Gavin Stewart

Trustworthy pain research is essential for developing a deeper understanding of the phenomena, how it is experienced, its many impacts and how it might be reduced, prevented or managed to improve the lives of those who live with pain. Recognising multiple critical challenges that undermine trust in health research, an international, interdisciplinary network was convened to create an integrated framework for enhancing the trustworthiness of research in pain. The ENTRUST-PE framework was launched in 2024 with a call to action, proposing that trustworthiness in pain research is multidimensional and underpinned by 7 Core Values: Integrity and Governance; Equity, Diversity and Inclusivity; Patient and Public Involvement and Engagement; Methodological Rigour; Openness and Transparency; Balanced Communication and Data Authenticity. The framework includes specific recommendations for a range of interest holders and resources to support those recommendations. In this paper, we summarise the framework, reflect on the response to the framework from the pain research community, consider challenges and opportunities in the evolving research landscape and suggest how we might move towards deeper implementation to enhance the trustworthiness of pain research.

Systematic reviews and meta‐analyses are key evidence synthesis methods for informing future research, interventions and policy. As the validity of their conclusions depends on the primary studies they synthesise, assessing the internal validity of the included studies is essential. In some fields, such as medicine, this is the norm and is commonly done using Risk of Bias assessment tools. Risk of Bias (RoB) assessment is however rare in ecology and evolutionary biology (EEB) even though several RoB tools have been developed in some ecological subfields and related fields. To identify potential reasons for a limited uptake, we conducted a survey of ecologists and evolutionary biologists with evidence synthesis experience and reviewed 275 journals that publish EEB research for guidelines on performing RoB or related assessments. Only 28 of 232 (12%) survey respondents had correct interpretation of the RoB concept, while 46 (40%) of 116 that had heard of RoB have confused RoB with publication bias. Just 10 (4%) had conducted a RoB assessment, most of whom found it challenging. Out of the 209 EEB journals that explicitly solicit evidence synthesis ( N = 58) or reviews ( N = 151), only five (2%) directly mentioned standards for conducting evidence synthesis, which include RoB or related (e.g. critical appraisal) assessments. An additional 45 (22%) journals indirectly linked to RoB or a related assessment via referring to the guidelines for reporting evidence synthesis (e.g. PRISMA), despite such reporting guidelines not providing information on how to conduct RoB assessments. To increase its uptake in EEB we recommend making RoB assessment: (1) known and recognised as an essential component of a reliable evidence synthesis by including it in training materials, and journals' and funders' guidelines and policies; (2) easy to perform by bringing the synthesis community together to determine the need for developing new or adjusting existing RoB tools; and (3) possible by further improving reporting standards for primary studies so that RoB assessment can be done on these studies. For those unfamiliar with the RoB assessment, we provide five key RoB questions that existing tools often cover. These questions can be considered to understand the basic composition of the evidence included in evidence synthesis.

Background: Climate change and widespread environmental degradation have increased the risk of natural hazards in recent decades. Hydrological, meteorological, and climatological disasters have become more frequent globally (Parry et al. 2007; Cavallo and Noy 2009; CRED 2022), affecting over 3.9 billion people since 2000 and causing losses totalling USD 2.2 trillion (CRED 2020). However, the greatest consequences are felt in low and middle income countries (LMICs) where nearly 90% of deaths due to natural hazards between 2000 and 2018 (World Meteorological Organization 2021). Objectives: This rapid systematic review aimed to assess and synthesise the evidence on the effects and cost-effectiveness of ecosystem disaster risk reduction (Eco-DRR) interventions in preventing and mitigating hazards and natural disasters, and consequences for natural capital and human development outcomes. Search Methods: We initially screened 529 articles from a prior review (Sudmeier-Rieux et al. 2021) on Eco-DRR interventions using a pre-validated tool in EPPI Reviewer to apply inclusion and exclusion criteria. We also identified project-level evaluations from organisations such as OECD DEReC, UNDP ERC, and the UNDRR. The search was further enhanced using machine learning in Open Alex to create a citation network, using the studies identified in the initial steps as a training dataset. Selection Criteria: This review includes empirical primary studies measuring the impacts and cost-effectiveness of Eco-DRR interventions. We searched for and included studies that evaluated primary outcomes, including hazard prevention, hazard mitigation and natural capital stocks; we also included secondary human development outcomes if reported in these papers. Eligible designs included ex-post impact evaluations using randomised assignment (randomised controlled trials [RCTs]), quasi-experimental designs (QEDs) and qualitative impact evaluation designs, and ex-ante impact evaluations using statistical modelling approaches. Economic and financial evaluations (cost-effectiveness, cost-utility and cost-benefit analyses [CBAs]) were included to measure cost- effectiveness. Data Collection and Analysis: Two reviewers were assigned to screen the title and abstract for each study. Potentially relevant studies were then assessed at full text by two independent coders, following which data collection for the included studies was double-coded. A third reviewer resolved all disagreements. All included studies were assessed using a pre-validated critical appraisal tool based on the, ‘weakest link’ principle. Findings were synthesised by grouping outcomes into hazard prevention and mitigation, natural capital, and human development outcomes. Results: The review synthesised evidence from 58 studies, of which 28 were effectiveness studies, 20 were economic evaluations, and 10 were modelling studies. The effectiveness studies were all in green infrastructure nearly all concerned forestry and natural land use interventions, primarily protected areas although one study also evaluated geophysical hazards (public investment and early warning about urban landslides). Most evaluations were of interventions in Latin America and the Caribbean (21 studies), although there was a small number in Sub-Saharan Africa (5 studies) and East Asia and the Pacific (16 studies); five evaluations were done at the global (LMICs) level. The effectiveness studies were assessed as being of moderate confidence (6 studies) or low confidence (21 studies). The synthesis of outcomes, using meta-analysis of effect sizes ( g ), found beneficial effects of Eco-DRR interventions on hazard incidence and exposure and natural capital outcomes. These included large effects on the reduction of forest fire ( g = 0.32; 95% confidence interval (CI) = 0.23, 0.48; evidence from 4 studies), and medium- and small-sized beneficial effects on forest cover ( g = 0.12; 95% CI = 0.07, 0.18; 16 studies) and vegetation cover ( g = 0.06; 95% CI = 0.01, 0.11; 4 studies). The synthesis of secondary human development outcomes was more limited because only a small subset (3) of papers that primarily measured hazard exposure and natural capital also reported these outcomes, which included loss of life, property damage, income, expenditure, and agricultural revenues. There were 10 modelling papers, of which half were for countries in Latin America and the Caribbean, 4 from East Asia, and 1 for South Asia. Five of the papers were concerned exclusively with flooding, two concerned storm surges (and thus also with flooding), and two more included flooding among the hazards assessed. One paper concerned landslides. Each paper used a different model and reported different outcomes. All papers used a range of different data sources, including satellite data, existing meteorological and other data sources, and primary data collection by the study team. None of the papers reported economic analysis. Two of the 10 papers were rated as high confidence in study findings, 5 at moderate confidence, and 3 at low confidence. Twenty economic evaluations assessing the cost-effectiveness of Eco-DRR measures were included. All the included papers were CBAs, with two papers accounting for income differences and incorporating equity weights to estimate social welfare benefits. While direct costs for structural measures were widely included, indirect costs and benefits were rarely reported. These indirect costs include the loss of productivity due to evacuations, repairs, and disruptions to economic activity. Similarly, the benefits of non-structural measures, such as reduced flood damage and avoided societal disruptions, are often difficult to quantify and not reported. Five of the 20 papers were rated as having high confidence in the study findings, 8 were at moderate confidence and the 7 were at low confidence. Most results support the economic effectiveness of Eco-DRR interventions. BCRs of 4 and above were regularly reported. For example, an extremely high BCR of 1800 was reported for drought risk reduction measures in Sudan for irrigation, early warning systems demonstrating exceptionally high potential financial returns (IRR of 409%). Additionally, the ecological prioritisation of engineering measures was lower compared to EbA measures, as they were primarily focused on addressing water scarcity without the same level of positive ecological impacts. Conclusion: The evidence base on the effectiveness and cost-effectiveness of Eco-DRR is compartmentalised. Most studies of the effectiveness of implemented actions have evaluated green infrastructure interventions, particularly protected areas, whereas most of the modelling and cost-effectiveness studies evaluated blue and hybrid infrastructure technologies. Green infrastructure interventions, such as protected areas, have generally shown large effects on increasing natural capital stocks, especially in forestry reserves, and on reducing the incidence of or exposure to hazards like fire, although fewer studies have measured the latter. In modelling studies, most of the papers concluded that the intervention being assessed should be adopted. But in the absence of economic analysis, such a conclusion cannot be drawn from the demonstrated impact alone. Economic evaluations generally supported the benefits exceeding costs (BCRs > 1) of Eco-DRR, particularly in reducing flooding, especially structural hybrid interventions, but also capacity building, early warning systems, and mangrove restoration. However, these studies have significant limitations regarding information about distributional effects, non-monetised values, and indirect costs and benefits. Interventions with the highest BCRs included early warning systems for floods and non-structural interventions, such as land use planning and capacity building. Future economic evaluations should be more comprehensive, considering direct and indirect costs and benefits. Improvements in understanding different approaches to Eco-DRR and the relative role of directly targeted versus systemic approaches to risk management are essential. We found very limited research on environmental hazards and geological and geophysical hazards, such as landslides and earthquakes, suggesting that these topics require investigation in LMICs in future primary studies of whatever type (both effectiveness and cost-effectiveness). More studies that evaluate topics relating to equity, such as the effects on the social welfare of vulnerable populations, are needed. Studies of the effectiveness in these areas might usefully draw on established methods of qualitative impact evaluation. (Summary of findings tables: S1).

Background: Chronic pain is common and costly. Antidepressants are prescribed to reduce pain. However, there has not been a network meta-analysis examining all antidepressants across all chronic pain conditions, so effectiveness and safety for most antidepressants for pain conditions remain unknown. Objective: To assess the efficacy and safety of antidepressants for chronic pain (except headache) in adults. Our primary outcomes were as follows: substantial pain relief (50%), pain intensity, mood and adverse events. Our secondary outcomes were as follows: moderate pain relief (30%), physical function, sleep, quality of life, Patient Global Impression of Change, serious adverse events and withdrawal. Design: This was a systematic review with a network meta-analysis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, AMED and PsycINFO databases for randomised controlled trials of antidepressants for chronic pain conditions up until 4 January 2022. The review was registered in PROSPERO (CRD42020171855), and the protocol was published in the Cochrane Library (https://doi.org/10.1002/14651858.CD014682). Setting: We analysed trials from all settings. Participants: We included trials in which participants had chronic pain, defined as longer than 3 months, from any condition excluding headache. Interventions: We included all antidepressants. Main outcome measures: Our primary outcome was substantial pain relief, defined as a reduction ˃ 50%. We also measured pain intensity, mood and adverse events. Secondary measures included moderate pain relief (above 30% reduction), physical function, sleep, quality of life, Global Impression of Change, serious adverse events, and withdrawal from trial. Results: We identified 176 studies with a total of 28,664 participants. Most studies were placebo-controlled (n = 83) and parallel armed (n = 141). The most common pain conditions examined were fibromyalgia (59 studies), neuropathic pain (49 studies) and musculoskeletal pain (40 studies). The average length of randomised controlled trials was 10 weeks. Most studies measured short-term outcomes only and excluded people with low mood and other mental health conditions. Across efficacy outcomes, duloxetine was consistently the highest-ranked antidepressant with moderate- to high-certainty evidence. Standard dose was equally efficacious as high dose for the majority of outcomes. Milnacipran was often ranked as the next most efficacious antidepressant, although the certainty of evidence was lower than that for duloxetine. There was insufficient evidence to draw robust conclusions for the efficacy and safety of any other antidepressant for chronic pain. Limitations: The evidence for antidepressants other than duloxetine is poor. For duloxetine, it is not clear whether the effect applies to groups with both pain and low mood, since these groups were excluded from trials. There is also insufficient evidence on long-term outcomes and on adverse effects. Conclusions: There is only reliable evidence for duloxetine in the treatment of chronic pain. Duloxetine was moderately efficacious across all outcomes at standard dose. There is also promising evidence for milnacipran, although further high-quality research is needed to be confident in these conclusions. Data for all other antidepressants were of low certainty. However, the findings should not be read as an encouragement to prescribe antidepressants where other non-pharmacological intervention could be equally effective, especially in the absence of good evidence on side effects and safety. Future work: There is a need for large, methodologically sound trials testing the effectiveness of antidepressants for chronic pain. These trials should examine long-term outcomes (> 6 months) and include people with low mood. There should also be better reporting of adverse events, tolerance of drugs, and long-term compliance. Study registration: This study is registered as PROSPERO CRD42020171855. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128782) and is published in full in Health Technology Assessment; Vol. 28, No. 62. See the NIHR Funding and Awards website for further award information.

Nitrogen fertilisation is a common form of agricultural intensification, aimed at increasing biomass, which can affect plant species diversity and ecosystem functioning. Using a systematic review and meta-analysis of nitrogen fertilisation studies in European permanent grasslands, we asked: (i) what relationship form exists between nitrogen application rate and change in plant diversity, compared to zero fertilisation controls; and (ii) how grassland, management and study characteristics affect this relationship. Meta-analysis of 34 control-treatment effects from 14 studies conducted across nine European countries revealed a negative linear relationship between nitrogen fertilisation rate and change in plant species richness, equivalent to approximately 1.5 species/m² lost for every 100 Kg ha⁻¹ yr⁻¹ of nitrogen added. Fertilisation induced reductions in plant species richness were greater when defoliation rates were lower. We found some evidence that grasslands with a higher baseline plant diversity lost more species when fertilised compared to more species poor grasslands, although uncertainty was high. Due to the diverse grassland types included in the analysis, the variability in fertilisation-driven changes in plant diversity was high. We identified several remaining limitations to our understanding, including uncertainty about non-linear effects, which could aid efforts to optimise the trade-off of plant diversity and increasing grassland yields.

Participation is increasingly used to legitimize and improve environmental decision making. However, in practice participants often find the process empty and frustrating. This has adverse consequences for environmental planning and consenting processes, where participants become disillusioned, and negative feelings develop into active opposition, causing delays, spiraling costs, and conflict. This paper addresses the gap between participatory ideals and unsatisfactory environmental decision-making in practice. We take a fresh look at how participatory ideals can be implemented and propose a new framework based on translating participatory ideals into practice. We identified commitments and values for fair and achievable participatory environmental decision-making from science and technology studies (STS), procedural environmental justice, and deliberative democracy. These were synthesized and organized into a set of principles (inclusivity, process-orientation, empowerment, and reflection) and then translated into “practical” criteria. The result is a new framework that links participatory ideals to practice.