Search

Aims In a laboratory, disinfectants used to inactivate pathogens on contaminated surfaces and to prevent spread of diseases often have adverse side effects on personnel and the environment. It is, therefore, essential to find safer, fast-acting and yet effective disinfectants. The objective of this study was to evaluate an accelerated hydrogen peroxide® ( AHP®)-based disinfectant against high consequence foreign animal disease pathogens such as foot-and-mouth disease virus ( FMDV) and swine vesicular disease virus ( SVDV), as well as Senecavirus A ( SVA), which causes similar lesions as FMDV and SVDV. Methods and Results We tested varying dilutions and contact times of AHP against FMDV, SVDV and SVA by the standard US EPA and modified methods. AHP was effective against all three viruses, albeit at a higher concentration and double the manufacturer recommended contact time when testing wet films of SVDV. Conclusions AHP is an effective disinfectant against FMDV, SVDV and SVA. Significance and Impact of the Study AHP-based disinfectant can, therefore, be used in high containment laboratories working with FMDV, SVDV and related pathogens. [ABSTRACT FROM AUTHOR]

Abstract Background For systematic reviews providing evidence for policy decisions in specific geographical regions, there is a need to minimise regional bias when seeking out relevant research studies. Studies on people’s views tend to be dispersed across a range of bibliographic databases and other search sources. It is recognised that a comprehensive literature search can provide unique evidence not found from a focused search; however, the geographical focus of databases as a potential source of bias on the findings of a research review is less clear. This case study describes search source selection for research about people’s views and how supplementary searches designed to redress geographical bias influenced the findings of a systematic review. Our research questions are: a) what was the impact of search methods employed to redress potential database selection bias on the overall findings of the review? and b) how did each search source contribute to the identification of all the research studies included in the review? Methods The contribution of 25 search sources in locating 28 studies included within a systematic review on UK children’s views of body size, shape and weight was analysed retrospectively. The impact of utilising seven search sources chosen to identify UK-based literature on the review’s findings was assessed. Results Over a sixth (5 out of 28) of the studies were located only through supplementary searches of three sources. These five studies were of a disproportionally high quality compared with the other studies in the review. The retrieval of these studies added direction, detail and strength to the overall findings of the review. All studies in the review were located within 21 search sources. Precision for 21 sources ranged from 0.21% to 1.64%. Conclusions For reducing geographical bias and increasing the coverage and context-specificity of systematic reviews of people’s perspectives and experiences, searching that is sensitive and aimed at reducing geographical bias in database sources is recommended.

This paper summarizes the present position of agricultural spray irrigation in England and Wales, providing (a) national statistics and regional information, (b) the reasons why farmers irrigate, (c) the place of agriculture in the economy, and (d) the value of irrigation. Areview of the Ministry of Agriculture, Fisheries and Food irrigationsurveys highlights the important crops in terms of area and volume of water used, sources of water and storage, and application methods. The predictions for the future, including the effects of climate change are reviewed with examples of how farmers, the EA, and the agricultural industry, are helping to overcome problems. [ABSTRACT FROM AUTHOR]

Individuals with excess weight are at a higher risk for various physical and mental health conditions. Interventions targeting weight loss can improve health, with modest weight loss of five to ten percent of body weight often considered clinically meaningful for enhancing health outcomes. However, the benefits of achieving low-level weight loss ( < 5% body weight) are poorly understood. We aimed to systematically review relevant literature and synthesise the evidence that assessed the potential health benefits of losing less than five percent body weight. We searched seven academic databases and included studies in any language, from any country, with no time constraints. We included any intervention studies that assessed the impact of less than five percent weight loss on any measured physical or mental health markers or indices. 70 studies from 68 articles were included, with study participants ranging from 14 to 10,742. In total, 137 health markers were assessed, categorised into metabolic markers (n = 42), cardiovascular markers (n = 32), anthropometric measures (n = 19), quality of life indices (n = 10), inflammatory biomarkers (n = 10), renal and hepatic markers (n = 9), psychosocial and behavioural measures (n = 8), pulmonary function (n = 3), total mortality (n = 2), ovulatory function (n = 1), and muscle strength (n = 1). Overall, 60% of studies reported improvements, 37% found no change or mixed results, and 3% observed a worsening of health markers or indices. Based on the available data, 87% of participants (n = 15,839) in the studies reported improvements in health markers or indices as a result of low-level weight loss. Our findings suggest that low-level weight loss can lead to various health benefits and challenges the conventional threshold for effective weight loss.Preregistration The review protocol was pre-registered with PROSPERO (CRD42023406342)., (© 2024. Crown.)

Efforts to reconcile development and evolution have demonstrated that development is biased, with phenotypic variation being more readily produced in certain directions. However, how this "developmental bias" can influence micro- and macroevolution is poorly understood. In this review, we demonstrate that defining features of adaptive radiations suggest a role for developmental bias in driving adaptive divergence. These features are i) common ancestry of developmental systems; ii) rapid evolution along evolutionary "lines of least resistance;" iii) the subsequent repeated and parallel evolution of ecotypes; and iv) evolutionary change "led" by biased phenotypic plasticity upon exposure to novel environments. Drawing on empirical and theoretical data, we highlight the reciprocal relationship between development and selection as a key driver of evolutionary change, with development biasing what variation is exposed to selection, and selection acting to mold these biases to align with the adaptive landscape. Our central thesis is that developmental biases are both the causes and consequences of adaptive radiation and divergence. We argue throughout that incorporating development and developmental bias into our thinking can help to explain the exaggerated rate and scale of evolutionary processes that characterize adaptive radiations, and that this can be best achieved by using an eco-evo-devo framework incorporating evolutionary biology, development, and ecology. Such a research program would demonstrate that development is not merely a force that imposes constraints on evolution, but rather directs and is directed by evolutionary forces. We round out this review by highlighting key gaps in our understanding and suggest further research programs that can help to resolve these issues., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stansfield and Parsons.)

Background/Objectives : Low quality diets are a risk factor for non-communicable diseases; therefore, improving diet quality is a public health and policy priority in the UK and elsewhere. Reformulating food/beverage products to make them healthier may be an effective approach. Evidence suggests that fiscal interventions, notably taxes/levies on soft drinks, can lead to reformulation but the evidence for voluntary or mandated non-fiscal interventions is less clear. We aimed to review and synthesise contemporary evidence to determine whether non-fiscal policies/interventions result in the reformulation of food/beverage products Methods : In April 2023, we systematically searched ten international academic and nine grey literature databases. We included real-world study designs, all nutrients, in- and out-of-home sectors, and studies published from 2013, to ensure policy relevancy. We excluded modelling studies. Using the Synthesis Without Meta-Analysis method we conducted vote counting of studies based on the direction of effect and narrative synthesis by intervention type. Risk of bias was assessed using a tool developed by the EPPI-Centre and quality was assessed using GRADE. Results : We included 77 real-world studies from 19 countries, reporting 100 non-fiscal policies/interventions. Most commonly, these were reduction targets ( n = 44), front-of-pack labels ( n = 23), and advertising standards ( n = 9). Most interventions were voluntary ( n = 67), compared to mandatory ( n = 33), and focused on the in-home sector ( n = 63). The vote counting results showed non-fiscal policies/interventions overall led to improvements in reformulation in 60/63 studies with a valid direction of effect (95%, 95% CI 0.869, 0.984, p < 0.001). Mandatory implementations were more successful than voluntary implementations with 15/15 showing an improvement (100%, 95% CI 0.796, 1], p < 0.001), compared 40/43 showing an improvement (93%, 95% CI 0.814, 0.976, p < 0.001). Most of the studies were of low quality, due to the observational nature of the studies. Sodium was the most commonly targeted nutrient ( n = 56) and was found to be reformulated in most studies. Causation is difficult to establish from real-world studies, but evidence suggests that regulatory and multi-component strategies may be effective at driving reformulation. Conclusions: Non-fiscal policies/interventions can play an important role in driving reformulation, alongside fiscal measures. This work was funded by the National Institute for Health and Care Research PRP-PRU-02-15-Healthy Weight and registered on Open Science Framework.

Objective: To consider the approaches within Web of Science Core Collection (WoSCC) databases for limiting geographically. To compare the limits to an adaptation of NICE's UK MEDLINE filter for use on WoSCC databases., Methods: We tested and appraised the inbuilt functions and search field options that support identification by countries/regions and affiliations. We compared these with an adapted filter to identify healthcare research on or about the UK. We calculated the recall of the inbuilt limits and filter using 177 studies and investigated why records were missed. We also calculated the percentage reduction of the overall number-needed-to-screen (ONNS)., Results: Inbuilt limits within WoSCC enable identification of research from specific countries/regions or affiliations if there is data in the address field. Refining by affiliations allows retrieval of research where affiliations are in the 200 or 500 most frequent for a set of results. An adaptation of the UK MEDLINE filter achieved an average of 97% recall. ONNS was significantly reduced using the filter. However, studies where the countries or regions are only mentioned within the full text or other non-searchable fields will be missed., Conclusion: Information specialists should consider how inbuilt geographic limits operate on WoSCC and whether these are suitable for their research. The adapted filter can sensitively limit to the UK and could be useful for systematic reviews due to its high recall and ability to significantly reduce ONNS. Geographic filters can be feasible to adapt for use on WoSCC databases (where similar search fields are used between platforms)., (Copyright © 2024 Helen A. Fulbright, Claire Stansfield.)

This guide outlines general issues in searching for studies; describes the main sources of potential studies; and discusses how to plan the search process, design, and carry out search strategies, manage references found during the search process and document and report the search process., (© 2024 The Author(s). Campbell Systematic Reviews published by John Wiley & Sons Ltd on behalf of The Campbell Collaboration.)

Background: Embedded researchers are a novel intervention to improve the translation of research evidence into policy and practice settings, including public health. These roles are being implemented with increasing popularity, but they often lack clear evaluative frameworks. Understanding initial levels of research activity, including associated barriers and opportunities, is essential to developing theories of change and thus shaping the roles and defining expectations. We aimed to identify the principal determinants of research activity in public health that contextualise embedded researcher roles, including attributes of the embedded researcher themselves., Methods: We undertook seventeen semi-structured interviews with embedded researchers in diverse public health settings in English local government. Interviews were analysed using thematic analysis., Results: We identified thirteen interlinked determinants of research activity within local government public health settings. Research and interpersonal skills, as well as pre-existing connections and knowledge within local government, were highly valued individual attributes for embedded researchers. Resource deficiencies (funding, time, and infrastructure) were primary barriers to research activity, whereas a strong local appetite for evidence informed decision making presented a valuable opportunity. However, there was inconsistencies across public health teams relating to perceptions of what constituted "research" and the resources that would be required., Conclusions: Our results suggest that successful embedded researchers will have equally strong research and communication skills and should be offered mentorship and clear career progression pathways. Perceptions of research within local government are closely linked to resource deficiencies and senior endorsement. Embedded researchers could benefit from taking the time to develop locally contextualised knowledge of this research culture. Theories of change for embedded researchers should conceptualise the interconnections across individual, interpersonal, and organisational barriers and opportunities underlying local government research activity. Further research is needed to identify methods for exploring the influence of embedded researchers as well as to unpack the stages of research activity within local government and the associated behaviours., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

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., (© 2024. The Author(s).)

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., Competing Interests: Competing interests: Andrea Cipriani received research, educational and consultancy fees from the Italian Network for Paediatric Trials, CARIPLO Foundation, Lundbeck, and Angelini Pharma. Toshi A. Furukawa reports personal fees from Boehringer-Ingelheim, Daiichi Sankyo, DT Axis, Kyoto University Original, Shionogi, and SONY, and a grant from Shionogi outside the submitted work; in addition, TAF has patents 2020-548587 and 2022-082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. Oliver D. Howes has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Elysium, Heptares, Global Medical Education, Invicro, Jansenn, Karuna, Lundbeck, Merck, Neurocrine, Ontrack/ Pangea, Otsuka, Sunovion, Recordati, Roche, Rovi and Viatris/ Mylan. He was previously a part-time employee of Lundbeck A/v. Dr Howes has a patent for the use of dopaminergic imaging. In the last three years Stefan Leucht has received honoraria for advising/consulting and/or for lectures and/or for educational material from Angelini, Boehringer Ingelheim, Eisai, Ekademia, GedeonRichter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Mitsubishi, Otsuka, NovoNordisk, Recordati, Rovi, Teva. Robert A. McCutcheon has received speaker/consultancy fees from Karuna, Janssen, Boehringer Ingelheim, and Otsuka, and is a director of a company that hosts psychotropic prescribing decision tools. Carmen Moreno received honoraria as a consultant and/or advisor and/or for lectures from Angelini, Compass, Esteve, Exeltis Janssen, Lundbeck, Neuraxpharm, Nuvelution, Otsuka, Pfizer, Servier and Sunovion outside the submitted work. Nobuyuki Nomura has received speaker fees from Eisai, Meiji Seika Pharma, Otsuka, and Sumitomo Pharma; and manuscript fees from Sumitomo Pharma. Edoardo G. Ostinelli has received research and consultancy fees from Angelini Pharma. No other competing interests were disclosed., (Copyright: © 2024 Siafis S et al.)

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., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:This study represents independent research commissioned through the National Institute for Health and Care Research (NIHR) Policy Research Programme (PRP) for the Department of Health and Social Care (DHSC). It was funded through a supplement to the NIHR PRP contract with the EPPI Centre at UCL (Reviews facility to support national policy development and implementation, PR-R6-0113-11003). The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the DHSC. NIHR also funded the embedded researcher programme that was the focus of the research, but had no substantial input in the study design, data collection, analysis, interpretation of data, in the writing of the article, or in the decision to submit the article for publication., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: Intestinal failure [IF] is a recognised complication of Crohn's disease [CD]. The aim of this study was to identify factors predicting the development and recurrence of CD in patients with IF [CD-IF], and their long-term outcomes., Methods: This was a cohort study of adults with CD-IF admitted to a national UK IF reference centre between 2000 and 2021. Patients were followed from discharge with home parenteral nutrition [HPN] until death or February 28, 2021., Results: In all, 124 patients were included; 47 [37.9%] changed disease location and 55 [44.4%] changed disease behaviour between CD and CD-IF diagnosis, with increased upper gastrointestinal involvement [4.0% vs 22.6% patients], p <0.001. Following IF diagnosis, 29/124 [23.4%] patients commenced CD prophylactic medical therapy; 18 [62.1%] had a history of stricturing or penetrating small bowel disease; and nine [31.0%] had ileocolonic phenotype brought back into continuity. The cumulative incidence of disease recurrence was 2.4% at 1 year, 16.3% at 5 years and 27.2% at 10 years; colon-in-continuity and prophylactic treatment were associated with an increased likelihood of disease recurrence. Catheter-related bloodstream infection [CRBSI] rate was 0.32 episodes/1000 catheter days, with no association between medical therapy and CRBSI rate., Conclusions: This is the largest series reporting disease behaviour and long-term outcomes in CD-IF and the first describing prophylactic therapy use. The incidence of disease recurrence was low. Immunosuppressive therapy appears to be safe in HPN-dependent patients with no increased risk of CRBSI. The management of CD-IF needs to be tailored to the patient's surgical disease history alongside disease phenotype., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: Competing interests: Edoardo G. Ostinelli received research and consultancy fees from Angelini Pharma. Carmen Moreno received honoraria as a consultant and/or advisor and/or for lectures from Angelini, Compass, Esteve, Exeltis Janssen, Lundbeck, Neuraxpharm, Nuvelution, Otsuka, Pfizer, Servier and Sunovion outside the submitted work. Toshi A Furukawa received personal fees from Boehringer- Ingelheim, DT Axis, Kyoto University Original, Shionogi, and SONY, and a grant from Shionogi outside the submitted work; in addition, TAF has patents 2020-548587 and 2022-082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. Andrea Cipriani received research, educational and consultancy fees from the Italian Network for Paediatric Trials, CARIPLO Foundation, Lundbeck, and Angelini Pharma., (Copyright: © 2023 Ostinelli EG et al.)

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., Competing Interests: Competing interests: Spyridon Siafis: None Robert McCutcheon: RM received speaker/consultancy fees from Karuna, Janssen, Boehringer Ingelheim and Otsuka, and is director of a company that hosts psychotropic prescribing decision tools. Virginia Chiocchia: None. Edoardo G. Ostinelli: EGO has received research and consultancy fees from Angelini Pharma. Simonne Wright: None. Claire Stansfield: None. Damian Omari Juma: None. Ioannis Mantas: None. Oliver D. Howes: ODH is a part-time employee of H. Lundbeck A/S and has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Neurocrine, Otsuka, Sunovion, Rand, Recordati, Roche and Viatris/Mylan. Neither Howes or his family have holdings/a financial stake in any pharmaceutical company Grazia Rutigliano: None. Fiona Ramage: None. Francesca Tinsdeall: None. Claire Friedrich: None. Lea Milligan: None. Carmen Moreno: CM received honoraria as a consultant and/or advisor and/or for lectures from Angelini, Compass, Esteve, Exeltis Janssen, Lundbeck, Neuraxpharm, Nuvelution, Otsuka, Pfizer, Servier and Sunovion outside the submitted work. Julian H Elliott: None. James Thomas: None. Emily Sena: None. Malcolm R. MacLeod: None. Soraya Seedat: None Georgia Salanti: None. Jennifer Potts: None. Andrea Cipriani: AC received research, educational and consultancy fees from the Italian Network for Paediatric Trials, CARIPLO Foundation, Lundbeck, and Angelini Pharma. Stefan Leucht: SL has received honoraria as advisor and/or for lectures and/or for educational material from Alkermes, Angelini, Apsen, Eisai, Gedeon Richter, Janssen, Karuna, Kynexis, Lundbeck, Medichem, Medscape, Merck Sharpp and Dome, Mitshubishi, Neurotorium, NovoNordisk, Otsuka, Recordati, Roche, Rovi, Sanofi Aventis, TEVA, (Copyright: © 2023 Siafis S et al.)

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.

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., (© 2022 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.)