Effects of three immobilizing drug combinations on ventilation, gas exchange and metabolism in free-living African lions (Panthera leo)

DATA AVAILABILITY : The data underlying this article are available in the article and in its online supplementary material.Free-living lions (12 per group) were immobilized with tiletamine-zolazepam-medetomidine (TZM), ketamine-medetomidine (KM), or ketamine-butorphanol-medetomidine (KBM). During immobilization, respiratory, blood gas and acid–base variables were monitored for 30 minutes. Respiratory rates were within expected ranges and remained constant throughout the immobilizations. Ventilation increased in lions over the immobilization period from 27.2 ± 9.5 to 35.1 ± 25.4 L/min (TZM), 26.1 ± 14.3 to 28.4 ± 18.4 L/min (KM) and 23.2 ± 10.8 to 26.7 ± 14.2 L/min (KBM). Tidal volume increased over the immobilization period from 1800 ± 710 to 2380 ± 1930 mL/breath (TZM), 1580 ± 470 to 1640 ± 500 mL/breath (KM) and 1600 ± 730 to 1820 ± 880 mL/breath (KBM). Carbon dioxide production was initially lower in KBM (0.4 ± 0.2 L/min) than in TZM (0.5 ± 0.2 L/min) lions but increased over time in all groups. Oxygen consumption was 0.6 ± 0.2 L/min (TZM), 0.5 ± 0.2 L/min (KM) and 0.5 ± 0.2 L/min (KBM) and remained constant throughout the immobilization period. Initially the partial pressure of arterial oxygen was lower in KBM (74.0 ± 7.8 mmHg) than in TZM (78.5 ± 4.7 mmHg) lions, but increased to within expected range in all groups over time. The partial pressure of arterial carbon dioxide was higher throughout the immobilizations in KBM (34.5 ± 4.2 mmHg) than in TZM (32.6 ± 2.2 mmHg) and KM (32.6 ± 3.8 mmHg) lions. Alveolar-arterial gradients were initially elevated, but decreased over time for all groups, although in KM lions it remained elevated (26.9 ± 10.4 mmHg) above the expected normal. Overall, all three drug combinations caused minor respiratory and metabolic side-effects in the immobilized lions. However, initially hypoxaemia occurred as the drug combinations, and possibly the stress induced by the immobilization procedure, hinder alveoli oxygen gas exchange.The Copenhagen Zoo and the Kevin Richardson Foundation.https://academic.oup.com/conphysam2024Centre for Veterinary Wildlife StudiesParaclinical SciencesProduction Animal StudiesSDG-03:Good heatlh and well-bein

Comparison of the cardiovascular effects of immobilization with three different drug combinations in free-ranging African lions

DATA AVAILABILITY : The data underlying this article are available in the article and in its online supplementary material.Thirty-six free-ranging lions (12 per group) were immobilized with tiletamine–zolazepam (Zoletil 0.6 mg/kg i.m.) plus medetomidine (0.036 mg/kg i.m.) (TZM), ketamine (3.0 mg/kg i.m.) plus medetomidine (0.036 mg/kg i.m.) (KM) or ketamine (1.2 mg/kg i.m.) plus butorphanol (0.24 mg/kg i.m.) plus medetomidine (0.036 mg/kg i.m.) (KBM). During immobilization cardiovascular variables were monitored at 5-minute intervals for a period of 30 minutes. Lions immobilized with all three drug combinations were severely hypertensive. Systolic arterial pressure was higher at initial sampling in lions immobilized with KM (237.3 ± 24.8 mmHg) than in those immobilized with TZM (221.0 ± 18.1 mmHg) or KBM (226.0 ± 20.6 mmHg) and decreased to 205.8 ± 19.4, 197.7 ± 23.7 and 196.3 ± 17.7 mmHg, respectively. Heart rates were within normal ranges for healthy, awake lions and decreased throughout the immobilization regardless of drug combination used. Lions immobilized with TZM had a higher occurrence (66%) of skipped heart beats than those immobilized with KBM (25%). The three drug combinations all caused negative cardiovascular effects, which were less when KBM was used, but adverse enough to warrant further investigations to determine if these effects can be reversed or prevented when these three combinations are used to immobilize free-living lions.The Copenhagen Zoo.https://academic.oup.com/conphysam2024Centre for Veterinary Wildlife StudiesParaclinical SciencesProduction Animal StudiesSDG-03:Good heatlh and well-bein

Reliability of the enterprise point-of-care (EPOC) blood analyzer's calculated arterial oxygen-hemoglobin saturation in immobilized white rhinoceroses (Ceratotherium simum)

CONCLUSIONS: The EPOC cSaO2 is unreliable and should not be used to monitor blood oxygenation in immobilized white rhinoceroses.Please read abstract in the article.Agriculture Sector Education Training Authority; Centre for Veterinary Wildlife Research; Department of Paraclinical Sciences, University of Pretoria; Department of Veterinary Tropical Diseases, University of Pretoria; Dnata Wild-over-Wildlife; South African Government Health and Welfare Sector Education and Training Authority; Wiederhold Foundation.http://www.wileyonlinelibrary.com/journal/vcpAnatomy and PhysiologyCentre for Veterinary Wildlife StudiesParaclinical SciencesProduction Animal Studie

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Integrated analysis of patient networks and plasmid genomes reveals a regional, multi-species outbreak of carbapenemase-producing Enterobacterales carrying both blaIMP and mcr-9 genes

Background Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of IMP-encoding CPE amongst diverse Enterobacterales species between 2016 and 2019 across a London regional network. Methods We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE positive patients. Genomes of IMP-encoding CPE isolates were overlayed with patient contacts to imply potential transmission events. Results Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, E. coli); 86% (72/84) harboured an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68/72). Phylogenetic analysis of IncHI2 plasmids identified three lineages showing significant association with patient contacts and movements between four hospital sites and across medical specialities, which was missed on initial investigations. Conclusions Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multi-modal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Energy utilisation and postprandial responses during sitting interrupted by regular activity breaks

Interrupting sedentary behaviour with regular activity breaks benefits glycaemic control; however, the influence of the energy utilised during these activity breaks on postprandial metabolic response is relatively unknown. Therefore, the aim of this study was to investigate whether the energy utilisation of regular (every 30 min) short (1 min 40 s or 2 min) activity breaks was associated with the lowering of postprandial glycaemia, insulinemia and lipidemia. Using separate data from two previously performed studies (ALPhA Study n = 65, age 25.7 (5.2) y, 40% male, BMI 23.6 (4.1) kg · m−2. ABPA study n = 35, age 25.1 (3.7) y, 31% male, BMI 23.4 (3.2) kg · m−2) we investigated the association between energy utilisation (measured by indirect calorimetry) and postprandial glucose, insulin and triglycerides during prolonged sitting, and regular activity breaks.Results Mixed effects regression models indicated that energy utilisation was not consistently associated with postprandial glucose, insulin or triglyceride responses (p > 0.05 for all). Additionally, there was some indication that energy utilisation was obscuring (mildly suppressing) the effects of regular activity breaks on glucose, insulin and triglyceride iAUC.Conclusions If energy utilisation does not mediate the association between regular activity breaks and postprandial glycaemic response, it is possible that it is the frequency of the activity breaks that is beneficial

Global, regional, and national burden of traumatic brain injury and spinal cord injury, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016

Background Traumatic brain injury (TBI) and spinal cord injury (SCI) are increasingly recognised as global health priorities in view of the preventability of most injuries and the complex and expensive medical care they necessitate. We aimed to measure the incidence, prevalence, and years of life lived with disability (YLDs) for TBI and SCI from all causes of injury in every country, to describe how these measures have changed between 1990 and 2016, and to estimate the proportion of TBI and SCI cases caused by different types of injury. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016 to measure the global, regional, and national burden of TBI and SCI by age and sex. We measured the incidence and prevalence of all causes of injury requiring medical care in inpatient and outpatient records, literature studies, and survey data. By use of clinical record data, we estimated the proportion of each cause of injury that required medical care that would result in TBI or SCI being considered as the nature of injury. We used literature studies to establish standardised mortality ratios and applied differential equations to convert incidence to prevalence of long-term disability. Finally, we applied GBD disability weights to calculate YLDs. We used a Bayesian meta-regression tool for epidemiological modelling, used cause-specific mortality rates for non-fatal estimation, and adjusted our results for disability experienced with comorbid conditions. We also analysed results on the basis of the Socio-demographic Index, a compound measure of income per capita, education, and fertility. Findings In 2016, there were 27.08 million (95% uncertainty interval [UI] 24.30-30.30 million) new cases of TBI and 0.93 million (0.78-1.16 million) new cases of SCI, with age-standardised incidence rates of 369 (331-412) per 100 000 population for TBI and 13 (11-16) per 100 000 for SCI. In 2016, the number of prevalent cases of TBI was 55.50 million (53.40-57.62 million) and of SCI was 27.04 million (24 .98-30 .15 million). From 1990 to 2016, the age-standardised prevalence of TBI increased by 8.4% (95% UI 7.7 to 9.2), whereas that of SCI did not change significantly (-0.2% [-2.1 to 2.7]). Age-standardised incidence rates increased by 3.6% (1.8 to 5.5) for TBI, but did not change significantly for SCI (-3.6% [-7.4 to 4.0]). TBI caused 8.1 million (95% UI 6. 0-10. 4 million) YLDs and SCI caused 9.5 million (6.7-12.4 million) YLDs in 2016, corresponding to age-standardised rates of 111 (82-141) per 100 000 for TBI and 130 (90-170) per 100 000 for SCI. Falls and road injuries were the leading causes of new cases of TBI and SCI in most regions. Interpretation TBI and SCI constitute a considerable portion of the global injury burden and are caused primarily by falls and road injuries. The increase in incidence of TBI over time might continue in view of increases in population density, population ageing, and increasing use of motor vehicles, motorcycles, and bicycles. The number of individuals living with SCI is expected to increase in view of population growth, which is concerning because of the specialised care that people with SCI can require. Our study was limited by data sparsity in some regions, and it will be important to invest greater resources in collection of data for TBI and SCI to improve the accuracy of future assessments. Copyright (C) 2018 The Author(s). Published by Elsevier Ltd.Peer reviewe

Palaeontology from Australasia and beyond: Abstracts from Palaeo Down Under 3 Perth, Western Australia, July 2023

Palaeo Down Under 3 (PDU3), the now quadrennial conference of the Australasian Palaeontologists (AAP) association, was held in Perth, Western Australia, from the 10th-14th of July 2023. PDU3 showcased innovative research, outreach and education initiatives being conducted across Australasia and beyond by both local and international scientists. A total of 78 talks, 17 posters and 6 plenaries were presented across the five days, and covered a wide range of topics, geological timeframes, and fossil groups. AAP is proud to publish this compilation of PDU3 abstracts to illustrate the current and ongoing strength of Australasian palaeontology. Sarah K. Martin [ [email protected] ], Geological Survey of Western Australia, Department of Energy, Mines, Industry Regulation and Safety, 100 Plain St, East Perth, Western Australia 6004, Australia; Michael Archer [ [email protected] ], School of Biological, Earth & Environmental Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia; Heidi J. Allen [ [email protected] ], Geological Survey of Western Australia, Department of Energy, Mines, Industry Regulation and Safety, 100 Plain St, East Perth, Western Australia 6004, Australia; Daniel D. Badea [ [email protected] ], Faculty of Geography and Geology, "Alexandru Ioan Cuza" University, Bulevard "Carol I", Nr.11, 707006, Iași, Romania; Eleanor Beidatsch [ [email protected] ], Palaeoscience Research Centre, University of New England, Armidale, New South Wales 2351, Australia; Marissa J. Betts [ [email protected] ], Palaeoscience Research Centre/LLUNE, University of New England, Armidale, New South Wales 2351, Australia; Maria Blake [ [email protected] ], School of Earth, Atmosphere and Environment, Monash University, 9 Rainforest Walk, Clayton, Victoria 3800, Australia; Phillip C. Boan [ [email protected] ], University of California, Riverside, Geology 1242, 900 University Ave, Riverside, CA 92521, U.S.A.; Tory Botha [ [email protected] ], School of Biological Sciences, Molecular Life Sciences Building, North Terrace Campus, The University of Adelaide, Adelaide, South Australia 5005, Australia; Glenn A. Brock [ [email protected] ], School of Natural Sciences, Macquarie University, New South Wales 2109, Australia; Luke Brosnan [ [email protected] ], WA Organic and Isotope Geochemistry Centre, The Institute for Geoscience Research, School of Earth and Planetary Sciences, Building 500, Curtin University, Kent St, Bentley, Western Australia 6102, Australia; Jack Castle-Jones [ [email protected] ], School of Natural Sciences, Macquarie University, New South Wales 2109, Australia; Jonathan Cramb [ [email protected] ], Queensland Museum, PO Box 3300, South Brisbane BC, Queensland 4101, Australia; Vanesa L. De Pietri [ [email protected] ], School of Earth and Environment, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand; Sherri Donaldson [ [email protected] ], School of Geosciences, University of Edinburgh, Grant Institute, The King's Buildings, James Hutton Road, Edinburgh, EH9 3FE, Scotland, U.K.; Elizabeth M. Dowding [ [email protected] ], Friedrich-Alexander-Universität Erlangen-Nürnberg, Loewenichstraße 28 91054 Erlangen, Germany; Ruairidh Duncan [ [email protected] ], Evans EvoMorph Lab, Room 226, 18 Innovation Walk, School of Biological Sciences, Monash University, Clayton, Victoria 3800, Australia; Amy L. Elson [ [email protected] ], WA Organic and Isotope Geochemistry Centre, The Institute for Geoscience Research, School of Earth and Planetary Sciences, Building 500, Curtin University, Kent St, Bentley, Western Australia 6102, Australia; Roy M. Farman [ [email protected] ], School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales 2052, Australia; Mahala A. Fergusen [ [email protected] ], School of Biological Sciences, Benham Building, North Terrace Campus, The University of Adelaide, Adelaide, South Australia 5005, Australia; Alyssa Fjeld [ [email protected] ], School of Biological Sciences, 18 Innovation Walk, Monash University, Clayton, Victoria 3800, and School of Natural Sciences, Macquarie University, New South Wales 2109, Australia; David Flannery [ [email protected] ], School of Earth and Atmospheric Sciences, Queensland University of Technology, 2 George St, Brisbane, Queensland 4000, Australia; Timothy G. Frauenfelder [ [email protected] ], University of New England, Armidale, New South Wales 2351, Australia; John D. Gorter [ [email protected] ], PO Box 711, Claremont, Western Australia 6910, Australia; Michelle Gray [ [email protected] ], School of Life and Environmental Sciences, Deakin University, Geelong, Victoria 3216, Australia; Nigel Gray [ [email protected] ], GPO Box 2902, Brisbane, Queensland 4001, Australia; Peter Haines [ [email protected] ], Geological Survey of Western Australia, Department of Energy, Mines, Industry Regulation and Safety, 100 Plain St, East Perth, Western Australia 6004, Australia; Lachlan J. Hart [ [email protected] ], Australian Museum Research Institute, 1 William Street, Sydney, New South Wales 2010, Australia; Brooke E. Holland [ [email protected] ], School of Biological Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia; James D. Holmes [ [email protected] ], Department of Earth Sciences, Palaeobiology, Uppsala University, Villavägen 16, Uppsala 752 36, Sweden; Lars Holmer [ [email protected] ], Department of Earth Sciences, Palaeobiology, Uppsala University, Villavägen 16, Uppsala 752 36, Sweden; Ashleigh V.S. Hood [ [email protected] ], School of Geography, Earth and Atmospheric Sciences, University of Melbourne, Parkville, Victoria 3010, Australia; Alexey P. Ippolitov [ [email protected]] , School of Geography, Environment and Earth Sciences, Victoria University of Wellington | Te Herenga Waka, 21 Kelburn Parade, Wellington 6012, New Zealand; Christine M. Janis [ [email protected] ], Bristol Palaeobiology Group, School of Earth Sciences, University of Bristol, Wills Memorial Building, Bristol, BS8 1RJ, U.K.; Benjamin P. Kear [ [email protected] ], The Museum of Evolution, Uppsala University, Norbyvägen 16, SE-752 36 Uppsala, Sweden; Sophie Kelly [ [email protected] ], School of Earth and Environment, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand; Justin L. Kitchener [ [email protected] ], School of Environmental and Rural Science, University of New England, Armidale, New South Wales 2351, Australia; John R. Laurie [ [email protected] ], Geoscience Australia, Symonston, Australian Capital Territory 2601, and School of Natural Sciences, Macquarie University, North Ryde, New South Wales 2109, Australia; Lucy G. Leahey [ [email protected] ], The University of Queensland, Brisbane, Queensland 4072, Australia; John A. Long [ [email protected] ], College of Science and Engineering, Flinders University, PO Box 2100, Adelaide, South Australia 5001, Australia; Daniel Mantle [ [email protected] ], MGPalaeo, Unit 1, 5 Arvida Street, Malaga, Western Australia 6090, Australia; David McB. Martin [ [email protected] ], Geological Survey of Western Australia, Department of Energy, Mines, Industry Regulation and Safety, 100 Plain St, East Perth, Western Australia 6004, Australia; Chris Mays [ [email protected] ], School of Biological, Earth and Environmental Sciences, Environmental Research Institute, University College Cork, Distillery Fields, Cork T23 N73K, Ireland; Matthew R. McCurry [ [email protected] ], Australian Museum, 1 William St, Sydney, New South Wales 2010, Australia; Peter McGoldrick [ [email protected] ], CODES, University of Tasmania, Locked Bag 66, Hobart, Tasmania 7001, Australia; Corinne L. Mensforth [ [email protected] ], Flinders University, GPO Box 2100, Adelaide, South Australia 5001, Australia; Rhys D. Meyerkort [ [email protected] ], University of Western Australia, 35 Stirling Hwy, Crawley, Western Australia 6009, Australia; Christina Nielsen-Smith [ [email protected] ], School of Biological Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia; Ryan Nel [ [email protected] ], Geology Department, Rhodes University, Grahamstown, South Africa; Jake Newman-Martin [ [email protected] ], Curtin University, Kent St, Bentley, Western Australia 6102, Australia; Yeongju Oh [ [email protected] ], Division of Earth Sciences, Korea Polar Research Institute, 26 Songdomirae-ro, Yeonsu-gu, 21990 Incheon, Republic of Korea, and Polar Science, University of Science and Technology, Daejeon, 34113, Republic of Korea; John R. Paterson [ [email protected] ], Palaeoscience Research Centre, School of Environmental and Rural Science, University of New England, Armidale, New South Wales 2351, Australia; Jacob Pears [ [email protected] ], School of Molecular and Life Sciences, Curtin University, Kent St, Bentley, Western Australia 6102, Australia; Stephen F. Poropat [ [email protected] ], Western Australian Organic and Isotope Geochemistry Centre, School of Earth and Planetary Science, Curtin University, Kent St, Bentley, Western Australia 6102, and Australian Age of Dinosaurs Museum of Natural History, Winton, Queensland 4735, Australia; Catherine M. Reid [ [email protected] ], School of Earth and Environment, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand; R. Pamela Reid [ [email protected] ], Department of Marine Geosciences, Rosenstiel School of Marine, Atmospheric, and Earth Science, University of Miami, Miami, FL 33149, U.S.A., and Bahamas Marine EcoCentre, Miami, FL 3315

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases:subgroup analyses of the RESTART randomised, open-label trial

Background: Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy. Methods: RESTART was a prospective, randomised, open-label, blinded-endpoint, parallel-group trial at 122 hospitals in the UK that assessed whether starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. For this prespecified subgroup analysis, consultant neuroradiologists masked to treatment allocation reviewed brain CT or MRI scans performed before randomisation to confirm participant eligibility and rate features of the intracerebral haemorrhage and surrounding brain. We followed participants for primary (recurrent symptomatic intracerebral haemorrhage) and secondary (ischaemic stroke) outcomes for up to 5 years (reported elsewhere). For this report, we analysed eligible participants with intracerebral haemorrhage according to their treatment allocation in primary subgroup analyses of cerebral microbleeds on MRI and in exploratory subgroup analyses of other features on CT or MRI. The trial is registered with the ISRCTN registry, number ISRCTN71907627. Findings: Between May 22, 2013, and May 31, 2018, 537 participants were enrolled, of whom 525 (98%) had intracerebral haemorrhage: 507 (97%) were diagnosed on CT (252 assigned to start antiplatelet therapy and 255 assigned to avoid antiplatelet therapy, of whom one withdrew and was not analysed) and 254 (48%) underwent the required brain MRI protocol (122 in the start antiplatelet therapy group and 132 in the avoid antiplatelet therapy group). There were no clinically or statistically significant hazards of antiplatelet therapy on recurrent intracerebral haemorrhage in primary subgroup analyses of cerebral microbleed presence (2 or more) versus absence (0 or 1) (adjusted hazard ratio [HR] 0·30 [95% CI 0·08–1·13] vs 0·77 [0·13–4·61]; pinteraction=0·41), cerebral microbleed number 0–1 versus 2–4 versus 5 or more (HR 0·77 [0·13–4·62] vs 0·32 [0·03–3·66] vs 0·33 [0·07–1·60]; pinteraction=0·75), or cerebral microbleed strictly lobar versus other location (HR 0·52 [0·004–6·79] vs 0·37 [0·09–1·28]; pinteraction=0·85). There was no evidence of heterogeneity in the effects of antiplatelet therapy in any exploratory subgroup analyses (all pinteraction>0·05). Interpretation: Our findings exclude all but a very modest harmful effect of antiplatelet therapy on recurrent intracerebral haemorrhage in the presence of cerebral microbleeds. Further randomised trials are needed to replicate these findings and investigate them with greater precision. Funding: British Heart Foundation