable for risk prediction; optimal approaches incorporate a relationship of trust, involvement of the family, where appropriate, and a patient-centred holistic approach. The objective of risk assessment should be elicitation of information to direct a risk formulation and care plan. Limitations: Many identified tools are well-established but lack scientific validity, particularly predictive validity, or clinical utility. Programme theories were generated rapidly from a survey of risk assessment. Conclusions: No single checklist/approach meets the needs of risk assessment for self-harm and suicide. A whole-system approach is required, informed by structured clinical judgement. Useful components include a holistic assessment within a climate of trust, facilitated by family involvement. Study registration: This study is registered as PROSPERO CRD42021276671. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR135079) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 1. See the NIHR Funding and Awards website for further award information.

When young people up to 18 years of age present to health services, having tried to poison themselves, take an overdose or injure themselves, a health professional needs to work out whether this is likely to happen again (risk assessment). Lists of questions or things to look for (risk screening) have proved unreliable. Thorough discussion with the child or teenager may be helpful but takes much time. How can a health professional best use time spent with a young person to prevent further harm and make sure that they get the treatment that they need? This review focuses on young persons who use health services in the UK. Included studies report how health professionals work out whether young people are likely to harm themselves; either how to handle the overall discussion or to use memory aids or checklists (known as tools) to help the discussion. Tools developed in the USA many years ago have not been tested well enough with UK populations. Recent approaches within the UK are used inconsistently. Young persons do not like how they are assessed. Health professionals may use methods that have not been shown to work or use tools differently from how they were designed. This review identified 14 ways to help a young person have valued discussions with a health professional. Health professionals should not simply 'tick boxes'; tools should help them gain a full picture, including input from other family members. Health professionals should create a trusted relationship where the young person feels respected and heard. Tools should not label someone 'at risk' but should support care that reduces the risk of further harm. Health professionals should gather good-quality information that includes asking about thoughts of suicide. Staff should be supported by training, guidance and feedback from experienced colleagues.

Synthesis of enantioenriched triarylmethanes by stereospecific cross-coupling reactions.

Coupling with inversion: Chiral diarylmethanol derivatives undergo a stereospecific nickel-catalyzed cross-coupling reaction with aryl Grignard reagents (see scheme). The reaction proceeds with inversion of configuration and high enantiospecificity. The method has been applied to the asymmetric synthesis of a triarylmethane-based anti-cancer compound.

Meeting sustainable development goals via robotics and autonomous systems.

Robotics and autonomous systems are reshaping the world, changing healthcare, food production and biodiversity management. While they will play a fundamental role in delivering the UN Sustainable Development Goals, associated opportunities and threats are yet to be considered systematically. We report on a horizon scan evaluating robotics and autonomous systems impact on all Sustainable Development Goals, involving 102 experts from around the world. Robotics and autonomous systems are likely to transform how the Sustainable Development Goals are achieved, through replacing and supporting human activities, fostering innovation, enhancing remote access and improving monitoring. Emerging threats relate to reinforcing inequalities, exacerbating environmental change, diverting resources from tried-and-tested solutions and reducing freedom and privacy through inadequate governance. Although predicting future impacts of robotics and autonomous systems on the Sustainable Development Goals is difficult, thoroughly examining technological developments early is essential to prevent unintended detrimental consequences. Additionally, robotics and autonomous systems should be considered explicitly when developing future iterations of the Sustainable Development Goals to avoid reversing progress or exacerbating inequalities.

Stereospecific nickel-catalyzed cross-coupling reactions of alkyl ethers: enantioselective synthesis of diarylethanes.

Secondary benzylic ethers undergo stereospecific substitution reactions with Grignard reagents in the presence of nickel catalysts. Reactions proceed with inversion of configuration and high stereochemical fidelity. This reaction allows for facile enantioselective synthesis of biologically active diarylethanes from readily available optically enriched carbinols.

Stereochemistry of transmetalation of alkylboranes in nickel-catalyzed alkyl-alkyl cross-coupling reactions.

Deuterium-labeled alkylborane reagents 2a and 2b were prepared and subjected to cross-coupling reactions in the presence of a nickel catalyst. NMR analysis of the products indicates that transmetalation from boron to nickel proceeds with retention of configuration. These results demonstrate that alkylnickel intermediates are configurationally stable under Suzuki cross-coupling conditions.

Integrating Qualitative and Quantitative Data in the Development of Outcome Measures: The Case of the Recovering Quality of Life (ReQoL) Measures in Mental Health Populations.

While it is important to treat symptoms, there is growing recognition that in order to help people with mental health problems lead meaningful and fulfilling lives, it is crucial to capture the impact of their conditions on wider aspects of their social lives. We constructed two versions of the Recovering Quality of Life (ReQoL) measure—ReQoL-10 and ReQoL-20—for use in routine settings and clinical trials from a larger pool of items by combining qualitative and quantitative evidence covering six domains. Qualitative evidence was gathered through interviews and focus groups with over 76 service users, clinicians, and a translatability assessment. Psychometric evidence generated from data from over 6200 service users was obtained from confirmatory factor models and item response theory analyses. In this paper we present an approach based on a traffic light pictorial format that was developed to present qualitative and quantitative evidence to a group of service users, clinicians, and researchers to help to make the final selection. This work provides a pragmatic yet rigorous approach to combining qualitative and quantitative evidence to ensure that ReQoL is psychometrically robust and has high relevance to service users and clinicians. This approach can be extended to the development of patient reported outcome measures in general.

Mechanistic analysis of an asymmetric palladium-catalyzed conjugate addition of arylboronic acids to ß-substituted cyclic enones.

An asymmetric palladium-catalyzed conjugate addition reaction of arylboronic acids to enone substrates was investigated mechanistically. Desorption electrospray ionization coupled to mass spectrometry was used to identify intermediates of the catalytic cycle and delineate differences in substrate reactivity. Our findings provide evidence for the catalytic cycle proceeding through formation of an arylpalladium(II) cation, subsequent formation of an arylpalladium-enone complex, and, ultimately, formation of the new C-C bond. Reaction monitoring in both positive and negative ion modes revealed that 4-iodophenylboronic acid formed a relatively stable trimeric species under the reaction conditions.

Systematic review and economic modelling of the clinical effectiveness and cost-effectiveness of art therapy among people with non-psychotic mental health disorders.

BACKGROUND: Mental health problems account for almost half of all ill health in people under 65 years. The majority are non-psychotic (e.g. depression, anxiety and phobias). For some people, art therapy may provide more profound and long-lasting healing than more standard forms of treatment, perhaps because it can provide an alternative means of expression and release from trauma. As yet, no formal evaluation of art therapy for non-psychotic mental health disorders has been conducted. AIM: This review aimed to evaluate evidence for the clinical effectiveness and cost-effectiveness of art therapy for non-psychotic mental health disorders. METHODS: Comprehensive literature searches for studies examining art therapy in populations with non-psychotic mental health disorders were performed in major health-related and social science bibliographic databases including MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Allied and Complementary Medicine Database (AMED) and Applied Social Sciences Index and Abstracts (ASSIA) from inception up to May 2013. A quantitative systematic review of clinical effectiveness, a qualitative review to explore the acceptability, relative benefits and potential harms, and a cost-utility analysis of studies evaluating cost-effectiveness of art therapy were conducted. RESULTS: In the quantitative review, 15 randomised controlled trials (RCTs) were included (n = 777). Meta-analysis was not possible because of clinical heterogeneity and insufficient comparable data on outcome measures across studies. A narrative synthesis reports that art therapy was associated with significant positive changes relative to the control group in mental health symptoms in 10 out of the 15 studies. The control groups varied between studies but included wait-list/no treatment, attention placebo controls and psychological therapy comparators. Four studies reported improvement from baseline but no significant difference between groups. One study reported that outcomes were more favourable in the control group. The quality of included RCTs was generally low. In the qualitative review, 12 cohort studies were included (n = 188 service users; n = 16 service providers). Themes relating to benefits of art therapy for service users included the relationship with the therapist, personal achievement and distraction. Areas of potential harms were related to the activation of emotions that were then unresolved, lack of skill of the art therapist and sudden termination of art therapy. The quality of included qualitative studies was generally low to moderate. In the cost-effectiveness review, a de novo model was constructed and populated with data identified from the clinical review. Scenario analyses were conducted allowing comparisons of group art therapy with wait-list control, group art therapy with group verbal therapy, and individual art therapy versus control. Art therapy appeared cost-effective compared with wait-list control with high certainty, although generalisability to the target population was unclear. Verbal therapy appeared more cost-effective than art therapy but there was considerable uncertainty and a sizeable probability that art therapy was more clinically effective. The cost-effectiveness of individual art therapy was uncertain and dependent on assumptions regarding clinical benefit and duration of benefit. CONCLUSIONS: From the limited available evidence, art therapy was associated with positive effects when compared with a control in a number of studies in patients with different clinical profiles, and it was reported to be an acceptable treatment and was associated with a number of benefits. Art therapy appeared to be cost-effective compared with wait-list but further studies are needed to confirm this finding as well as evidence to inform future cost-effective analyses of art therapy versus other treatments. STUDY REGISTRATION: The study is registered as PROSPERO CRD42013003957. FUNDING: The National Institute for Health Research Health Technology Assessment programme.