“Interest-holders”: A new term to replace “stakeholders” in the context of health research and policy

BackgroundGiven the colonial connotations of the term “stakeholder”, its continued use may be perceived as disrespectful to Indigenous Peoples. While several groups have introduced alternative terms, each has its own limitations. The objective of this article is to introduce “interest-holders” as an alternative term to “stakeholders” and describe the discussions underpinning the adoption of the new term by the MuSE Consortium.MethodsThe MuSE Consortium is an international network of over 160 individuals with interest and expertise in different aspects relevant to engagement in research. Members of MuSE explored alternative terms and considered their respective merits and limitations. The deliberations considered the literature on the topic and the results of two consultations with the wider MuSE membership on the alternative terms.ResultsWe define “interest-holders” as groups with legitimate interests in the health issue under consideration. The interests arise and draw their legitimacy from the fact that people from these groups are responsible for or affected by health-related decisions that can be informed by research evidence.ConclusionAs groups other than the MuSE Consortium have started to adopt “interest-holders,” we hope its use will reduce confusion related to the multitude of terms used and convey the intended meaning without any negative connotations

The effects of exercise on secondary prevention and health-related quality of life in people with existing vascular disease: systematic review and meta-analysis of randomised controlled trials

\ua9 2025 The AuthorsBackground: Polyvascular disease (atherosclerosis across two or more vascular beds) is becoming increasingly common, yet systematic reviews of interventions such as exercise are traditionally targeted at people with a single disease. We aimed to determine the effect of exercise in the secondary prevention of major adverse cardiovascular events and health-related quality of life (HRQoL) in people with an existing vascular disease and to assess the impact of polyvascular disease. Methods: For this systematic review and meta-analysis, we searched databases (Cochrane Register of Studies Online, MEDLINE, Embase Ovid, CINAHL EBSCO, WHO-ICTRP and ClinicalTrials.gov) in January 2025 for randomised controlled trials (RCTs) of exercise in people with coronary artery disease, heart failure, stroke (including transient ischaemic attack (TIA)) and peripheral arterial disease (PAD). We excluded studies where exercise was delivered for <6 weeks. Two reviewers independently assessed articles for eligibility and extracted data. Disagreements were resolved through discussion. Critical outcomes were mortality (all-cause and cardiovascular-specific), vascular events (myocardial infarction, stroke, amputation, acute limb ischaemia (ALI)), vascular hospitalisations, and HRQoL (EQ-5D and SF-36). We extracted data at end of intervention, medium term (6–30 months follow-up), and long term (>30 months follow-up). We performed random-effects meta-analyses. Risk of bias was assessed using Cochrane\u27s Risk of Bias 1 tool. The certainty of the evidence was assessed using GRADE. PROSPERO registration: CRD42024517019. Findings: We included 280 RCTs involving 23,419 participants. 114 (40\ub771%) studies did not report whether their populations had more than one vascular disease. Exercise may result in little to no difference in all-cause mortality compared to no exercise at end of intervention (risk ratio (RR) 0\ub792, 95% confidence interval (CI) 0\ub780–1\ub707; P = 0\ub730; 143 studies, 12,811 participants; low-certainty evidence). Similar effects were found at medium and long term. Exercise may result in little to no difference in cardiovascular mortality compared to no exercise at end of intervention (RR 0\ub792, 95% CI 0\ub775–1\ub712; P = 0\ub741; 77 studies, 7319 participants; low-certainty evidence). A similar effect was found at medium term. At long term there may be a difference favouring exercise on cardiovascular mortality (RR 0\ub781, 95% CI 0\ub764–1\ub701; P = 0\ub706; 10 studies, 3935 participants). Exercise probably reduces vascular hospitalisations compared to no exercise at end of intervention (RR 0\ub773, 95% CI 0\ub756–0\ub795; P = 0\ub702; 64 studies, 7101 participants; moderate-certainty evidence) and medium term (RR 0\ub783, 95% CI 0\ub770–0\ub799; P = 0\ub704; 49 studies, 7514 participants; low-certainty evidence), with little or no difference at long term. Exercise probably increases HRQoL as assessed by EQ-5D compared to no exercise at end of intervention (mean difference (MD), 6\ub720, 95% CI 2\ub721–10\ub720; P = 0\ub7002; 8 studies, 805 participants; moderate-certainty evidence), with little or no difference at medium term (MD 2\ub723, 95% CI –3\ub719 to 7\ub766; P = 0\ub742; 7 studies, 707 participants; moderate-certainty evidence) and long term (MD 6\ub700, 95% CI –2\ub705 to 14\ub705; P = 0\ub714; 1 study, 73 participants). Exercise probably increases HRQoL as assessed by SF-36 compared to no exercise at end of intervention (MD 6\ub783, 95% CI 5\ub722–8\ub744; P < 0\ub70001; 50 studies, 3231 participants; moderate-certainty evidence) and medium term (MD 6\ub744, 95% CI 3\ub771–9\ub718; P < 0\ub70001; 15 studies, 1522 participants; moderate-certainty evidence). No studies reported SF-36 at long term. Data on vascular events were mixed and of low certainty. Evidence was limited, and therefore uncertain, for amputation and ALI. Limiting issues were poor descriptions of exercise, and poor, inconsistently reported study inclusion and exclusion criteria, therefore limiting our ability to categorise included populations as polyvascular/single. Interpretation: We believe this systematic review and meta-analysis to be the first to combine RCTs with vascular diseases and examine the effects of exercise in people with single conditions and polyvascular disease. We found consistent evidence that exercise improves HRQoL and reduces hospitalisations across vascular disease but does not appear to impact mortality. However, the vast majority of trials were designed to target people with a single vascular condition and did not report the presence of additional vascular diseases. Therefore, it was not possible to formally assess the impact of the addition of polyvascular disease on exercise outcomes or determine the applicability of our findings to a population with polyvascular disease. More trials are needed that include participants with polyvascular conditions to strengthen the evidence on safety of this intervention, in order to inform clinical guidelines. Funding: This study was funded by the NIHR Evidence Synthesis Programme (NIHR162044)

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes

The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1924 diabetic cases and 2938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3757 additional cases and 5346 controls and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibility loci in and around the genes CDKAL1, CDKN2A/CDKN2B, and IGF2BP2 and confirmed the recently described associations at HHEX/IDE and SLC30A8. Our findings provide insight into the genetic architecture of type 2 diabetes, emphasizing the contribution of multiple variants of modest effect. The regions identified underscore the importance of pathways influencing pancreatic beta cell development and function in the etiology of type 2 diabetes.</p

Interventions for improving walking after stroke: an overview of Cochrane Reviews (Protocol)

Objectives: This is a protocol for a Cochrane Review (overview). The objectives are as follows:. To summarise and appraise the evidence from Cochrane Reviews assessing the effects of interventions for the recovery and/or the improvement of walking in people after stroke. We will conduct an overview of Cochrane Reviews involving stakeholders to:. provide accessible high-quality evidence on the effects of interventions aiming to recover and/or improve walking in people after stroke; summarise the evidence of the effects of included interventions; clearly present to readers relevant, high-quality evidence of effective interventions; and direct them to original reviews. A secondary objective will be to explore the outcomes reported in Cochrane Reviews assessing the effects of interventions to improve walking; how different measures are combined in reviews; and how this varies between reviews

In vitro activity of cadazolid against clinically relevant Clostridium difficile isolates and in an in vitro gut model of C. difficile infection

Abstract Objectives We investigated the in vitro activity of cadazolid against 100 Clostridium difficile isolates and its efficacy in a simulated human gut model of C. difficile infection (CDI). Methods MICs of cadazolid, metronidazole, vancomycin, moxifloxacin and linezolid were determined using agar incorporation for 100 C. difficile isolates, including 30 epidemic strains (ribotypes 027, 106 and 001) with reduced metronidazole susceptibility, 2 linezolid-resistant isolates and 2 moxifloxacin-resistant isolates. We evaluated the efficacy of two cadazolid dosing regimens (250 versus 750 mg/L twice daily for 7 days) to treat simulated CDI. Microflora populations, C. difficile total viable counts and spores, cytotoxin titres, possible emergence of cadazolid, linezolid or quinolone resistance, and antimicrobial concentrations were monitored throughout. Results Cadazolid was active against all (including linezolid- and moxifloxacin-resistant) C. difficile strains (MIC90 0.125, range 0.03–0.25 mg/L). The cadazolid geometric mean MIC was 152-fold, 16-fold, 9-fold and 7-fold lower than those of moxifloxacin, linezolid, metronidazole and vancomycin, respectively. Both cadazolid dosing regimens rapidly reduced C. difficile viable counts and cytotoxin with no evidence of recurrence. Cadazolid levels persisted at 50–100-fold supra-MIC for 14 days post-dosing. Cadazolid inhibition of enumerated gut microflora was limited, with the exception of bifidobacteria; Bacteroides fragilis group and Lactobacillus spp. counts were unaffected. There was no evidence for selection of strains resistant to cadazolid, quinolones or linezolid. Conclusions Cadazolid activity was greater than other tested antimicrobials against 100 C. difficile strains. Cadazolid effectively treated simulated CDI in a gut model, with limited impact on the enumerated gut microflora and no signs of recurrence or emergence of resistance within the experimental timeframe.Peer reviewe

Guidance for engagement in health guideline development: A scoping review

Abstract Background Health guideline developers engage with interested people and groups to ensure that guidelines and their recommendations are relevant and useful to those who will be affected by them. These ‘interest‐holders’ include patients, payers/purchasers of health services, payers of health research, peer review editors, product makers, programme managers, policymakers, providers, principal investigators, and the public. The Guidelines International Network (GIN) and McMaster University Guideline Development Checklist describes 146 steps of the guideline process organized into 18 topics. While one topic focuses on engagement, it does not describe how to engage with interest‐holders. In addition, interest‐holder input could be sought throughout the guideline development process. This scoping review is part of a series of four related reviews. The three other reviews address barriers and facilitators to engagement in guideline development, managing conflicts of interest in guideline development, and assessing the impact of interest‐holder engagement on guideline development. The four reviews will inform the development of guidance for multi‐interest‐holder engagement in guideline development; the GIN‐McMaster Guideline Development Checklist Extension for Engagement. Objectives The objective of this scoping review is to identify, describe, and summarise existing guidance and methods for multi‐interest‐holder engagement throughout the health guideline development process. Search Methods We conducted one comprehensive search for studies of engagement in guidelines to meet the inclusion criteria of one or more of the four systematic reviews in this series. We searched MEDLINE (OVID), CINAHL (EBSCO), EMBASE (OVID), PsycInfo (OVID) and SCOPUS databases up to September 2022. We did not include limits for date, study design, or language. We searched websites of agencies and organizations that engage interest‐holder groups, such as the Agency for Healthcare Research and Quality (AHRQ), CIHR Strategy for Patient‐Oriented Research (SPOR), National Institute for Health and Care Research (NIHR) Be Part of Research, Guidelines International Network (G‐I‐N), the National Institute for Health and Care Excellence, and the PatientCentred Outcomes Research Institute (PCORI). We handsearched the websites of guideline producing agencies. We solicited additional grey literature from the members of the MuSE Consortium. Selection Criteria Studies were included in this review if they reported on engagement of any of our identified groups, patients, payers/funders of research, payers/purchasers of health services, policymakers, programme managers, providers, principal investigators/researchers, peer review editors, product makers in the development of a health guideline. Titles and abstracts of identified citations were screened independently, in duplicate. The full text of potentially relevant papers were screened for eligibility into one or more of the four reviews in the series. Screening was done independently, by two reviewers. The team held weekly meetings with all reviewers involved in screening to discuss and resolve conflicts. Data Collection and Analysis Two reviewers extracted relevant data into a pilot‐tested data extraction form using Excel. We used the GIN‐McMaster guideline development checklist as a framework for extracting the available guidance for each of our identified interest‐holder groups throughout the development process. We presented descriptive statistics of the number of papers reporting guidance for each groups across the steps of the guideline process. We synthesized the relevant text using a qualitative meta‐summary approach. Main Results We included 16 papers (from 17 reports). These papers were from Australia, Denmark, the Netherlands, the UK, and the USA, and eight papers were international (countries not specified). The papers provided guidance for at least one of our interest‐holder groups for at least one stage of guideline development. We mapped this guidance to the GIN‐McMaster Guideline Development Checklist to identify the available guidance for each of our interest‐holder groups across all stages of the guideline development process. Guidance was available for patient engagement in 15 of the 16 papers. At least two papers provided guidance for each of the 18 topics of the GIN‐McMaster Guideline Development Checklist. For healthcare providers, 9 papers provided guidance for their engagement across 10 of the 18 guideline development topics. Guidance for engaging with the public was provided for 14 of the 18 topics and reported in 4 of our included papers. For payers/purchasers of health services, policymakers, product makers, programme managers, and principal investigators, 2–3 papers provided guidance for these groups across 4–7 topics of the GIN‐McMaster checklist. We did not identify any specific guidance for payers of health research or for editors of peer‐reviewed journals. Authors' Conclusions Guidance for interst‐holder engagement in guidelines is available but has focused primarily on patients. We will utilize the guidance identified in this scoping review to inform the GIN‐McMaster Guideline Development Checklist Extension for engagement. Combined with the information obtained from the other systematic reviews in this series, we will address the gaps in guidance for the other identified interest‐holder groups