Projecting the future: modelling Australian dialysis prevalence 2021–30

To project the prevalence of people receiving dialysis in Australia for 2021–30 to inform service planning and health policy. Methods. Estimates were based on data from 2011 to 2020 from the Australia & New Zealand Dialysis & Transplant (ANZDATA) Registry and the Australian Bureau of Statistics. We projected dialysis and functioning kidney transplant recipient populations for the years 2021–30. Discrete-time, non-homogenous Markov models were built on probabilities for transition between three mutually exclusive states (Dialysis, Functioning Transplant, Death), for five age groups. Two scenarios were employed – stable transplant rate vs a continued increase – to assess the impact of these scenarios on the projected prevalences. Results. Models projected a 22.5–30.4% growth in the dialysis population from 14 554 in 2020 to 17 829 (‘transplant growth’) – 18 973 (‘transplant stable’) by 2030. An additional 4983–6484 kidney transplant recipients were also projected by 2030. Dialysis incidence per population increased and dialysis prevalence growth exceeded population ageing in 40–59 and 60–69 year age groups. The greatest dialysis prevalence growth was seen among those aged ≥70 years. Conclusion. Modelling of the future prevalence of dialysis use highlights the increasing demand on services expected overall and especially by people aged ≥70 years. Appropriate funding and healthcare planning must meet this demand.Dominic Keuskamp, Christopher E. Davies, Georgina L. Irish, Shilpanjali Jesudason and Stephen P. McDonal

Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo

Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture.Fil: Samarage, Chaminda R.. Monash University; AustraliaFil: White, Melanie D.. Monash University; AustraliaFil: Alvarez, Yanina Daniela. Monash University; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fierro González, Juan Carlos. Monash University; AustraliaFil: Henon, Yann. Monash University; AustraliaFil: Jesudason, Edwin C.. National Health Service Scotland; Reino UnidoFil: Bissiere, Stephanie. Monash University; Australia. Institute of Molecular and Cell Biology; SingapurFil: Fouras, Andreas. Monash University; AustraliaFil: Plachta, Nicolas. Monash University; Australia. Institute of Molecular and Cell Biology; Singapu

Recruitment of men to a multi-centre diabetes prevention trial: an evaluation of traditional and online promotional strategies

Background: Effective interventions are required to prevent the current rapid increase in the prevalence of Type 2 diabetes. Clinical trials of large-scale interventions to prevent Type 2 diabetes are essential but recruitment is challenging and expensive, and there are limited data regarding the most cost-effective and efficient approaches to recruitment. This paper aims to evaluate the cost and effectiveness of a range of promotional strategies used to recruit men to a large Type 2 diabetes prevention trial. Methods: An observational study was conducted nested within the Testosterone for the Prevention of Type 2 Diabetes (T4DM) study, a large, multi-centre randomised controlled trial (RCT) of testosterone treatment for the prevention of Type 2 diabetes in men aged 50–74 years at high risk of developing diabetes. Study participation was promoted via mainstream media—television, newspaper and radio; direct marketing using mass mail-outs, publicly displayed posters and attendance at local events; digital platforms, including Facebook and Google; and online promotions by community organisations and businesses. For each strategy, the resulting number of participants and the direct cost involved were recorded. The staff effort required for each strategy was estimated based on feedback from staff. Results: Of 19,022 men screened for the study, 1007 (5%) were enrolled. The most effective recruitment strategies were targeted radio advertising (accounting for 42% of participants), television news coverage (20%) and mass mail-outs (17%). Other strategies, including radio news, publicly displayed posters, attendance at local events, newspaper advertising, online promotions and Google and Facebook advertising, each accounted for no more than 4% of enrolled participants. Recruitment promotions cost an average of AU$594 per randomised participant. The most cost-effective paid strategy was mass mail-outs by a government health agency (AU$745 per participant). Other paid strategies were more expensive: mail-out by general practitioners (GPs) (AU$1104 per participant), radio advertising (AU$1081) and newspaper advertising (AU$1941). Conclusion: Radio advertising, television news coverage and mass mail-outs by a government health agency were the most effective recruitment strategies. Close monitoring of recruitment outcomes and ongoing enhancement of recruitment activities played a central role in recruitment to this RCT.Karen Bracken, Wendy Hague, Anthony Keech, Ann Conway, David J. Handelsman, Mathis Grossmann, David Jesudason, Bronwyn Stuckey, Bu B. Yeap, Warrick Inder, Carolyn Allan, Robert McLachlan, Kristy P. Robledo and Gary Witter

Contrasting Expression of Canonical Wnt Signaling Reporters TOPGAL, BATGAL and Axin2LacZ during Murine Lung Development and Repair

Canonical Wnt signaling plays multiple roles in lung organogenesis and repair by regulating early progenitor cell fates: investigation has been enhanced by canonical Wnt reporter mice, TOPGAL, BATGAL and Axin2LacZ. Although widely used, it remains unclear whether these reporters convey the same information about canonical Wnt signaling. We therefore compared beta-galactosidase expression patterns in canonical Wnt signaling of these reporter mice in whole embryo versus isolated prenatal lungs. To determine if expression varied further during repair, we analyzed comparative pulmonary expression of beta-galactosidase after naphthalene injury. Our data show important differences between reporter mice. While TOPGAL and BATGAL lines demonstrate Wnt signaling well in early lung epithelium, BATGAL expression is markedly reduced in late embryonic and adult lungs. By contrast, Axin2LacZ expression is sustained in embryonic lung mesenchyme as well as epithelium. Three days into repair after naphthalene, BATGAL expression is induced in bronchial epithelium as well as TOPGAL expression (already strongly expressed without injury). Axin2LacZ expression is increased in bronchial epithelium of injured lungs. Interestingly, both TOPGAL and Axin2LacZ are up regulated in parabronchial smooth muscle cells during repair. Therefore the optimal choice of Wnt reporter line depends on whether up- or down-regulation of canonical Wnt signal reporting in either lung epithelium or mesenchyme is being compared

Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol.

Background: This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods: 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings: 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation: Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females. Funding: National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation

Democratization and foreign policy in Southeast Asia: the case of the ASEAN Inter-Parliamentary Myanmar Caucus

This is an Author's Accepted Manuscript of an article published in Cambridge Review of International Affairs Vol. 22, Iss. 3, 2009 as published in the CAMBRIDGE REVIEW OF INTERNATIONAL AFFAIRS, 2009, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/09557570903104008

Genetic epidemiology of SARS-CoV-2 transmission in renal dialysis units - a high risk community-hospital interface

OBJECTIVES: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium. METHODS: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations. RESULTS: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated. CONCLUSIONS: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings

What is the recovery rate and risk of long-term consequences following a diagnosis of COVID-19?:A harmonised, global longitudinal observational study protocol

Introduction: Very little is known about possible clinical sequelae that may persist after resolution of acute COVID-19. A recent longitudinal cohort from Italy including 143 patients followed up after hospitalisation with COVID-19 reported that 87% had at least one ongoing symptom at 60-day follow-up. Early indications suggest that patients with COVID-19 may need even more psychological support than typical intensive care unit patients. The assessment of risk factors for longer term consequences requires a longitudinal study linked to data on pre-existing conditions and care received during the acute phase of illness. The primary aim of this study is to characterise physical and psychosocial sequelae in patients post-COVID-19 hospital discharge. Methods and analysis: This is an international open-access prospective, observational multisite study. This protocol is linked with the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) and the WHO’s Clinical Characterisation Protocol, which includes patients with suspected or confirmed COVID-19 during hospitalisation. This protocol will follow-up a subset of patients with confirmed COVID-19 using standardised surveys to measure longer term physical and psychosocial sequelae. The data will be linked with the acute phase data. Statistical analyses will be undertaken to characterise groups most likely to be affected by sequelae of COVID-19. The open-access follow-up survey can be used as a data collection tool by other follow-up studies, to facilitate data harmonisation and to identify subsets of patients for further in-depth follow-up. The outcomes of this study will inform strategies to prevent long-term consequences; inform clinical management, interventional studies, rehabilitation and public health management to reduce overall morbidity; and improve long-term outcomes of COVID-19. Ethics and dissemination: The protocol and survey are open access to enable low-resourced sites to join the study to facilitate global standardised, longitudinal data collection. Ethical approval has been given by sites in Colombia, Ghana, Italy, Norway, Russia, the UK and South Africa. New sites are welcome to join this collaborative study at any time. Sites interested in adopting the protocol as it is or in an adapted version are responsible for ensuring that local sponsorship and ethical approvals in place as appropriate. The tools are available on the ISARIC website (www.isaric.org)

Long Covid in adults discharged from UK hospitals after Covid-19 : a prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol

Funding: This work is supported by grants from: the National Institute for Health Research (NIHR) [award CO-CIN-01], the Medical Research Council [grant MC_PC_19059], the Imperial Biomedical Research Centre (NIHR Imperial BRC, grant P45058), the Health Protection Research Unit (HPRU) in Respiratory Infections at Imperial College London and NIHR HPRU in Emerging and Zoonotic Infections at University of Liverpool, both in partnership with Public Health England, [NIHR award 200907], Wellcome Trust and Department for International Development [215091/Z/18/Z], and the Bill and Melinda Gates Foundation [OPP1209135], and Liverpool Experimental Cancer Medicine Centre (Grant Reference: C18616/A25153), NIHR Biomedical Research Centre at Imperial College London [IS-BRC-1215-20013], EU Platform for European Preparedness Against (Re-) emerging Epidemics 1 [FP7 project 602525] and NIHR Clinical Research Network for providing infrastructure support for this research. LT is a Wellcome Trust clinical career development fellow, supported by grant number 205228/Z/16/Z. This research was funded in part, by the Wellcome Trust. PJMO is supported by a NIHR Senior Investigator Award [award 201385].Background : This study sought to establish the long-term effects of Covid-19 following hospitalisation. Methods : 327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L). Findings : 55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age. Interpretation : Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.Publisher PDFPeer reviewe