COVID-19 and myocarditis: a systematic review and overview of current challenges

Myocardial inflammation in COVID-19 has been documented. Its pathogenesis is not fully elucidated, but the two main theories foresee a direct role of ACE2 receptor and a hyperimmune response, which may also lead to isolated presentation of COVID-19-mediated myocarditis. The frequency and prognostic impact of COVID-19-mediated myocarditis is unknown. This review aims to summarise current evidence on this topic. We performed a systematic review of MEDLINE and Cochrane Library (1/12/19–30/09/20). We also searched clinicaltrials.gov for unpublished studies testing therapies with potential implication for COVID-19-mediated cardiovascular complication. Eligible studies had laboratory confirmed COVID-19 and a clinical and/or histological diagnosis of myocarditis by ESC or WHO/ISFC criteria. Reports of 38 cases were included (26 male patients, 24 aged < 50 years). The first histologically proven case was a virus-negative lymphocytic myocarditis; however, biopsy evidence of myocarditis secondary to SARS-CoV-2 cardiotropism has been recently demonstrated. Histological data was found in 12 cases (8 EMB and 4 autopsies) and CMR was the main imaging modality to confirm a diagnosis of myocarditis (25 patients). There was a substantial variability in biventricular systolic function during the acute episode and in therapeutic regimen used. Five patients died in hospital. Cause-effect relationship between SARS-CoV-2 infection and myocarditis is difficult to demonstrate. However, current evidence demonstrates myocardial inflammation with or without direct cardiomyocyte damage, suggesting different pathophysiology mechanisms responsible of COVID-mediated myocarditis. Established clinical approaches should be pursued until future evidence support different actions. Large multicentre registries are advisable to elucidate further

Effectiveness of direct egfr mutations research at time of diagnostic biopsy for lung cancer: a single institution outcome research

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Timing of sentinel node biopsy independently predicts disease-free and overall survival in clinical stage I-II melanoma patients: A multicentre study of the Italian Melanoma Intergroup (IMI)

Background: Sentinel lymph node biopsy (SNB) still remains a key procedure to appropriately stage melanoma patients and to select those who are candidate to novel treatments with immunotherapy and targeted therapy in the adjuvant setting. The impact of timing of SNB on disease-free survival (DFS) and overall survival (OS) is still unclear. Material and methods: The study was conducted at 6 Italian Melanoma Intergroup (IMI) centres and included 8953 consecutive clinical stage I-II melanoma patients who were diagnosed, treated, and followed up between November 1997 and March 2018. All patients were prospectively included in dedicated IMI database. Multivariable Cox regression analyses were performed to investigate how baseline characteristics and time interval until SNB are related to DFS and OS. Results: Considering the whole population, at multivariable analysis, after adjusting for age, gender, Breslow thickness, site, ulceration, and the SNB status, a delay in the timing of SNB was associated with a better DFS (adjusted hazard ratio [aHR, delayed versus early SNB] 0.98, 95% confidence interval [CI] 0.97\u20130.99, p < 0.001) and OS (aHR 0.98, 95% CI 0.97\u20130.99, p = 0.001). Specifically, in patients with a negative SNB status, a beneficial impact of delayed SNB (i.e. at least 32 days after primary excision) was confirmed for DFS (aHR 0.70, 95%CI 0.63\u20130.79, p < 0.001) and OS (aHR 0.69, 95%CI 0.61\u20130.78, p < 0.001), whereas in those with a positive SNB status, DFS (aHR 0.96, 95%CI 0.84\u20131.09, p = 0.534) and OS (aHR 0.94 95%CI 0.81\u20131.08, p = 0.374) were not significantly different in patients with early or delayed SNB. Conclusions: Our study does not support a strict time interval for SNB. These results may be useful for national guidelines, for counselling patients and reducing the number of high urgency referrals

Non-small cell lung cancer testing on reference specimens: an italian multicenter experience

Introduction: Biomarker testing is mandatory for the clinical management of patients with advanced non-small cell lung cancer (NSCLC). Myriads of technical platforms are now available for biomarker analysis with differences in terms of multiplexing capability, analytical sensitivity, and turnaround time (TAT). We evaluated the technical performance of the diagnostic workflows of 24 representative Italian institutions performing molecular tests on a series of artificial reference specimens built to mimic routine diagnostic samples. Methods: Sample sets of eight slides from cell blocks of artificial reference specimens harboring exon&nbsp;19 EGFR (epidermal growth factor receptor) p.E746_AT50del, exon&nbsp;2 KRAS (Kirsten rat sarcoma viral oncogene homologue) p.G12C, ROS1 (c-ros oncogene&nbsp;1)-unknown gene fusion, and MET (MET proto-oncogene, receptor tyrosine kinase) Δ exon&nbsp;14 skipping were distributed to each participating institution. Two independent cell block specimens were validated by the University of Naples Federico&nbsp;II before shipment. Methodological and molecular data from reference specimens were annotated. Results: Overall, a median DNA concentration of 3.3&nbsp;ng/μL (range 0.1–10.0&nbsp;ng/μL) and 13.4&nbsp;ng/μL (range 2.0–45.8&nbsp;ng/μL) were obtained with automated and manual technical procedures, respectively. RNA concentrations of 5.7&nbsp;ng/μL (range 0.2–11.9&nbsp;ng/μL) and 9.3&nbsp;ng/μL (range 0.5–18.0&nbsp;ng/μL) were also detected. KRAS exon&nbsp;2 p.G12C, EGFR exon&nbsp;19 p.E736_A750del hotspot mutations, and ROS1 aberrant transcripts were identified in all tested cases, whereas 15 out of 16 (93.7%) centers detected MET exon&nbsp;14 skipping mutation. Conclusions: Optimized technical workflows are crucial in the decision-making strategy of patients with NSCLC. Artificial reference specimens enable optimization of diagnostic workflows for predictive molecular analysis in routine clinical practice

Symptomatic benefits of testosterone treatment in patient subgroups : a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Acknowledgments This work was supported by the UK National Institute for Health and Care Research (NIHR)'s Health Technology Assessment Programme (project number 17/68/01). The views expressed herein are those of the authors and not necessarily those of the National Health Service, the NIHR Health Technology Assessment Programme, or the UK Department of Health and Social Care. The Health Services Research Unit at the University of Aberdeen is funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The Section of Endocrinology and Investigative Medicine at Imperial College London is funded by grants from the Medical Research Council, the Biotechnology and Biological Sciences Research Council, NIHR, an Integrative Mammalian Biology Capacity Building Award, and an FP7-HEALTH-2009-241592 EuroCHIP grant, and is supported by the NIHR Biomedical Research Centre Funding Scheme. WSD is funded by an NIHR Research Professorship. CNJ is funded by an NIHR Post-Doctoral Fellowship. ShB receives NIH research grant funding. The authors are grateful to the clinical and methodological experts and patient partners who contributed to the advisory group for this study.Peer reviewedPublisher PD

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

Background Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. Methods We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. Findings 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60–72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95–7·10]; τ²=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40–2·89]; τ²=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males’ Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). Interpretation In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-mediumterm testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity

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

Crop Updates 2005 - Farming Systems

This session covers forty four papers from different authors: PLENARY 1. 2005 Outlook, David Stephens and Nicola Telcik, Department of Agriculture FERTILITY AND NUTRITION 2. The effect of higher nitrogen fertiliser prices on rotation and fertiliser strategies in cropping systems, Ross Kingwell, Department of Agriculture and University of Western Australia 3. Stubble management: The short and long term implications for crop nutrition and soil fertility, Wayne Pluske, Nutrient Management Systems and Bill Bowden, Department of Agriculture 4. Stubble management: The pros and cons of different methods, Bill Bowden, Department of Agriculture, Western Australia and Mike Collins, WANTFA 5. Effect of stubble burning and seasonality on microbial processes and nutrient recycling, Frances Hoyle, The University of Western Australia 6. Soil biology and crop production in Western Australian farming systems, D.V. Murphy, N. Milton, M. Osman, F.C. Hoyle, L.K Abbott, W.R. Cookson and S. Darmawanto, The University of Western Australia 7. Urea is as effective as CAN when no rain for 10 days, Bill Crabtree, Crabtree Agricultural Consulting 8. Fertiliser (N,P,S,K) and lime requirements for wheat production in the Merredin district, Geoff Anderson, Department of Agriculture and Darren Kidson, Summit Fertilizers 9. Trace element applications: Up-front verses foliar? Bill Bowden and Ross Brennan, Department of Agriculture 10. Fertcare®, Environmental Product Stewardship and Advisor Standards for thee Fertiliser Industry, Nick Drew, Fertilizer Industry Federation of Australia (FIFA) SOIL AND LAND MANAGEMENT 11. Species response to row spacing, density and nutrition, Bill Bowden, Craig Scanlan, Lisa Sherriff, Bob French and Reg Lunt, Department of Agriculture 12. Investigation into the influence of row orientation in lupin crops, Jeff Russell, Department of Agriculture and Angie Roe, Farm Focus Consultants 13. Deriving variable rate management zones for crops, Ian Maling, Silverfox Solutions and Matthew Adams, DLI 14. In a world of Precision Agriculture, weigh trailers are not passé, Jeff Russell, Department of Agriculture 15. Cover crop management to combat ryegrass resistance and improve yields, Jeff Russell, Department of Agriculture and Angie Roe, Farm Focus Consultants 16. ARGT home page, the place to find information on annual ryegrass toxicity on the web, Dr George Yan, BART Pty Ltd 17. Shallow leading tine (SLT) ripper significantly reduces draft force, improves soil tilth and allows even distribution of subsoil ameliorants, Mohammad Hamza, Glen Riethmuller and Wal Anderson, Department of Agriculture PASTURE ANS SUMMER CROP SYSTEMS 18. New annual pasture legumes for Mediteranean farming systems, Angelo Loi, Phil Nichols, Clinton Revell and David Ferris, Department of Agriculture 19. How sustainable are phase rotations with Lucerne? Phil Ward, CSIRO Plant Industry 20. Management practicalities of summer cropping, Andrea Hills and Sally-Anne Penny, Department of Agriculture 21. Rainfall zone determines the effect of summer crops on winter yields, Andrea Hills, Sally-Anne Penny and David Hall, Department of Agriculture 22. Summer crops and water use, Andrea Hills, Sally-Anne Penny and David Hall, Department of Agriculture, and Michael Robertson and Don Gaydon, CSIRO Brisbane 23. Risk analysis of sorgum cropping, Andrea Hills and Sally-Anne Penny, Department of Agriculture, and Dr Michael Robertson and Don Gaydon, CSIRO Brisbane FARMER DECISION SUPPORT AND ADOPTION 24. Variety release and End Point Royalties – a new system? Tress Walmsley, Department of Agriculture 25. Farming system analaysis using the STEP Tool, Caroline Peek and Megan Abrahams, Department of Agriculture 26. The Leakage Calculator: A simple tool for groundwater recharge assessment, Paul Raper, Department of Agriculture 27. The cost of Salinity Calculator – your tool to assessing the profitability of salinity management options, Richard O’Donnell and Trevor Lacey, Department of Agriculture 28. Climate decision support tools, Meredith Fairbanks and David Tennant, Department of Agriculture 29. Horses for courses – using the best tools to manage climate risk, Cameron Weeks, Mingenew-Irwin Group/Planfarm and Richard Quinlan, Planfarm Agronomy 30. Use of seasonal outlook for making N decisions in Merredin, Meredith Fairbanks and Alexandra Edward, Department of Agriculture 31. Forecasts and profits, Benefits or bulldust? Chris Carter and Doug Hamilton, Department of Agriculture 32. A tool to estimate fixed and variable header and tractor depreciation costs, Peter Tozer, Department of Agriculture 33. Partners in grain: ‘Putting new faces in new places’, Renaye Horne, Department of Agriculture 34. Results from the Grower group Alliance, Tracey Gianatti, Grower Group Alliance 35. Local Farmer Group Network – farming systems research opportunities through local groups, Paul Carmody, Local Farmer Group Network GREENHOUSE GAS AND CLIMATE CHANGE 36. Changing rainfall patterns in the grainbelt, Ian Foster, Department of Agriculture 37. Vulnerability of broadscale agriculture to the impacts of climate change, Michele John, CSIRO (formerly Department of Agriculture) and Ross George, Department of Agriculture 38. Impacts of climate change on wheat yield at Merredin, Imma Farré and Ian Foster, Department of Agriculture 39. Climate change, land use suitability and water security, Ian Kininmonth, Dennis van Gool and Neil Coles, Department of Agriculture 40. Nitrous oxide emissions from cropping systems, Bill Porter, Department of Agriculture, Louise Barton, University of Western Australia 41. The potential of greenhouse sinks to underwrite improved land management in Western Australia, Richard Harper and Peter Ritson, CRC for Greenhouse Accounting and Forest Products Commission, Tony Beck, Tony Beck Consulting Services, Chris Mitchell and Michael Hill, CRC for Greenhouse Accounting 42. Removing uncertainty from greenhouse emissions, Fiona Barker-Reid, Will Gates, Ken Wilson and Rob Baigent, Department of Primary Industries - Victoria and CRC for Greenhouse Accounting (CRCGA), and Ian Galbally, Mick Meyer and Ian Weeks, CSIRO Atmospheric Research and CRCGA 43. Greenhouse in Agriculture Program (GIA), Traci Griffin, CRC for Greenhouse Accounting 44. Grains Greenhouse Accounting framework, D. Rodriguez, M. Probust, M. Meyers, D. Chen, A. Bennett, W. Strong, R. Nussey, I. Galbally and M. Howden CONTACT DETAILS FOR PRINCIPAL AUTHOR

Symptomatic benefits of testosterone treatment in patient subgroups: a systematic review, individual participant data meta-analysis, and aggregate data meta-analysis

BACKGROUND: Testosterone replacement therapy is known to improve sexual function in men younger than 40 years with pathological hypogonadism. However, the extent to which testosterone alleviates sexual dysfunction in older men and men with obesity is unclear, despite the fact that testosterone is being increasingly prescribed to these patient populations. We aimed to evaluate whether subgroups of men with low testosterone derive any symptomatic benefit from testosterone treatment. METHODS: We did a systematic review and meta-analysis to evaluate characteristics associated with symptomatic benefit of testosterone treatment versus placebo in men aged 18 years and older with a baseline serum total testosterone concentration of less than 12 nmol/L. We searched major electronic databases (MEDLINE, Embase, Science Citation Index, and the Cochrane Central Register of Controlled Trials) and clinical trial registries for reports published in English between Jan 1, 1992, and Aug 27, 2018. Anonymised individual participant data were requested from the investigators of all identified trials. Primary (cardiovascular) outcomes from this analysis have been published previously. In this report, we present the secondary outcomes of sexual function, quality of life, and psychological outcomes at 12 months. We did a one-stage individual participant data meta-analysis with a random-effects linear regression model, and a two-stage meta-analysis integrating individual participant data with aggregated data from studies that did not provide individual participant data. This study is registered with PROSPERO, CRD42018111005. FINDINGS: 9871 citations were identified through database searches. After exclusion of duplicates and publications not meeting inclusion criteria, 225 full texts were assessed for inclusion, of which 109 publications reporting 35 primary studies (with a total 5601 participants) were included. Of these, 17 trials provided individual participant data (3431 participants; median age 67 years [IQR 60-72]; 3281 [97%] of 3380 aged ≥40 years) Compared with placebo, testosterone treatment increased 15-item International Index of Erectile Function (IIEF-15) total score (mean difference 5·52 [95% CI 3·95-7·10]; τ 2=1·17; n=1412) and IIEF-15 erectile function subscore (2·14 [1·40-2·89]; τ 2=0·64; n=1436), reaching the minimal clinically important difference for mild erectile dysfunction. These effects were not found to be dependent on participant age, obesity, presence of diabetes, or baseline serum total testosterone. However, absolute IIEF-15 scores reached during testosterone treatment were subject to thresholds in patient age and baseline serum total testosterone. Testosterone significantly improved Aging Males' Symptoms score, and some 12-item or 36-item Short Form Survey quality of life subscores compared with placebo, but it did not significantly improve psychological symptoms (measured by Beck Depression Inventory). INTERPRETATION: In men aged 40 years or older with baseline serum testosterone of less than 12 nmol/L, short-to-medium-term testosterone treatment could provide clinically meaningful treatment for mild erectile dysfunction, irrespective of patient age, obesity, or degree of low testosterone. However, due to more severe baseline symptoms, the absolute level of sexual function reached during testosterone treatment might be lower in older men and men with obesity. FUNDING: National Institute for Health and Care Research Health Technology Assessment Programme