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Background Adrenaline has been used as a treatment for cardiac arrest for many years, despite uncertainty about its effects on long-term outcomes and concerns that it may cause worse neurological outcomes. Objectives The objectives were to evaluate the effects of adrenaline on survival and neurological outcomes, and to assess the cost-effectiveness of adrenaline use. Design This was a pragmatic, randomised, allocation-concealed, placebo-controlled, parallel-group superiority trial and economic evaluation. Costs are expressed in Great British pounds and reported in 2016/17 prices. Setting This trial was set in five NHS ambulance services in England and Wales. Participants Adults treated for an out-of-hospital cardiac arrest were included. Patients were ineligible if they were pregnant, if they were aged Interventions Participants were randomised to either adrenaline (1 mg) or placebo in a 1 : 1 allocation ratio by the opening of allocation-concealed treatment packs. Main outcome measures The primary outcome was survival to 30 days. The secondary outcomes were survival to hospital admission, survival to hospital discharge, survival at 3, 6 and 12 months, neurological outcomes and health-related quality of life through to 6 months. The economic evaluation assessed the incremental cost per quality-adjusted life-year gained from the perspective of the NHS and Personal Social Services. Participants, clinical teams and those assessing patient outcomes were masked to the treatment allocation. Results From December 2014 to October 2017, 8014 participants were assigned to the adrenaline (n = 4015) or to the placebo (n = 3999) arm. At 30 days, 130 out of 4012 participants (3.2%) in the adrenaline arm and 94 out of 3995 (2.4%) in the placebo arm were alive (adjusted odds ratio for survival 1.47, 95% confidence interval 1.09 to 1.97). For secondary outcomes, survival to hospital admission was higher for those receiving adrenaline than for those receiving placebo (23.6% vs. 8.0%; adjusted odds ratio 3.83, 95% confidence interval 3.30 to 4.43). The rate of favourable neurological outcome at hospital discharge was not significantly different between the arms (2.2% vs. 1.9%; adjusted odds ratio 1.19, 95% confidence interval 0.85 to 1.68). The pattern of improved survival but no significant improvement in neurological outcomes continued through to 6 months. By 12 months, survival in the adrenaline arm was 2.7%, compared with 2.0% in the placebo arm (adjusted odds ratio 1.38, 95% confidence interval 1.00 to 1.92). An adjusted subgroup analysis did not identify significant interactions. The incremental cost-effectiveness ratio for adrenaline was estimated at £1,693,003 per quality-adjusted life-year gained over the first 6 months after the cardiac arrest event and £81,070 per quality-adjusted life-year gained over the lifetime of survivors. Additional economic analyses estimated incremental cost-effectiveness ratios for adrenaline at £982,880 per percentage point increase in overall survival and £377,232 per percentage point increase in neurological outcomes over the first 6 months after the cardiac arrest. Limitations The estimate for survival with a favourable neurological outcome is imprecise because of the small numbers of patients surviving with a good outcome. Conclusions Adrenaline improved long-term survival, but there was no evidence that it significantly improved neurological outcomes. The incremental cost-effectiveness ratio per quality-adjusted life-year exceeds the threshold of £20,000–30,000 per quality-adjusted life-year usually supported by the NHS. Future work Further research is required to better understand patients’ preferences in relation to survival and neurological outcomes after out-of-hospital cardiac arrest and to aid interpretation of the trial findings from a patient and public perspective. Trial registration Current Controlled Trials ISRCTN73485024 and EudraCT 2014-000792-11. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 25. See the NIHR Journals Library website for further project information.

The history of British art abounds with an interest in the environmental, especially landscape paintings that embody the pastoral and the rural, cloud studies, and stormy skies. John Barrell’s Dark Side of the Landscape published forty years ago, convincingly argued that landscape paintings that we interpret almost immediately as idyllic, in fact emerge “from a world of social and economic relations that are anything but idyllic”. Writing about Gainsborough and Constable, among others, Barrell’s leftist critique of the English pastoral (following E.P. Thompson) urged viewers to see in the harmony that pastoral painting propagated between human and non-human, land and labour, the “evidence of the very conflict it seems to deny”. Beyond the English working class, the discipline of art history, especially British art history, is a product of the nineteenth century and thoroughly entangled with histories of colonialism and capitalism—and slavery. The art critic, John Ruskin’s interest in the geological sciences and his mineralogical collection used to teach design aesthetics, architecture, and geology is well known. In Modern Painters (1843–1860), Ruskin pressed artists to study geology. According to Ruskin, landscape possessed “vital truth” by which it simultaneously conveyed the past, the present, and the future. Metal mining in the UK and in the colonies were at its peak when Ruskin was writing. Kathryn Yusoff has recently updated what Ruskin called the “truth of the earth” by showing us how geology (and its fossil objects) is entwined with processes of racialization through speciation and notions of progress, and how it is a mode in which racial logics have been inscribed within the material politics of extraction, continuing to constitute lived forms of racism (from eugenics to environmental racism). Making the link between spatial dispossession of land (for extraction) and dispossessions of persons in chattel slavery (as another form of spatial extraction), Yusoff has argued that geology is historically situated as a transactional zone, in which mineral-as-property and person-as-property were one and the same. Conversations with the literary and gender studies scholar Katherine McKittrick have also taught me to think about how a direct line between the race thinking of slavery and our contemporary environmental predicament can end up mistreating the complexity of Black time by obscuring Black time. In privileging non-personhood as an origin story, we run the risk of undermining histories of rebellion, multiplicity, and Black life.

The ‘Great Repeal Bill’ was designed to bring all existing European Union (EU) law into UK law at the point of the country’s departure from the EU on 29th March 2019. At this time a so called ‘Hard Brexit’, with no agreement and a reversion to World Trade Organisation (WTO) trade tariffs is still possible. The Government White Paper on the future relationship with the EU of July 2018 seems however, to outline a softer Brexit or even a ‘BRINO’ (Brexit in Name Only) much to the disgust of arch-Brexiteers. One of the unprecedented number of amendments to the Bill in Parliament produced a media and social media storm on its own. This was the consideration of the concept of ‘animal sentience’ as it exists in EU law. Commentators were concerned that the vote against alignment with this was a signal that the UK Parliament was not prepared to recognise the concept at all after March 2019. Ministerial Guidance was issued within days which attempted to refute his position. Michael Gove, Environment Secretary and prominent Euro-sceptic appeared on national radio to emphasise the Government’s commitment to animal welfare and to urge the people to trust the domestic democratic process to surpass the standards that the EU has mandated in this sector. This paper sets out to consider whether this trust is warranted, specifically in the context of domesticated horses in the UK. It explores the current position and compares it to other jurisdictions, most notably the US, Canada and New Zealand. This is to analyse how willing the UK legislature has been to acknowledge animal sentience to date, as an indicator of future performance outside the constraints of EU law. The reason for narrowing the focus to equines is that we have a ‘special relationship’ with the species which has been the result of a process spanning thousands of years. This connection has shifted from one that provided more or less mutual benefits into one of absolute dependence on humankind. That said, the 21st century has seen the domestic horse take on a new and by no means less significant role within our modern lives. This is not because they continue to be used as beasts of burden, but instead have entered the realms of becoming almost quasi human, through our own changing social constructs. Cultural and societal influences through such mediums as the entertainment industry, commerce, advancements in technology and the media have placed the domestic horse well and truly at the heart of our society. Legal protection for any domesticated reached a pinnacle in 2006 with the Animal Welfare Act. This paper argues that the recognition of animals as sentient beings by both the scientific and legal worlds means that their level of legal protection should be reflected within our current law. This paper takes issue with the construction of legislation such as the Animal Welfare Act and argues that there have been missed opportunities to protect horses with rights that are more in tune with the modern social construction of horses. The paper concludes with a view, based on previous progress, as to whether the UK legislature can indeed be trusted to properly recognise animal sentience post ‘Brexit’.

This article details how the authors, two educators with doctoral degrees, attempt to harmonize their researcher and educator identities and seek to empower their students and fellow teachers as researchers. They describe how their doctoral programs influenced their beliefs about the power of a researcher identity, and they suggest ways educational institutions can support teachers and students in the development of a research mindset.

Background:\ud The PARAMEDIC cluster randomised trial evaluated the LUCAS mechanical chest compression device, and did not find evidence that use of mechanical chest compression led to an improvement in survival at 30 days. This paper reports patient outcomes from admission to hospital to 12 months after randomisation.\ud \ud Methods:\ud Information about hospital length of stay and intensive care management was obtained through linkage with Hospital Episode Statistics and the Intensive Care National Audit and Research Centre. Patients surviving to hospital discharge were approached to complete questionnaires (SF-12v2, EQ-5D, MMSE, HADS and PTSD-CL) at 90 days and 12 months. The study is registered with Current Controlled Trials, number ISRCTN08233942.\ud \ud Results:\ud 377 patients in the LUCAS arm and 658 patients in the manual chest compression were admitted to hospital. Hospital and intensive care length of stay were similar. Long term follow-up assessments were limited by poor response rates (53.7% at 3 months and 55.6% at 12 months). Follow-up rates were lower in those with worse neurological function. Among respondents, long term health related quality of life outcomes and emotional well-being was similar between groups. Cognitive function, measured by MMSE, was marginally lower in the LUCAS arm mean 26.9 (SD 3.7) compared to control mean 28.0 (SD 2.3), adjusted mean difference −1.5 (95% CI −2.6 to −0.4).\ud \ud Conclusion:\ud There were no clinically important differences identified in outcomes at long term follow-up between those allocated to the mechanical chest compression compared to those receiving manual chest compression.

BackgroundMechanical chest compression devices may help to maintain high-quality cardiopulmonary resuscitation (CPR), but little evidence exists for their effectiveness. We evaluated whether or not the introduction of Lund University Cardiopulmonary Assistance System-2 (LUCAS-2; Jolife AB, Lund, Sweden) mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest (OHCA).ObjectiveEvaluation of the LUCAS-2 device as a routine ambulance service treatment for OHCA.DesignPragmatic, cluster randomised trial including adults with non-traumatic OHCA. Ambulance dispatch staff and those collecting the primary outcome were blind to treatment allocation. Blinding of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. We also conducted a health economic evaluation and a systematic review of all trials of out-of-hospital mechanical chest compression.SettingFour UK ambulance services (West Midlands, North East England, Wales and South Central), comprising 91 urban and semiurban ambulance stations. Clusters were ambulance service vehicles, which were randomly assigned (approximately 1 : 2) to the LUCAS-2 device or manual CPR.ParticipantsPatients were included if they were in cardiac arrest in the out-of-hospital environment. Exclusions were patients with cardiac arrest as a result of trauma, with known or clinically apparent pregnancy, or aged InterventionsPatients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene.Main outcome measuresSurvival at 30 days following cardiac arrest; survival without significant neurological impairment [Cerebral Performance Category (CPC) score of 1 or 2].ResultsWe enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 device and 2819 assigned to control) between 15 April 2010 and 10 June 2013. A total of 985 (60%) patients in the LUCAS-2 group received mechanical chest compression and 11 (LimitationsThere was substantial non-compliance in the LUCAS-2 arm. For 272 out of 1652 patients (16.5%), mechanical chest compression was not used for reasons that would not occur in clinical practice. We addressed this issue by using complier average causal effect analyses. We attempted to measure CPR quality during the resuscitation attempts of trial participants, but were unable to do so.ConclusionsThere was no evidence of improvement in 30-day survival with LUCAS-2 compared with manual compressions. Our systematic review of recent randomised trials did not suggest that survival or survival without significant disability may be improved by the use of mechanical chest compression.Future workThe use of mechanical chest compression for in-hospital cardiac arrest, and in specific circumstances (e.g. transport), has not yet been evaluated.TriaI registrationCurrent Controlled Trials ISRCTN08233942.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 21, No. 11. See the NIHR Journals Library website for further project information.

Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest.This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant.8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes).Trial registration (ISRCTN73485024).

Background There is an urgent need to develop prehospital research capability in order to improve the care of patients presenting to emergency medical services (EMS). The Prehospital Randomised Assessment of a Mechanical compression Device In Cardiac arrest trial, a pragmatic cluster randomised trial evaluating the LUCAS-2 device, represents the largest randomised controlled trial conducted by UK ambulance services to date. The aim of this study was to identify and analyse factors that may influence paramedic attitudes to, and participation in, clinical trials. Methods Personal and organisational experience from this trial was assessed by feedback from a workshop attended by collaborators from participating EMS and a survey of EMS personnel participating in the trial. A work systems model was used to explain the impact of five interwoven themes—person, organisation, tasks, tools & technology and environment—on trial conduct including gathering of high-quality data. Results The challenge of training a geographically diverse EMS workforce required development of multiple educational solutions. In order to operationalise the trial protocol, internal organisational relationships were perceived as essential. Staff perceptions of the normalisation of participation and ownership of the trial influenced protocol compliance rates. Undertaking research was considered less burdensome when additional tasks were minimised and more difficult when equipment was unavailable. The prehospital environment presents practical challenges for undertaking clinical trials, but our experience suggests these are not insurmountable and should not preclude conducting high-quality research in this setting. Conclusions Application of a human factors model to the implementation of a clinical trial protocol has improved understanding of the work system, which can inform the future conduct of clinical trials and foster a research culture within UK ambulance services. Trial registration number ISRCTN08233942.

BACKGROUND: Mechanical chest compression devices have the potential to help maintain high-quality cardiopulmonary resuscitation (CPR), but despite their increasing use, little evidence exists for their effectiveness. We aimed to study whether the introduction of LUCAS-2 mechanical CPR into front-line emergency response vehicles would improve survival from out-of-hospital cardiac arrest. METHODS: The pre-hospital randomised assessment of a mechanical compression device in cardiac arrest (PARAMEDIC) trial was a pragmatic, cluster-randomised open-label trial including adults with non-traumatic, out-of-hospital cardiac arrest from four UK Ambulance Services (West Midlands, North East England, Wales, South Central). 91 urban and semi-urban ambulance stations were selected for participation. Clusters were ambulance service vehicles, which were randomly assigned (1:2) to LUCAS-2 or manual CPR. Patients received LUCAS-2 mechanical chest compression or manual chest compressions according to the first trial vehicle to arrive on scene. The primary outcome was survival at 30 days following cardiac arrest and was analysed by intention to treat. Ambulance dispatch staff and those collecting the primary outcome were masked to treatment allocation. Masking of the ambulance staff who delivered the interventions and reported initial response to treatment was not possible. The study is registered with Current Controlled Trials, number ISRCTN08233942. FINDINGS: We enrolled 4471 eligible patients (1652 assigned to the LUCAS-2 group, 2819 assigned to the control group) between April 15, 2010 and June 10, 2013. 985 (60%) patients in the LUCAS-2 group received mechanical chest compression, and 11 (

During the Protection era, Aboriginal people in Victoria frequently corresponded with colonial and state authorities. Aboriginal letter writers sometimes supported and sometimes opposed the Aboriginal Protection Board and station managers, in the process formulating a variety of demands for differently conceived rights – to reunion with family members, land, employment and freedom. This article suggests that this correspondence constituted an important tradition of political activism and asks whether gendered definitions of politics have led historians of Aboriginal political struggle to ignore most of the correspondence Aboriginal people sent to the Board and other authorities. By acknowledging the letter writers’ strategies of accommodation, as well as the resistance that has been more widely acknowledged, this article suggests the necessity for some revision of the accepted genealogy of Aboriginal political struggle, and a reconceptualisation of the categories upon which it is based. This article has been peer-reviewed.

In April 1916, 'The Age' ran a short story headed 'Aborigines in camp: Others willing to fight', announcing the presence of two 'full-blooded [sic] natives' among the soldiers at the Ballarat training camp.1 The men's presence blatantly contradicted popular interpretations of the 'Defence Act 1909' (Cth). Only men of 'substantial European origin' were eligible to enlist in the First Australian Imperial Force (AIF), although, in May 1917, the regulations were modified allowing 'half-caste' Aboriginal men entry. The Aboriginal men volunteering to fight in April 1916 were James Arden and Richard King, Gunditjmara men from the Lake Condah Aboriginal Reserve in the Victorian Western District. In the Condah area there was already an acceptance of Aboriginal men's participation in sport and labour; during the First World War, this extended to military service. The men's 'splendid physique' may have justified their acceptance into the military. James Arden was a 'well known rough rider' and Richard King had 'claimed distinction as a footballer and all-round athlete'. The journalist portrayed the spectacle of the Aboriginal men at the Ballarat training camp to promote white men's enlistment. Articles announcing Indigenous enlistments were published across south-eastern Australia during the 1916 and 1917 recruitment drives.

This article examines the ‘case’ of Elsie Barrett, one of a number of girls removed from Victorian Aboriginal missions in the 1910s. Elsie, an ‘Aboriginal’, was removed from Lake Tyers mission, in Gippsland, following her love affair with a ‘half-caste’ man who was banned from the mission. This relationship led to the production of one of the lengthiest case files in the Board for the Protection of Aborigines archive. In this article, I explore the question of what made Elsie's case problematic and investigate her perceived transgression of intersecting moral and legal codes. I suggest that her case is revealing of the way in which preoccupations with Aboriginal women's sexuality overrode the statutory racial distinctions set out in the Aborigines Protection Act of 1886. Central to this article is recognition of the crucial role of gender and sexuality in informing the drafting and implementation of the Victorian Aborigines protection legislation.

AIMS/HYPOTHESIS: We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a single-centre, explanatory randomised controlled trial. METHODS: Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a non-intervention control group. Randomisation and group allocation were conducted by the study co-ordinator, using a software programme. Those with prevalent diabetes, unstable ischaemic heart disease or poor mobility were excluded. All data were collected at our clinical research facility in Cambridge. Components of the metabolic syndrome were used to derive a standardised composite metabolic risk score (zMS) as the primary outcome. Trial status: closed to follow-up. RESULTS: We randomised 100 participants (50 to the intervention, 50 to the control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of participants attended for follow-up measures. There were no serious adverse events. Using an intention-to-treat analysis, we saw a non-significant reduction in zMS in the exercise group compared with controls (0.07 [95% CI -0.03, 0.17], p = 0.19). However, the exercise group had significantly decreased weight, waist circumference and intrahepatic lipid, with increased aerobic fitness and a 68% reduction in prevalence of abnormal glucose metabolism (OR 0.32 [95% CI 0.11-0.92], p = 0.035) compared with controls. Results were similar in per-protocol analyses. CONCLUSIONS/INTERPRETATION: Enrolment in a supervised aerobic exercise intervention led to weight loss, increased fitness and improvements in some but not all metabolic outcomes. In appropriately screened older individuals, such interventions appear to be safe. TRIAL REGISTRATION: Controlled-trials.com ISRCTN60986572 FUNDING: Medical Research Council.

s / Resuscitation 96S (2015) 43–157 119 makes it difficult to obtain informed consent (IC) for clinical studies/trials. Some countries have codified the conditions inwhich the necessity of trial consent is waived in emergency research. Inmany countries, however, IC requirement remains a formidable barrier to conducting such studies. It is important to examine which conditions are effective and advisable in promoting clinical studies/trials in this field. Methods: From the WHO ICTRP (International Clinical Trials Registry Platform) database, trial information, registered in the between 2005 and 2014, was extracted and aggregated for several European countries, the United States and Japan. Overall numbers of registered trials, and those in emergency situations (entries which have “emergency” in title, condition or intervention) were counted. They were tabulated by the study design and countries. Results: Overall, 79,998 clinical trials were registered during the study period. Among this, the number of global clinical trials was 9296(11.6%). The total number of randomised controlled trial (RCT)was 30,717 (38%). Thenumbers of trialswithRCTdesignwere 12,022 (15%) in Europe, 10502 (13%) in the U.S., and 13,317 (17%) in Japan. Among all of clinical trials, 286 (0.36%) were the number of emergency clinical trials; 68 (24%) in Europe, 91 (32%) in the U.S., and 24 (8%) in Japan. The proportions of emergency trials with RCT among all RCT clinical trials in each country were 0.32% in Europe, 0.53% in the U.S., and 0.05% in Japan. Conclusion: There are not many clinical trials conducted in emergency situations. The case is more remarkable with RCTs. This might reflect the difficulty in implementing research due to the conditions and considerations specific to this field. However, the number of RCTwas relatively larger in the U.S., where the guidance on exception from informed consent requirements for emergency research was issued by its regulatory authority. More international exchange of information and discussion is advisable.1,2

Background Survival after out-of-hospital cardiac arrest is closely linked to the quality of CPR, but in real life, resuscitation during prehospital care and ambulance transport is often suboptimal. Mechanical chest compression devices deliver consistent chest compressions, are not prone to fatigue and could potentially overcome some of the limitations of manual chest compression. However, there is no high-quality evidence that they improve clinical outcomes, or that they are cost effective. The Prehospital Randomised Assessment of a Mechanical Compression Device In Cardiac Arrest (PARAMEDIC) trial is a pragmatic cluster randomised study of the LUCAS-2 device in adult patients with non-traumatic out-of-hospital cardiac arrest. Methods/design The primary objective of this trial is to evaluate the effect of chest compression using LUCAS-2 on mortality at 30 days post out-of-hospital cardiac arrest, compared with manual chest compression. Secondary objectives of the study are to evaluate the effects of LUCAS-2 on survival to 12 months, cognitive and quality of life outcomes and cost-effectiveness. Methods: Ambulance service vehicles will be randomised to either manual compression (control) or LUCAS arms. Adult patients in out-of-hospital cardiac arrest, attended by a trial vehicle will be eligible for inclusion. Patients with traumatic cardiac arrest or who are pregnant will be excluded. The trial will recruit approximately 4000 patients from England, Wales and Scotland. A waiver of initial consent has been approved by the Research Ethics Committees. Consent will be sought from survivors for participation in the follow-up phase. Conclusion The trial will assess the clinical and cost effectiveness of the LUCAS-2 mechanical chest compression device. Trial Registration: The trial is registered on the International Standard Randomised Controlled Trial Number Registry (ISRCTN08233942).

BACKGROUND: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4(+) counts compared to no therapy. METHODOLOGY: Participants not on continuous ART with > or = 300 CD4(+) cells/mm(3) were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4(+) counts, HIV RNA, and HIV progression events were collected monthly. PRINCIPAL FINDINGS: A total of 267 participants were randomized. At week 32, the mean CD4(+) count was 134 cells greater in the IL-2 alone group (p

Background: While there are compelling observational data confirming that individuals who exercise are healthier, the efficacy of aerobic exercise interventions to reduce metabolic risk and improve insulin sensitivity in older people has not been fully elucidated. Furthermore, while low birth weight has been shown to predict adverse health outcomes later in life, its influence on the response to aerobic exercise is unknown. Our primary objective is to assess the efficacy of a fully supervised twelve week aerobic exercise intervention in reducing clustered metabolic risk in healthy older adults. A secondary objective is to determine the influence of low birth weight on the response to exercise in this group. Methods/Design: We aim to recruit 100 participants born between 1931–1939, from the Hertfordshire Cohort Study and randomly assign them to no intervention or to 36 fully supervised one hour sessions on a cycle ergometer, over twelve weeks. Each participant will undergo detailed anthropometric and metabolic assessment pre- and post-intervention, including muscle biopsy, magnetic resonance imaging and spectroscopy, objective measurement of physical activity and sub-maximal fitness testing. Discussion: Given the extensive phenotypic characterization, this study will provide valuable insights into the mechanisms underlying the beneficial effects of aerobic exercise as well as the efficacy, feasibility and safety of such interventions in this age group. Trial Registration: Current Controlled Trials: ISRCTN60986572

Few trials have been conducted by UK ambulance services, and well-known examples of trials experiencing difficulties has led to the perception that prehospital care is a difficult environment for trials. PARAMEDIC is an HTA-funded trial comparing mechanical chest compression (using the LUCAS-2 device) with manual chest compression, during attempted resuscitation after cardiac arrest. It is recruiting 4,344 patients from four ambulance services in the UK; the primary outcome is 30 day survival. The trial uses cluster randomisation, with allocation by vehicles. All eligible cardiac arrests where a trial vehicle was first in attendance are included, which. This ensures minimal chance of differential recruitment between the LUCAS and manual chest compression arms, avoiding one of the main threats to cluster randomised trials. The study has raised a number of interesting methodological challenges, including: 1. How to identify all cardiac arrests attended by trial vehicles from multiple imperfect data sources; 2. Movements of vehicles between ambulance stations; trial vehicles often move away from their base station to a non-participating station, and hence do not recruit to the trial; 3. Device management; devices are easily removed from vehicles, and also need to be located for servicing or product recalls; 4. Compliance; although the crews cannot decide not to recruit a patient, they can decide not to use the LUCAS device; there has been significant non-use of the devices, with important consequences for the analysis of the trial.