Prehospital transdermal glyceryl trinitrate in patients with ultra-acute presumed stroke (RIGHT-2): an ambulance-based, randomised, sham-controlled, blinded, phase 3 trial

Background High blood pressure is common in acute stroke and is a predictor of poor outcome; however, large trials of lowering blood pressure have given variable results, and the management of high blood pressure in ultra-acute stroke remains unclear. We investigated whether transdermal glyceryl trinitrate (GTN; also known as nitroglycerin), a nitric oxide donor, might improve outcome when administered very early after stroke onset. Methods We did a multicentre, paramedic-delivered, ambulance-based, prospective, randomised, sham-controlled, blinded-endpoint, phase 3 trial in adults with presumed stroke within 4 h of onset, face-arm-speech-time score of 2 or 3, and systolic blood pressure 120 mm Hg or higher. Participants were randomly assigned (1:1) to receive transdermal GTN (5 mg once daily for 4 days; the GTN group) or a similar sham dressing (the sham group) in UK based ambulances by paramedics, with treatment continued in hospital. Paramedics were unmasked to treatment, whereas participants were masked. The primary outcome was the 7-level modified Rankin Scale (mRS; a measure of functional outcome) at 90 days, assessed by central telephone follow-up with masking to treatment. Analysis was hierarchical, first in participants with a confirmed stroke or transient ischaemic attack (cohort 1), and then in all participants who were randomly assigned (intention to treat, cohort 2) according to the statistical analysis plan. This trial is registered with ISRCTN, number ISRCTN26986053. Findings Between Oct 22, 2015, and May 23, 2018, 516 paramedics from eight UK ambulance services recruited 1149 participants (n=568 in the GTN group, n=581 in the sham group). The median time to randomisation was 71 min (IQR 45–116). 597 (52%) patients had ischaemic stroke, 145 (13%) had intracerebral haemorrhage, 109 (9%) had transient ischaemic attack, and 297 (26%) had a non-stroke mimic at the final diagnosis of the index event. In the GTN group, participants’ systolic blood pressure was lowered by 5·8 mm Hg compared with the sham group (p<0·0001), and diastolic blood pressure was lowered by 2·6 mm Hg (p=0·0026) at hospital admission. We found no difference in mRS between the groups in participants with a final diagnosis of stroke or transient ischaemic stroke (cohort 1): 3 (IQR 2–5; n=420) in the GTN group versus 3 (2–5; n=408) in the sham group, adjusted common odds ratio for poor outcome 1·25 (95% CI 0·97–1·60; p=0·083); we also found no difference in mRS between all patients (cohort 2: 3 [2–5]; n=544, in the GTN group vs 3 [2–5]; n=558, in the sham group; 1·04 [0·84–1·29]; p=0·69). We found no difference in secondary outcomes, death (treatment-related deaths: 36 in the GTN group vs 23 in the sham group [p=0·091]), or serious adverse events (188 in the GTN group vs 170 in the sham group [p=0·16]) between treatment groups. Interpretation Prehospital treatment with transdermal GTN does not seem to improve functional outcome in patients with presumed stroke. It is feasible for UK paramedics to obtain consent and treat patients with stroke in the ultraacute prehospital setting. Funding British Heart Foundation

What hinders and helps academics to conduct dissemination and implementation (D&I) research in the field of nutrition and physical activity? An international perspective

BACKGROUND: Ineffective research-practice translation is a major challenge to population health improvement. This paper presents an international perspective on the barriers and facilitators associated with the uptake of and engagement in Dissemination and Implementation (D&amp;I) research in the fields of physical activity and nutrition. METHODS: A mixed methods study involving participants from the International Society for Behavioral Nutrition and Physical Activity (ISBNPA) network. Participants completed an online survey (May-July 2018) and/or participated in a focus group during the annual ISBNPA conference (June 2018). Descriptive statistics were generated for quantitative online and pre-focus group survey data. Fisher\u27s exact tests investigated associations of (i) length of time in academia, (ii) career stage and (iii) country of work, and agreement with \u27perceptions of D&amp;I\u27. Qualitative data were analysed thematically. RESULTS: In total, 141 participants responded to the survey (76% female, 21% aged 35-39&thinsp;years, 14 countries represented) and 25 participated in focus groups (n&thinsp;=&thinsp;3). Participants self-identified as having knowledge (48%), skills (53%) and experience supporting others (40%) to conduct D&amp;I research. The majority (96%) perceived D&amp;I was important, with 66% having organizational support for D&amp;I, yet only 52% reported prioritizing D&amp;I research. Perceptions of D&amp;I differed by length of time in academia, career stage and country of work. Barriers included: (i) lack of D&amp;I expertise; (ii) lack of organisational support/value for D&amp;I; (iii) embedded scientific beliefs/culture; (iv) methodological challenges with D&amp;I research; (v) funding/publishing priorities and; (vi) academic performance structures. Facilitators included: (i) increased presence/value of D&amp;I; (ii) collective advocacy; (iii) organisational support for D&amp;I; (iv) recruitment of D&amp;I scientists and; (v) restructure of academic performance models, funding/publishing criteria. CONCLUSIONS: Individual, organisational and system-wide factors hindered academics\u27 engagement with and support for D&amp;I research, which was perceived to reduce opportunities for research-practice translation. Factors were mostly consistent across countries and individual career stages/time spent in academia. Embedding D&amp;I early within academic training, and system-wide reorientation of academic performance and funding structures to promote and facilitate D&amp;I research, are some of the necessary actions to reduce the research-practice gap. Consistent with public health more broadly, these changes are long overdue in the fields of physical activity and nutrition

Adoption, implementation and sustainability of school-based physical activity and sedentary behaviour interventions in real-world settings: a systematic review

BACKGROUND: Globally, many children fail to meet the World Health Organization's physical activity and sedentary behaviour guidelines. Schools are an ideal setting to intervene, yet despite many interventions in this setting, success when delivered under real-world conditions or at scale is limited. This systematic review aims to i) identify which implementation models are used in school-based physical activity effectiveness, dissemination, and/or implementation trials, and ii) identify factors associated with the adoption, implementation and sustainability of school-based physical activity interventions in real-world settings. METHODS: The review followed PRISMA guidelines and included a systematic search of seven databases from January 1st, 2000 to July 31st, 2018: MEDLINE, EMBASE, CINAHL, SPORTDiscus, PsycINFO, CENTRAL, and ERIC. A forward citation search of included studies using Google Scholar was performed on the 21st of January 2019 including articles published until the end of 2018. Study inclusion criteria: (i) a primary outcome to increase physical activity and/or decrease sedentary behaviour among school-aged children and/or adolescents; (ii) intervention delivery within school settings, (iii) use of implementation models to plan or interpret study results; and (iv) interventions delivered under real-world conditions. EXCLUSION CRITERIA: (i) efficacy trials; (ii) studies applying or testing school-based physical activity policies, and; (iii) studies targeting special schools or pre-school and/or kindergarten aged children. RESULTS: 27 papers comprising 17 unique interventions were included. Fourteen implementation models (e.g., RE-AIM, Rogers' Diffusion of Innovations, Precede Proceed model), were applied across 27 papers. Implementation models were mostly used to interpret results (n = 9), for planning evaluation and interpreting results (n = 8), for planning evaluation (n = 6), for intervention design (n = 4), or for a combination of designing the intervention and interpreting results (n = 3). We identified 269 factors related to barriers (n = 93) and facilitators (n = 176) for the adoption (n = 7 studies), implementation (n = 14 studies) and sustainability (n = 7 studies) of interventions. CONCLUSIONS: Implementation model use was predominately centered on the interpretation of results and analyses, with few examples of use across all study phases as a planning tool and to understand results. This lack of implementation models applied may explain the limited success of interventions when delivered under real-world conditions or at scale. TRIAL REGISTRATION: PROSPERO (CRD42018099836)