The thinking behind the action (learning): Reflections on the design and delivery of an executive management program

Purpose - The purpose of this paper is to report on an action learning (AL) approach to curriculum design and delivery of a two-year part-time executive masters program, facilitated in part through a longitudinal work-based action research project. Program participants were a mix of mid- to senior managers operating in both the public and private sector and business owners, and all were in full-time employment. Design/methodology/approach - This paper presents findings relating to participant and tutor perspectives of the program design, structure, and content. It also chronicles an AL tutor initiative run in conjunction with the inaugural program delivery, established to provide a collegial approach to learner facilitation, and to enable a research informed model of practice. Findings - Findings suggest that the program allowed for greater action-reflection among and across all contributors (students, tutors, and program managers), and facilitated cross-pollination of AL perspectives, thus strengthening the interaction between practitioner and academic, and among academics themselves. Furthermore, the early involvement of tutors informed the work-based research project and larger AL program, and facilitated a matching of research interests between practitioner and tutor. Originality/value - These findings suggest that an action-based model of knowledge transfer and development offers significant learning benefits to those partaking in an executive development program, resulting in the following insights: executive needs better served using a learner-centric approach; problem-oriented work-based assessment affords theory–practice balance; there is evidence of action-reflection “contagion” among all contributors; and the presented AL cycle has potential value in the conceptualization of reflective action

Biological Misinterpretation of Transcriptional Signatures in Tumor Samples Can Unknowingly Undermine Mechanistic Understanding and Faithful Alignment with Preclinical Data

PURPOSE Precise mechanism-based gene expression signatures (GES) have been developed in appropriate in vitro and in vivo model systems, to identify important cancer-related signaling processes. However, some GESs originally developed to represent specific disease processes, primarily with an epithelial cell focus, are being applied to heterogeneous tumor samples where the expression of the genes in the signature may no longer be epithelial-specific. Therefore, unknowingly, even small changes in tumor stroma percentage can directly influence GESs, undermining the intended mechanistic signaling. EXPERIMENTAL DESIGN Using colorectal cancer as an exemplar, we deployed numerous orthogonal profiling methodologies, including laser capture microdissection, flow cytometry, bulk and multiregional biopsy clinical samples, single-cell RNA sequencing and finally spatial transcriptomics, to perform a comprehensive assessment of the potential for the most widely used GESs to be influenced, or confounded, by stromal content in tumor tissue. To complement this work, we generated a freely-available resource, ConfoundR; https://confoundr.qub.ac.uk/, that enables users to test the extent of stromal influence on an unlimited number of the genes/signatures simultaneously across colorectal, breast, pancreatic, ovarian and prostate cancer datasets. RESULTS Findings presented here demonstrate the clear potential for misinterpretation of the meaning of GESs, due to widespread stromal influences, which in-turn can undermine faithful alignment between clinical samples and preclinical data/models, particularly cell lines and organoids, or tumor models not fully recapitulating the stromal and immune microenvironment. CONCLUSIONS Efforts to faithfully align preclinical models of disease using phenotypically-designed GESs must ensure that the signatures themselves remain representative of the same biology when applied to clinical samples

Crop Updates 2007 - Cereals

This session covers twenty six papers from different authors: CEREAL BREEDING 1. Strategies for aligning producer and market imperatives in cereal breeding in Western Australia, R. Loughman, R. Lance, I. Barclay, G. Crosbie, S. Harasymow, W. Lambe, C. Li, R. McLean, C. Moore, K. Stefanova, A. Tarr and R. Wilson, Department of Agriculture and Food 2. LongReach plant breeders wheat variety trials – 2006, Matu Peipi and Matt Whiting, LongReach Plant Breeders WHEAT AGRONOMY 3. Response of wheat varieties to sowing time in the northern agricultural region in 2006, Christine Zaicou, Department of Agriculture and Food 4. Response of wheat varieties to sowing time in the central agricultural region in 2006, Shahajahan Miyan, Department of Agriculture and Food 5. Response of wheat varieties to sowing time in the Great Southern and Lakes region, Brenda Shackleyand Ian Hartley, Department of Agriculture and Food 6. Response of wheat varieties to time of sowing time in Esperance region in 2006, Christine Zaicou, Ben Curtis and Ian Hartley, Department of Agriculture and Food 7. Performance of wheat varieties in National Variety Testing (NVT) WA: Year 2, Peter Burgess, Agritech Crop Research 8. Flowering dates of wheat varieties in Western Australia in 2006, Darshan Sharma, Brenda Shackley and Christine Zaicou, Department of Agriculture and Food 9. Prospects for perennial wheat: A feasibility study, Len J. Wade, Lindsay W. Bell, Felicity Byrne (nee Flugge) and Mike A. Ewing, School of Plant Biology and CRC for Plant-based Management of Dryland Salinity, The University of Western Australia BARLEY AGRONOMY 10. Barley agronomy highlights: Time of sowing x variety, Blakely Paynter and Andrea Hills, Department of Agriculture and Food 11. Barley agronomy highlights: Weeds and row spacing, Blakely Paynter and Andrea Hills, Department of Agriculture and Food 12. Barley agronomy highlights: Weeds and barley variety, Blakely Paynter and Andrea Hills, Department of Agriculture and Food OAT AGRONOMY 13. Agronomic performance of dwarf potential milling oat varieties in varied environments of WA, Raj Malik, Blakely Paynter and Kellie Winfield, Department of Agriculture and Food 14. Sourcing oat production information in 2007, Kellie Winfield, Department of Agriculture and Food HERBICIDE TOLERANCE 15. Response of new wheat varieties to herbicides, Harmohinder Dhammu, Department of Agriculture and Food 16. Herbicide tolerance of new barley varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Food 17. Herbicide tolerance of new oat varieties, Harmohinder Dhammu, Vince Lambert and Chris Roberts, Department of Agriculture and Food NUTRITION 18. Nitrogen Decision Tools – choose your weapon, Jeremy Lemon, Department of Agriculture and Food DISEASES 19. Barley agronomy highlights: Canopy management, Andrea Hills and Blakely Paynter, Department of Agriculture and Food 20. Barley agronomy highlights: Leaf diseases and spots, Andrea Hills and Blakely Paynter, Department of Agriculture and Food 21. Fungicide applications for stripe rust management in adult plant resistant (APR) wheat varieties, Geoff Thomas, Rob Loughman, Ian Hartley and Andrew Taylor; Department of Agriculture and Food 22. Effect of seed treatment with Jockey on time of onset and disease severity of stripe rust in wheat, Manisha Shankar, John Majewski and Rob Loughman, Department of Agriculture and Food 23. Rotations for management of Cereal Cyst Nematode, Vivien Vanstone, Department of Agriculture and Food 24. Occurrence of Wheat Streak Mosaic Virus in Western Australian grainbelt during the 2006 growing season, Brenda Coutts, Monica Kehoe and Roger Jones, Department of Agriculture and Food 25. Development of a seed test for Wheat Streak Mosaic Virus in bulk samples of wheat, Geoffrey Dwyer, Belinda Welsh, Cuiping Wang and Roger Jones, Department of Agriculture and Food MARKETS 26. Developing the Australian barley value chain, Linda Price, Barley Australi

Crop Updates 2009 - Cereals

This session covers twenty seven papers from different authors: PLENARY 1. Building soil carbon for productivity and implications for carbon accounting, Jeff Baldock, CSIRO Land and Water, Adelaide, SA 2. Fact or Fiction: Who is telling the truth and how to tell the difference, Doug Edmeades, agKnowledge Ltd, Hamilton 3. Four decades of crop sequence trials in Western Australia, Mark Seymour,Department of Agriculture and Food BREAK CROPS 4. 2008 Break Crops survey Report, Paul Carmody,Development Officer, Department of Agriculture and Food 5. Attitudes of Western Australian wheatbelt growers to ‘Break Crops’, Paul Carmody and Ian Pritchard, Development Officers, Department of Agriculture and Food 6. The value of organic nitrogen from lupins, Alan Meldrum, Pulse Australia 7.The area of break crops on farm: What farmers are doing compared to estimates based on maximising profit, Michael Robertson and Roger Lawes,CSIRO Floreat, Rob Sands,FARMANCO Farm Consultants, Peter White,Department of Agriculture and Food, Western Australia, Felicity Byrne and Andrew Bathgate,Farming Systems Analysis CROP SPECIFIC Breeding 8. Identification of WALAB2014 as a potential albus lupin variety for northern agricultural region of Western Australia, Kedar Adhikari, Department of Agriculture and Food 9. Enhancement of black spot resistance in field pea, Kedar Adhikari, Tanveer Khan, Stuart Morgan and Alan Harris, Department of Agriculture and Food 10. Desi chickpea breeding: Evaluation of advanced line, Khan, TN1, Harris, A1, Gaur, P2, Siddique, KHM3, Clarke, H4, Turner, NC4, MacLeod, W1, Morgan, S1 1Department of Agriculture and Food, Western Australia, 2International Crop Research Institute for the Semi Arid Tropics (ICRISAT), 3The University of Western Australia, 4Centre for Legumes in Mediterranean Agriculture 11. Pulse Breeding Australia-Australian Field Pea Improvement Program (AFPIP), Ian Pritchard1, Chris Veitch1, Stuart Morgan1, Alan Harris1 and Tony Leonforte 2 1 Department of Agriculture and Food, Western Australia, 2 Department off Primary Industries, Victoria Disease 12. Interaction between wheat varieties and fungicides to control stripe rust for grain and quality, Kith Jayasena, Geoff Thomas, Rob Loughman, Kazue Tanaka and Bill MacLeod, Department of Agriculture and Food 13. Findings of canola disease survey 2008 and its implications for better disease management in 2009, Ravjit Khangura, WJ MacLeod, P White, P Carmody and M Amjad, Department of Agriculture and Food 14. Combating wheat leaf diseases using genome sequencing and functional genomics, Richard Oliver, Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University 15. Distribution and survival of wheat curl mite (Aceria tosichella), vector of Wheat Streak Mosaic Virus, in the WA grainbelt during 2008, Dusty Severtson, Peter Mangano, John Botha and Brenda Coutts, Department of Agriculture and Food 16. Partial resistance to Stagonspora (Septoria) Partial resistance to Stagonospora (Septoria) nodorum blotch and response to fungicide in a severe epidemic scenario, Manisha Shankar1, Richard Oliver2, Kasia Rybak2and Rob Loughman1 1Department of Agriculture and Food, Western Australia, 2Australian Centre for Necrotrophic Fungal Pathogens, Murdoch University, Western Australia 17. Black pod syndrome in lupins can be reduced by regular insecticide sprays, Peter White and Michael Baker,Department of Agriculture and Food Variety performance 18. Incorporating new herbicide tolerant juncea canola into low rainfall cropping systems in Western Australia, Mohammad Amjad, Department of Agriculture and Food 19. Varietal differences in germ end staining of barley, Andrea Hills,Department of Agriculture and Food 20. Wheat variety performance in the Central Agricultural Region in 2008, Shahajahan Miyan, Department of Agriculture and Food 21. Barley variety identification using DNA fingerprinting, Peter Portmann, Agriconnect, Perth WA Dr Nicole Rice, Southern Cross University, Lismore NSW Prof Robert Henry, Southern Cross University, Lismore NSW 22. Forecast disease resistance profile for the Western Australian barley crop over the next three years, Jeff J. Russell, Department of Agriculture and Food 23. Malting barley varieties differ in their flowering date and their response to changes in sowing date, BH Paynter and Jeff J. Russell,Department of Agriculture and Food 24. Market development for new barley varieties, Linda Price,Barley Australia 25. Response of wheat varieties to sowing time at Mt Barker, Katanning and Newdegate in 2008, Brenda Shackley and Vicki Scanlan,Department of Agriculture and Food 26. Flowering dates of wheat varieties in 2008 at three locations in Western Australia, Darshan Sharma, Brenda Shackley and Christine Zaicou-Kunesch, Department of Agriculture and Food 27. Agronomic responses of new wheat varieties in the norther agricultural region in 2008, Christine Zaicou-Kunesch, Department of Agriculture and Foo

Crop Updates 2007 - Farming Systems

This session covers forty papers from different authors: 1. Quality Assurance and industry stewardship, David Jeffries, Better Farm IQ Manager, Cooperative Bulk Handling 2. Sothis: Trifolium dasyurum (Eastern Star clover), A. Loi, B.J. Nutt and C.K. Revell, Department of Agriculture and Food 3. Poor performing patches of the paddock – to ameliorate or live with low yield? Yvette Oliver1, Michael Robertson1, Bill Bowden2, Kit Leake3and Ashley Bonser3, CSIRO Sustainable Ecosystems1, Department of Food and Agriculture2, Kellerberrin Farmer3 4. What evidence is there that PA can pay? Michael Robertson, CSIRO Floreat, Ian Maling, SilverFox Solutions and Bindi Isbister, Department of Agriculture and Food 5.The journey is great, but does PA pay? Garren Knell, ConsultAg; Alison Slade, Department of Agriculture and Food, CFIG 6. 2007 Seasonal outlook, David Stephens and Michael Meuleners, Department of Agriculture and Food 7. Towards building farmer capacity to better manage climate risk, David Beard and Nicolyn Short, Department of Agriculture and Food 8. A NAR farmers view of his farming system in 2015, Rob Grima, Department of Agriculture and Food 9. Biofuels opportunities in Australia, Ingrid Richardson, Food and Agribusiness Research, Rabobank 10. The groundwater depth on the hydrological benefits of lucerne and the subsequent recharge values, Ruhi Ferdowsian1and Geoff Bee2; 1Department of Agriculture and Food, 2Landholder, Laurinya, Jerramungup 11. Subsoil constraints to crop production in the high rainfall zone of Western Australia, Daniel Evans1, Bob Gilkes1, Senthold Asseng2and Jim Dixon3; 1University of Western Australia, 2CSIRO Plant Industry, 3Department of Agriculture and Food 12. Prospects for lucerne in the WA wheatbelt, Michael Robertson, CSIRO Floreat, Felicity Byrne and Mike Ewing, CRC for Plant-Based Management of Dryland Salinity, Dennis van Gool, Department of Agriculture and Food 13. Nitrous oxide emissions from a cropped soil in the Western Australian grainbelt, Louise Barton1, Ralf Kiese2, David Gatter3, Klaus Butterbach-Bahl2, Renee Buck1, Christoph Hinz1and Daniel Murphy1,1School of Earth and Geographical Sciences, The University of Western Australia, 2Institute for Meteorology and Climate Research, Atmospheric Environmental Research, Garmisch-Partenkirchen, Germany, 3The Department of Agriculture and Food 14. Managing seasonal risk is an important part of farm management but is highly complex and therefore needs a ‘horses for courses’ approach, Cameron Weeks, Planfarm / Mingenew-Irwin Group, Dr Michael Robertson, Dr Yvette Oliver, CSIRO Sustainable Ecosystems and Dr Meredith Fairbanks, Department of Agriculture and Food 15. Novel use application of clopyralid in lupins, John Peirce, and Brad Rayner Department of Agriculture and Food 16. Long season wheat on the South Coast – Feed and grain in a dry year – a 2006 case study, Sandy White, Department of Agriculture and Food 17. Wheat yield response to potassium and the residual value of PKS fertiliser drilled at different depths, Paul Damon1, Bill Bowden2, Qifu Ma1 and Zed Rengel1; Faculty of Natural and Agricultural Sciences, The University of Western Australia1, Department of Agriculture and Food2 18. Saltbush as a sponge for summer rain, Ed Barrett-Lennard and Meir Altman, Department of Agriculture and Food and CRC for Plant-based Management of Dryland Salinity 19. Building strong working relationships between grower groups and their industry partners, Tracey M. Gianatti, Grower Group Alliance 20. To graze or not to graze – the question of tactical grazing of cereal crops, Lindsay Bell and Michael Robertson, CSIRO Sustainable Ecosystems 21. Can legume pastures and sheep replace lupins? Ben Webb and Caroline Peek, Department of Agriculture and Food 22. EverGraze – livestock and perennial pasture performance during a drought year, Paul Sanford, Department of Agriculture and Food, and CRC for Plant-based Management of Dryland Salinity 23. Crop survival in challenging times, Paul Blackwell1, Glen Riethmuller1, Darshan Sharma1and Mike Collins21Department of Agriculture and Food, 2Okura Plantations, Kirikiri New Zealand 24. Soil health constraints to production potential – a precision guided project, Frank D’Emden, and David Hall, Department of Agriculture and Food 25. A review of pest and disease occurrence in 2006, Mangano, G.P. and Severtson, D.L., Department of Agriculture and Food 26. e-weed – an information resource on seasonal weed management issues, Vanessa Stewart and Julie Roche, Department of Agriculture and Food 27. Review of Pesticide Legislation and Policies in Western Australia, Peter Rutherford, BSc (Agric.), Pesticide Legislation Review, Office of the Chief Medical Adviser, WA Department of Health 28. Future wheat yields in the West Australian wheatbelt, Imma Farré and Ian Foster, Department of Agriculture and Food, Stephen Charles, CSIRO Land and Water 29. Organic matter in WA arable soils: What’s active and what’s not, Frances Hoyle, Department of Agriculture and Food, Australia and Daniel Murphy, UWA 30. Soil quality indicators in Western Australian farming systems, D.V. Murphy1, N. Milton1, M. Osman1, F.C. Hoyle2, L.K Abbott1, W.R. Cookson1and S. Darmawanto1; 1UWA, 2Department of Agriculture and Food 31. Impact of stubble on input efficiencies, Geoff Anderson, formerly employed by Department of Agriculture and Food 32. Mixed farming vs All crop – true profit, not just gross margins, Rob Sands and David McCarthy, FARMANCO Management Consultants, Western Australia 33. Evaluation of Local Farmer Group Network – group leaders’ surveys 2005 and 2006, Paul Carmody, Local Farmer Group Network, Network Coordinator, UWA 34. Seeding rate and nitrogen application and timing effects in wheat, J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 35. Foliar fungicide application and disease control in barley, J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 36. Brown manuring effects on a following wheat crop in the central wheatbelt, , J. Russell, Department of Agriculture and Food, J. Eyres, G. Fosbery and A. Roe, ConsultAg, Northam 37. Management of annual pastures in mixed farming systems – transition from a dry season, Dr Clinton Revell and Dr Phil Nichols; Department of Agriculture and Food 38. The value of new annual pastures in mixed farm businesses of the wheatbelt, Dr Clinton Revell1, Mr Andrew Bathgate2and Dr Phil Nichols1; 1Department of Agriculture and Food, 2Farming Systems Analysis Service, Albany 39. The influence of winter SOI and Indian Ocean SST on WA winter rainfall, Meredith Fairbanks and Ian Foster, Department of Agriculture and Food 40. Market outlook – Grains, Anne Wilkins, Market Analyst, Grains, Department of Agriculture and Foo

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A preliminary whole-farm economic analysis of perennial wheat in an Australian dryland farming system

The development of perennial wheat could have a number of advantages for improving the sustainability of Australian dryland agricultural systems. The profitability that might be expected from perennial wheat of different types was investigated using MIDAS (Model of an Integrated Dryland Agricultural System), a bioeconomic model of a mixed crop/livestock farming system. Although perennial wheat may produce a lower grain yield and quality than annual wheat, it is expected inputs of fertiliser, herbicide and sowing costs will be lower. Perennial wheat used solely for grain production was not selected as part of an optimal farm plan under the standard assumptions. In contrast, dual-purpose perennial wheat that produces grain and additional forage during summer and autumn than annual wheat can increase farm profitability substantially (AU$20/ha over the whole farm) and 20% of farm area was selected on the optimal farm plan under standard assumptions. Forage from perennial wheat replaced stubble over summer and grain supplement at the break of season and increased farm stock numbers. The additional value added by grazing also reduced the relative yield required for perennial wheat to be profitable. This analysis suggests perennial wheat used for the dual purposes of grain and forage production could be developed as a profitable option for mixed crop/livestock producers