Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data.

Background: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. Methods: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. Results: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. Conclusions: TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. Registration: PROSPERO-ID: CRD42023451628.

There is a need for more effective treatments for psychosis, including schizophrenia. Psychosis is a collection of mental health symptoms, such as hearing voices, that can cause distress and impair functioning. These symptoms are thought to be caused by changes in a chemical messenger system in the brain called dopamine. Currently used antipsychotic medications target brain receptors that respond to dopamine. They are not effective in some people and can cause uncomfortable adverse events, such as weight gain and movement disorders, especially with long-term use. A new type of drug is the trace amine-associated receptor 1 (TAAR1) agonists. These drugs act on different brain receptors that can affect the activity of the dopamine system, but do not directly bind to dopamine receptors. We aimed to understand if TAAR1 agonists can reduce symptoms of psychosis, what adverse events they might have, and how they work. We did this by reviewing and collating all available evidence until November 2023. This is a "living" systematic review, so it will be regularly updated in the future. We looked at both human and animal studies investigating TAAR1 agonists. Human studies suggested that two TAAR1 agonists (namely, ulotaront or ralmitaront) might have little to no effect on reducing symptoms of psychosis compared to placebo in people with schizophrenia. They seemed to cause fewer adverse events than current antipsychotics. Data from animal studies suggested that TAAR1 agonists had some positive effects but potentially smaller than other antipsychotics. There were little to no data from both human and animal studies about how TAAR1 agonists actually work. From the current evidence we are uncertain about these results. With the ongoing development of new TAAR1 agonists, more evidence is needed to understand their potential role in the treatment of psychosis.

Assessing the impact of obesity interventions in the early years: a systematic review of UK-based studies.

OBJECTIVES: Childhood obesity rates in the UK are high. The early years of childhood are critical for establishing healthy behaviours and offer interventional opportunities. We aimed to identify studies evaluating the impact of UK-based obesity interventions in early childhood. DESIGN: Systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: Nine databases were searched in March 2023. ELIGIBILITY CRITERIA: We included UK-based obesity intervention studies delivered to children aged 6 months to 5 years that had diet and/or physical activity components and reported anthropometric outcomes. The primary outcome of interest was z-score Body Mass Index (zBMI) change (within and between subjects). Studies evaluating the effects of breastfeeding interventions were not included as obesity prevention interventions, given that best-practice formula feeding is also likely to encourage healthy growth. The publication date for studies was limited to the previous 12 years (2011-23), as earlier reviews found few evaluations of interventions in the UK. DATA EXTRACTION AND SYNTHESIS: The reviewers worked independently using standardised approach to search, screen and code the included studies. Risk of bias was assessed using Cochrane tools (ROB 2 or ROBINS-I). RESULTS: Six trials (five studies) were identified, including two randomised controlled trials (RCT), one cluster randomised trial (CRT), two feasibility CRTs and one impact assessment. The total number of participants was 566. Three trials focused on disadvantaged families and two included high-risk children categorised as having overweight or obesity. Compared with baseline, five interventions reported reductions in zBMI, three of which were statistically significant (p<0.05). Compared with control, five interventions showed zBMI reductions, one of which was significant. Only two trials were followed up beyond 12 months. All studies were found to have a high risk of bias. Meta-analysis was not possible due to the heterogeneity of studies. CONCLUSION: UK evidence was limited but some interventions showed promising results in promoting healthy growth. As part of a programme of policies, interventions in the early years may have an important role in reducing the risk of childhood obesity. PROSPERO REGISTRATION NUMBER: CRD42021290676.

The implementation of embedded researchers in policy, public services, and commercial settings: a systematic evidence and gap map.

BACKGROUND: Embedding researchers into policy and other settings may enhance research capacity within organisations to enable them to become more research active. We aimed to generate an evidence map on evaluations of embedded researcher interventions to (i) identify where systematic reviews and primary research are needed and (ii) develop conceptual understandings of 'embedded researchers'. We define 'embedded researchers' through a set of principles that incorporate elements such as the aim of activities, the types of relationships and learning involved, and the affiliations and identities adopted. METHODS: We included studies published across all sectors, searching fourteen databases, other web sources and two journals for evaluations published between 1991 and spring 2021. Data were extracted using a coding tool developed for this study. We identified new typologies of embedded researcher interventions through undertaking Latent Class Analysis. RESULTS: The map describes 229 evaluations spanning a variety of contexts. Our set of principles allowed us to move beyond a narrow focus on embedded researchers in name alone, towards consideration of the wide range of roles, activities, identities, and affiliations related to embedded researchers. We identified 108 different allied terms describing an embedded researcher. Embedded researcher activity spanned a continuum across lines of physical, cultural, institutional, and procedural embeddedness (from weaker to more intense forms of embeddedness) and took a range of forms that bridge or blur boundaries between academia and policy/practice. CONCLUSIONS: We developed a broad map of international embedded researcher activity in a wide range of sectors. The map suggests that embedded researcher interventions occupy a broader suite of models than previously acknowledged and our findings also offer insight on the type and nature of this literature. Given the clear policy interest in this area, a better understanding of the processes involved with becoming embedded within an organisation is needed. Further work is also necessary to address the challenges of evaluating the work of embedded researchers, including consideration for which outcome measures are most appropriate, to better understand their influence.

What are the mechanisms driving the early stages of embedded researcher interventions? A qualitative process evaluation in English local government.

Improved collaboration and communication between public health practitioners and academia could enhance the flow of research evidence into policy and practice. Embedded researchers present one type of intervention with the potential to bridge the research-implementation gap through their dual affiliations with decision makers and academia. Although embedded researcher posts are garnering increasing attention in public health, there remains a need to understand the mechanisms through which they may promote the translation of evidence into practice. To address this gap, we conducted a processes evaluation incorporating data from seventeen semi-structured interviews with embedded researchers in local government public health teams across England. We aimed to expand theoretical understandings of embedded researchers in public health through providing a detailed conceptualisation of the mechanisms shaping the early stages of their roles. Interviews with embedded researchers were conducted from late 2021 to spring 2022. Our results suggest that the initial months of embedded researcher roles are defined by a lengthy embedding phase centred on building trust and gathering contextual knowledge. This phase forms the foundation on which these interventions are built. We identified seven categories of outputs delivered by embedded researchers which primarily revolved around building research capacity and addressed many of the primary barriers limiting research activity in public health. Improvements in research awareness, interest, and involvement reflected early changes in local research cultures. However, our results align with previous work suggesting that changing an organisational research culture is a long-term process. Expectations for embedded researchers should thus be proportionate to the seniority and scale of the post and we add our voice to calls for sustained investment in these valuable interventions. Further examination of how embedded researcher roles evolve over time in public health is necessary to broaden understandings of the concept of embeddedness in these settings.

Pro-dopaminergic pharmacological interventions for anhedonia in depression: protocol for a living systematic review of human and non-human studies.

Background: Anhedonia is a key symptom of depression, and it has been suggested as a potential target for future individualised treatments. However, much is unknown about how interventions enhancing dopaminergic pathways may affect anhedonia symptoms in the context of depression. Methods: We will perform independent searches in multiple electronic databases to identify clinical and animal experimental studies on pro-dopaminergic interventions in individuals with depression or animal models for depression. The primary outcomes will be overall anhedonia symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures. At least two independent reviewers will conduct the study selection, data extraction, and risk of bias assessments using pre-defined tools according to each record's study design. We will develop ontologies to facilitate study identification and data extraction. We will synthesise data from clinical and animal studies separately. If appropriate, we will use random-effects meta-analyses, or synthesis without meta-analyses. We will investigate study characteristics as potential sources of heterogeneity. We will evaluate the confidence in the evidence for each outcome and source of evidence, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, we will draw an overall conclusion in a triangulation meeting involving a multidisciplinary team of experts. We plan updates of the review every 6 months, and any future modifications to the protocol will be documented. We will co-produce this review with multiple stakeholders. PROSPERO registration: CRD42023451821.

Trace amine-associated receptor 1 (TAAR1) agonists for psychosis: protocol for a living systematic review and meta-analysis of human and non-human studies.

BACKGROUND: There is an urgent need to develop more effective and safer antipsychotics beyond dopamine 2 receptor antagonists. An emerging and promising approach is TAAR1 agonism. Therefore, we will conduct a living systematic review and meta-analysis to synthesize and triangulate the evidence from preclinical animal experiments and clinical studies on the efficacy, safety, and underlying mechanism of action of TAAR1 agonism for psychosis. METHODS: Independent searches will be conducted in multiple electronic databases to identify clinical and animal experimental studies comparing TAAR1 agonists with licensed antipsychotics or other control conditions in individuals with psychosis or animal models for psychosis, respectively. The primary outcomes will be overall psychotic symptoms and their behavioural proxies in animals. Secondary outcomes will include side effects and neurobiological measures. Two independent reviewers will conduct study selection, data extraction using predefined forms, and risk of bias assessment using suitable tools based on the study design. Ontologies will be developed to facilitate study identification and data extraction. Data from clinical and animal studies will be synthesized separately using random-effects meta-analysis if appropriate, or synthesis without meta-analysis. Study characteristics will be investigated as potential sources of heterogeneity. Confidence in the evidence for each outcome and source of evidence will be evaluated, considering the summary of the association, potential concerns regarding internal and external validity, and reporting biases. When multiple sources of evidence are available for an outcome, an overall conclusion will be drawn in a triangulation meeting involving a multidisciplinary team of experts. We plan trimonthly updates of the review, and any modifications in the protocol will be documented. The review will be co-produced by multiple stakeholders aiming to produce impactful and relevant results and bridge the gap between preclinical and clinical research on psychosis. PROTOCOL REGISTRATION: PROSPERO-ID: CRD42023451628.

Advertising and Young People's Critical Reasoning Abilities: Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Young people are exposed to an abundance of advertising for unhealthy products (eg, unhealthy foods, tobacco, alcohol). Because of their developing cognition, children may not be able to understand the intent of advertising. However, advertising restrictions often assume that adolescents have critical reasoning capacity and can resist the effects of advertising. This review seeks to assess whether the evidence supports this assumption. METHODS: Ten databases were searched in December 2020. Inclusion criteria were participants aged 6 to 17 years, any advertising exposure, objectively measured understanding or attitudinal outcome, a comparison, control, and between-group comparison. This study included all languages and excluded studies published pre-2010. Two reviewers independently extracted data and assessed study quality. RESULTS: Thirty-eight articles were included. Meta-analysis of 9 studies with attitudinal outcomes indicated that unhealthy product advertising generated more positive brand or product attitudes compared with neutral or no advertising control in all ages. There were significant effects for digital and nondigital advertising formats. We found greater understanding did not protect against the impact of advertising on brand or product attitudes. Limitations include the inability to meta-analyze the impact of advertising on understanding or the influence of age. CONCLUSIONS: Evidence shows that the attitudes of young people were influenced by advertising. Critical reasoning abilities did not appear to be fully developed during adolescence and not found to be protective against the impact of advertising. Policymakers should ensure regulations to restrict marketing of unhealthy commodities protects adolescents as well as younger children.

Using systems perspectives in evidence synthesis: A methodological mapping review.

Reviewing complex interventions is challenging because they include many elements that can interact dynamically in a nonlinear manner. A systems perspective offers a way of thinking to help understand complex issues, but its application in evidence synthesis is not established. The aim of this project was to understand how and why systems perspectives have been applied in evidence synthesis. A methodological mapping review was conducted to identify papers using a systems perspective in evidence synthesis. A search was conducted in seven bibliographic databases and three search engines. A total of 101 papers (representing 98 reviews) met the eligibility criteria. Two categories of reviews were identified: (1) reviews using a "systems lens" to frame the topic, generate hypotheses, select studies, and guide the analysis and interpretation of findings (n = 76) and (2) reviews using systems methods to develop a systems model (n = 22). Several methods (e.g., systems dynamic modeling, soft systems approach) were identified, and they were used to identify, rank and select elements, analyze interactions, develop models, and forecast needs. The main reasons for using a systems perspective were to address complexity, view the problem as a whole, and understand the interrelationships between the elements. Several challenges for capturing the true nature and complexity of a problem were raised when performing these methods. This review is a useful starting point when designing evidence synthesis of complex interventions. It identifies different opportunities for applying a systems perspective in evidence synthesis, and highlights both commonplace and less familiar methods.

The impact on dietary outcomes of licensed and brand equity characters in marketing unhealthy foods to children: A systematic review and meta-analysis.

Licensed and brand equity characters are used to target children in the marketing of products high in fat, salt, and sugar (HFSS), but the impact of characters on dietary outcomes is unclear. The primary aim of this review was to quantify the impact of both licensed and brand equity characters on children's dietary outcomes given that existing regulations often differentiates between these character types. We systematically searched eight interdisciplinary databases and included studies from 2009 onwards until August 2021, including all countries and languages. Participants were children under 16 years, exposure was marketing for HFSS product with a character, and the outcomes were dietary consumption, preference, or purchasing behaviors of HFSS products. Data allowed for meta-analysis of taste preferences. A total of 16 articles (including 20 studies) met the inclusion criteria, of which five were included in the meta-analysis. Under experimental conditions, the use of characters on HFSS packaging compared with HFSS packaging with no character was found to result in significantly higher taste preference for HFSS products (standardized mean difference on a 5-point scale 0.273; p < 0.001). Narrative findings supported this, with studies reporting impact of both character types on product preferences including food liking and snack choice. There was limited evidence on the impact on purchase behaviors and consumption. These findings are supportive of policies that limit the exposure of HFSS food marketing using characters to children.

The Impact on Dietary Outcomes of Celebrities and Influencers in Marketing Unhealthy Foods to Children: A Systematic Review and Meta-Analysis.

Celebrities, including influencers, are commonly used to market products that are high in fat, sugar, and salt (HFSS) to children but the impact on dietary outcomes has been unclear. The primary aim of this study was to systematically review the literature and quantify the impact of celebrities in HFSS marketing on children's dietary outcomes. We searched eight databases and included studies from all countries and languages published from 2009 until August 2021. Participants were defined as under 16 years, exposure was marketing for HFSS products with a celebrity, and the outcomes were dietary preference, purchasing behaviors, and consumption of HFSS products. We were able to conduct a meta-analysis for consumption outcomes. Seven articles met the inclusion criteria, of which three were included in the meta-analysis. Under experimental conditions, the use of celebrities in HFSS marketing compared to non-food marketing was found to significantly increase consumption of the marketed HFSS product by 56.4 kcals (p = 0.021). There was limited evidence on the impact on preference or purchase intentions and on the comparisons between use and non-use of celebrities and influencers.

Consumption and effects of caffeinated energy drinks in young people: an overview of systematic reviews and secondary analysis of UK data to inform policy.

BACKGROUND: This overview and analysis of UK datasets was commissioned by the UK government to address concerns about children's consumption of caffeinated energy drinks and their effects on health and behaviour. METHODS: We searched nine databases for systematic reviews, published between 2013 and July 2021, in English, assessing caffeinated energy drink consumption by people under 18 years old (children). Two reviewers rated or checked risk of bias using AMSTAR2, and extracted and synthesised findings. We searched the UK Data Service for country-representative datasets, reporting children's energy-drink consumption, and conducted bivariate or latent class analyses. RESULTS: For the overview, we included 15 systematic reviews; six reported drinking prevalence and 14 reported associations between drinking and health or behaviour. AMSTAR2 ratings were low or critically low. Worldwide, across reviews, from 13% to 67% of children had consumed energy drinks in the past year. Only two of the 74 studies in the reviews were UK-based. For the dataset analysis, we identified and included five UK cross-sectional datasets, and found that 3% to 32% of children, across UK countries, consumed energy drinks weekly, with no difference by ethnicity. Frequent drinking (5 or more days per week) was associated with low psychological, physical, educational and overall well-being. Evidence from reviews and datasets suggested that boys drank more than girls, and drinking was associated with more headaches, sleep problems, alcohol use, smoking, irritability, and school exclusion. GRADE (Grading of Recommendations, Assessment, Development and Evaluation) assessment suggests that the evidence is weak. CONCLUSIONS: Weak evidence suggests that up to a third of children in the UK consume caffeinated energy drinks weekly; and drinking 5 or more days per week is associated with some health and behaviour problems. Most of the evidence is from surveys, making it impossible to distinguish cause from effect. Randomised controlled trials are unlikely to be ethical; longitudinal studies could provide stronger evidence. PROSPERO REGISTRATIONS: CRD42018096292 - no deviations. CRD42018110498 - one deviation - a latent class analysis was conducted.

School Closures During Social Lockdown and Mental Health, Health Behaviors, and Well-being Among Children and Adolescents During the First COVID-19 Wave: A Systematic Review.

IMPORTANCE: School closures as part of broader social lockdown measures during the COVID-19 pandemic may be associated with the health and well-being of children and adolescents. OBJECTIVE: To review published reports on the association of school closures during broader social lockdown with mental health, health behaviors, and well-being in children and adolescents aged 0 to 19 years, excluding associations with transmission of infection. EVIDENCE REVIEW: Eleven databases were searched from inception to September 2020, and machine learning was applied for screening articles. A total of 16 817 records were screened, 151 were reviewed in full text, and 36 studies were included. Quality assessment was tailored to study type. A narrative synthesis of results was undertaken because data did not allow meta-analysis. FINDINGS: A total of 36 studies from 11 countries were identified, involving a total of 79 781 children and adolescents and 18 028 parents, which occurred during the first wave of the COVID-19 pandemic (February to July 2020). All evaluated school closure as part of broader social lockdown during the first COVID-19 wave, and the duration of school closure ranged from 1 week to 3 months. Of those, 9 (25%) were longitudinal pre-post studies, 5 (14%) were cohort, 21 (58%) were cross-sectional, and 1 (3%) was a modeling study. Thirteen studies (36%) were high quality, 17 (47%) were medium quality, and 6 (17%) were low quality. Twenty-three studies (64%) were published, 8 (22%) were online reports, and 5 (14%) were preprints. Twenty-five studies (69%) concerning mental health identified associations across emotional, behavioral, and restlessness/inattention problems; 18% to 60% of children and adolescents scored above risk thresholds for distress, particularly anxiety and depressive symptoms, and 2 studies reported no significant association with suicide. Three studies reported that child protection referrals were lower than expected number of referrals originating in schools. Three studies suggested higher screen time usage, 2 studies reported greater social media use, and 6 studies reported lower physical activity. Studies on sleep (10 studies) and diet (5 studies) provided inconclusive evidence on harms. CONCLUSIONS AND RELEVANCE: In this narrative synthesis of reports from the first wave of the COVID-19 pandemic, studies of short-term school closures as part of social lockdown measures reported adverse mental health symptoms and health behaviors among children and adolescents. Associations between school closure and health outcomes and behaviors could not be separated from broader lockdown measures.

Applying machine classifiers to update searches: Analysis from two case studies.

Manual screening of citation records could be reduced by using machine classifiers to remove records of very low relevance. This seems particularly feasible for update searches, where a machine classifier can be trained from past screening decisions. However, feasibility is unclear for broad topics. We evaluate the performance and implementation of machine classifiers for update searches of public health research using two case studies. The first study evaluates the impact of using different sets of training data on classifier performance, comparing recall and screening reduction with a manual screening 'gold standard'. The second study uses screening decisions from a review to train a classifier that is applied to rank the update search results. A stopping threshold was applied in the absence of a gold standard. Time spent screening titles and abstracts of different relevancy-ranked records was measured. Results: Study one: Classifier performance varies according to the training data used; all custom-built classifiers had a recall above 93% at the same threshold, achieving screening reductions between 41% and 74%. Study two: applying a classifier provided a solution for tackling a large volume of search results from the update search, and screening volume was reduced by 61%. A tentative estimate indicates over 25 h screening time was saved. In conclusion, custom-built machine classifiers are feasible for reducing screening workload from update searches across a range of public health interventions, with some limitation on recall. Key considerations include selecting a training dataset, agreeing stopping thresholds and processes to ensure smooth workflows.

Interventions to support people exposed to adverse childhood experiences: systematic review of systematic reviews.

BACKGROUND: Adverse Childhood Experiences (ACEs) such as abuse, neglect or household adversity may have a range of serious negative impacts. There is a need to understand what interventions are effective to improve outcomes for people who have experienced ACEs. METHODS: Systematic review of systematic reviews. We searched 18 database sources from 2007 to 2018 for systematic reviews of effectiveness data on people who experienced ACEs aged 3-18, on any intervention and any outcome except incidence of ACEs. We included reviews with a summary quality score (AMSTAR) of 5.5 or above. RESULTS: Twenty-five reviews were included. Most reviews focus on psychological interventions and mental health outcomes. The strongest evidence is for cognitive-behavioural therapy for people exposed to abuse. For other interventions - including psychological therapies, parent training, and broader support interventions - the findings overall are inconclusive, although there are some positive results. CONCLUSIONS: There are significant gaps in the evidence on interventions for ACEs. Most approaches focus on mitigating individual psychological harms, and do not address the social pathways which may mediate the negative impacts of ACEs. Many negative impacts of ACEs (e.g. on health behaviours, social relationships and life circumstances) have also not been widely addressed by intervention studies.

School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review.

In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2-4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.

Cyberbullying and Children and Young People's Mental Health: A Systematic Map of Systematic Reviews.

Cyberbullying is associated with considerable negative mental and psychosocial consequences in children and young people, making it a serious public health concern. To review the highest level of available evidence, a systematic mapping review was conducted to identify systematic reviews that investigated the relationship between cyberbullying and mental and psychological outcomes in young people. Topic-relevant bibliographic databases and online resources were searched to identify reviews published since 2007. Data were extracted using a coding tool developed for this study. Methodological quality of included reviews was assessed using AMSTAR criteria. Nineteen systematic reviews satisfied the inclusion criteria and they reported a strong negative association between cyberbullying and mental health outcomes in young people. Meta-analysis was performed in 11 reviews and narrative synthesis in 8 reviews. Data were derived from predominantly cross-sectional studies and a clear causal relationship between cyberbullying and mental outcomes cannot be established. Two-third of the included reviews were classified to be of low or unclear quality, due to the lack of quality assessment of the primary studies included in individual reviews. This systematic map consolidates available evidence at review level and confirms the existing gaps in longitudinal and qualitative evidence synthesis. Closer examination of the moderating factors influencing cyberbullying behaviors in future research can advance our understanding and inform the development of tailored programs of intervention to mitigate the negative impact of this phenomenon.

Healing The Past By Nurturing The Future: A qualitative systematic review and meta-synthesis of pregnancy, birth and early postpartum experiences and views of parents with a history of childhood maltreatment.

BACKGROUND: Child maltreatment can have serious effects on development and physical, social and emotional wellbeing. Any long-lasting relational effects can impede the capacity to nurture children, potentially leading to 'intergenerational trauma'. Conversely, the transition to parenthood during pregnancy, birth and the early postpartum period offers a unique life-course opportunity for healing. This systematic review aims to understand the pregnancy, birth and early postpartum experiences of parents who reported maltreatment in their own childhood. METHODS: A protocol, based on the ENTREQ statement, was registered with PROSPERO. We searched Medline, PsycINFO, CINAHL, EMBASE, NHS Evidence and key Web of Science databases from date of inception to June 2018 to identify qualitative studies exploring perinatal experiences of parents who were maltreated in their own childhood. Two reviewers independently screened articles for inclusion and extracted data. Data were synthesised using grounded theory and thematic analysis approaches. FINDINGS: The search yielded 18329 articles, 568 full text articles were reviewed, and 50 studies (60 articles) met inclusion criteria for this review. Due to the large number of studies across the whole perinatal period (pregnancy to two years postpartum), this paper reports findings for experiences during pregnancy, birth and early postpartum (27 studies). Parents described positive experiences and strategies to help them achieve their hopes and dreams of providing safe, loving and nurturing care for their children. However, many parents experienced serious challenges. Seven core analytic themes encapsulated these diverse and dynamic experiences: New beginnings; Changing roles and identities; Feeling connected; Compassionate care; Empowerment; Creating safety; and Reweaving a future. CONCLUSIONS: Pregnancy birth and the early postpartum period is a unique life-course healing opportunity for parents with a history of maltreatment. Understanding parent's experiences and views of perinatal care and early parenting is critical for informing the development of acceptable and effective support strategies.

How Do Contextual Factors Influence Implementation and Receipt of Positive Youth Development Programs Addressing Substance Use and Violence? A Qualitative Meta-Synthesis of Process Evaluations.

OBJECTIVE: Positive youth development (PYD) often aims to prevent tobacco, alcohol, and drugs use and violence. We systematically reviewed PYD interventions, synthesizing process, and outcomes evidence. Synthesis of outcomes, published elsewhere, found no overall evidence of reducing substance use or violence but notable variability of fidelity. Our synthesis of process evaluations examined how implementation varied and was influenced by context. DATA SOURCE: Process evaluations of PYD aiming to reduce substance use and violence. Study Inclusion Criteria: Overall review published since 1985; written in English; focused on youth aged 11 to 18 years; focused on interventions addressing multiple positive assets; reported on theory, process, or outcomes; and concerned with reducing substance use or violence. Synthesis of process evaluations examined how implementation varies with or is influenced by context. DATA EXTRACTION: Two reviewers in parallel. DATA SYNTHESIS: Thematic synthesis. RESULTS: We identified 12 reports. Community engagement enhanced program appeal. Collaboration with other agencies could broaden the activities offered. Calm but authoritative staff increased acceptability. Staff continuity underpinned diverse activities and durable relationships. Empowering participants were sometimes in tension with requiring them to engage in diverse activities. CONCLUSION: Our systematic review identified factors that might help improve the fidelity and acceptability of PYD interventions. Addressing these might enable PYD to fulfill its potential as a means of promoting health.

Exercise interventions and patient beliefs for people with hip, knee or hip and knee osteoarthritis: a mixed methods review.

BACKGROUND: Chronic peripheral joint pain due to osteoarthritis (OA) is extremely prevalent and a major cause of physical dysfunction and psychosocial distress. Exercise is recommended to reduce joint pain and improve physical function, but the effect of exercise on psychosocial function (health beliefs, depression, anxiety and quality of life) in this population is unknown. OBJECTIVES: To improve our understanding of the complex inter-relationship between pain, psychosocial effects, physical function and exercise. SEARCH METHODS: Review authors searched 23 clinical, public health, psychology and social care databases and 25 other relevant resources including trials registers up to March 2016. We checked reference lists of included studies for relevant studies. We contacted key experts about unpublished studies. SELECTION CRITERIA: To be included in the quantitative synthesis, studies had to be randomised controlled trials of land- or water-based exercise programmes compared with a control group consisting of no treatment or non-exercise intervention (such as medication, patient education) that measured either pain or function and at least one psychosocial outcome (self-efficacy, depression, anxiety, quality of life). Participants had to be aged 45 years or older, with a clinical diagnosis of OA (as defined by the study) or self-reported chronic hip or knee (or both) pain (defined as more than six months' duration).To be included in the qualitative synthesis, studies had to have reported people's opinions and experiences of exercise-based programmes (e.g. their views, understanding, experiences and beliefs about the utility of exercise in the management of chronic pain/OA). DATA COLLECTION AND ANALYSIS: We used standard methodology recommended by Cochrane for the quantitative analysis. For the qualitative analysis, we extracted verbatim quotes from study participants and synthesised studies of patients' views using framework synthesis. We then conducted an integrative review, synthesising the quantitative and qualitative data together. MAIN RESULTS: Twenty-one trials (2372 participants) met the inclusion criteria for quantitative synthesis. There were large variations in the exercise programme's content, mode of delivery, frequency and duration, participant's symptoms, duration of symptoms, outcomes measured, methodological quality and reporting. Comparator groups were varied and included normal care; education; and attention controls such as home visits, sham gel and wait list controls. Risk of bias was high in one and unclear risk in five studies regarding the randomisation process, high for 11 studies regarding allocation concealment, high for all 21 studies regarding blinding, and high for three studies and unclear for five studies regarding attrition. Studies did not provide information on adverse effects.There was moderate quality evidence that exercise reduced pain by an absolute percent reduction of 6% (95% confidence interval (CI) -9% to -4%, (9 studies, 1058 participants), equivalent to reducing (improving) pain by 1.25 points from 6.5 to 5.3 on a 0 to 20 scale and moderate quality evidence that exercise improved physical function by an absolute percent of 5.6% (95% CI -7.6% to 2.0%; standardised mean difference (SMD) -0.27, 95% CI -0.37 to -0.17, equivalent to reducing (improving) WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) function on a 0 to 100 scale from 49.9 to 44.3) (13 studies, 1599 participants)). Self-efficacy was increased by an absolute percent of 1.66% (95% CI 1.08% to 2.20%), although evidence was low quality (SMD 0.46, 95% CI 0.34 to 0.58, equivalent to improving the ExBeliefs score on a 17 to 85 scale from 64.3 to 65.4), with small benefits for depression from moderate quality evidence indicating an absolute percent reduction of 2.4% (95% CI -0.47% to 0.5%) (SMD -0.16, 95% CI -0.29 to -0.02, equivalent to improving depression measured using HADS (Hospital Anxiety and Depression Scale) on a 0 to 21 scale from 3.5 to 3.0) but no clinically or statistically significant effect on anxiety (SMD -0.11, 95% CI -0.26 to 0.05, 2% absolute improvement, 95% CI -5% to 1% equivalent to improving HADS anxiety on a 0 to 21 scale from 5.8 to 5.4; moderate quality evidence). Five studies measured the effect of exercise on health-related quality of life using the 36-item Short Form (SF-36) with statistically significant benefits for social function, increasing it by an absolute percent of 7.9% (95% CI 4.1% to 11.6%), equivalent to increasing SF-36 social function on a 0 to 100 scale from 73.6 to 81.5, although the evidence was low quality. Evidence was downgraded due to heterogeneity of measures, limitations with blinding and lack of detail regarding interventions. For 20/21 studies, there was a high risk of bias with blinding as participants self-reported and were not blinded to their participation in an exercise intervention.Twelve studies (with 6 to 29 participants) met inclusion criteria for qualitative synthesis. Their methodological rigour and quality was generally good. From the patients' perspectives, ways to improve the delivery of exercise interventions included: provide better information and advice about the safety and value of exercise; provide exercise tailored to individual's preferences, abilities and needs; challenge inappropriate health beliefs and provide better support.An integrative review, which compared the findings from quantitative trials with low risk of bias and the implications derived from the high-quality studies in the qualitative synthesis, confirmed the importance of these implications. AUTHORS' CONCLUSIONS: Chronic hip and knee pain affects all domains of people's lives. People's beliefs about chronic pain shape their attitudes and behaviours about how to manage their pain. People are confused about the cause of their pain, and bewildered by its variability and randomness. Without adequate information and advice from healthcare professionals, people do not know what they should and should not do, and, as a consequence, avoid activity for fear of causing harm. Participation in exercise programmes may slightly improve physical function, depression and pain. It may slightly improve self-efficacy and social function, although there is probably little or no difference in anxiety. Providing reassurance and clear advice about the value of exercise in controlling symptoms, and opportunities to participate in exercise programmes that people regard as enjoyable and relevant, may encourage greater exercise participation, which brings a range of health benefits to a large population of people.

Text mining for search term development in systematic reviewing: A discussion of some methods and challenges.

Using text mining to aid the development of database search strings for topics described by diverse terminology has potential benefits for systematic reviews; however, methods and tools for accomplishing this are poorly covered in the research methods literature. We briefly review the literature on applications of text mining for search term development for systematic reviewing. We found that the tools can be used in 5 overarching ways: improving the precision of searches; identifying search terms to improve search sensitivity; aiding the translation of search strategies across databases; searching and screening within an integrated system; and developing objectively derived search strategies. Using a case study and selected examples, we then reflect on the utility of certain technologies (term frequency-inverse document frequency and Termine, term frequency, and clustering) in improving the precision and sensitivity of searches. Challenges in using these tools are discussed. The utility of these tools is influenced by the different capabilities of the tools, the way the tools are used, and the text that is analysed. Increased awareness of how the tools perform facilitates the further development of methods for their use in systematic reviews.