Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

The impact of e-learning champions on embedding e-learning

This report looks at the use of e-learning champions as a change management strategy and outlines common activities and guidelines adopted by e-learning champions to successfully facilitate the uptake of e-learning within their organisation. It confirms that successful e-learning champions possess a defined set of characteristics, including: Credibility – A champion is skilled in e-learning; shares knowledge, skills and resources; is passionate and tenacious; communicates well; is client focused; and problem solves. &nbsp; Support – A champion provides tailored, educationally sound solutions; encourages teachers/trainers to explore e-learning; supports teachers/trainers one-on-one; and reviews and adapts as required. &nbsp; Influence – A champion builds capable e-learning teams; creates communities of practice; facilitates peer-to-peer learning; recognises and showcases achievements; and nurtures influential advocates. &nbsp; Commitment – A champion makes e-learning part of the strategic plan; ensures e-learning is appropriately resourced; makes e-learning part of teacher/trainer performance plans; and provides opportunities and time to learn, experiment and review e-learning tools and products. &nbsp; The study has a firm message for employers looking to harness the benefits of e-learning, warning: E-learning champions are often better recognised for their work outside of their organisation than within it.&nbsp; Champions of e-learning cannot alone embed e-learning in their organisation, industry or community. To sustain e-learning, managers and policy makers must assist and build organisational cultures and work processes that support innovation and the work of e-learning champions.&nbsp

Conceptual Development of a National Volcanic Hazard Model for New Zealand

We provide a synthesis of a workshop held in February 2016 to define the goals, challenges and next steps for developing a national probabilistic volcanic hazard model for New Zealand. The workshop involved volcanologists, statisticians, and hazards scientists from GNS Science, Massey University, University of Otago, Victoria University of Wellington, University of Auckland, and University of Canterbury. We also outline key activities that will develop the model components, define procedures for periodic update of the model, and effectively articulate the model to end-users and stakeholders. The development of a National Volcanic Hazard Model is a formidable task that will require long-term stability in terms of team effort, collaboration, and resources. Development of the model in stages or editions that are modular will make the process a manageable one that progressively incorporates additional volcanic hazards over time, and additional functionalities (e.g., short-term forecasting). The first edition is likely to be limited to updating and incorporating existing ashfall hazard models, with the other hazards associated with lahar, pyroclastic density currents, lava flow, ballistics, debris avalanche, and gases/aerosols being considered in subsequent updates

Treatment of Lupus Nephritis with Abatacept: The Abatacept and Cyclophosphamide Combination Efficacy and Safety Study

OBJECTIVE: To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis. An additional exploratory objective was to assess the potential of abatacept to induce ‘clinical tolerance’, defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. METHODS: Patients (n=134) with active lupus nephritis were studied in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus regimen of low-dose cyclophosphamide followed by azathioprine. The primary efficacy outcome was the frequency of complete response (CR) at week 24. Thereafter, patients who met either complete or partial response criteria continued blinded treatment through week 52. During this phase of the study, subjects in the abatacept treatment group who had achieved CR status at week 24 discontinued immunosuppressive therapy other than prednisone (10 mg/d). RESULTS: There were no statistically significant differences between groups with respect to the primary outcome or any of the secondary outcomes, including measures of safety. Thirty-three percent of subjects in the treatment group and 31% of subjects in the control group achieved CR status at week 24. Fifty percent of subjects in the treatment group who met CR criteria and therefore discontinued immunosuppressive therapy at week 24 maintained their CR status through week 52. CONCLUSION: The addition of abatacept to a regimen of cyclophosphamide followed by azathioprine did not improve the outcome of lupus nephritis at either 24 or 52 weeks. No worrisome safety signals were encountered

Reporter

Issue Subtitle: "Ushi Patel: A Giant Amongst Giants

Animal population decline and recovery after severe fire: Relating ecological and life history traits with expert estimates of population impacts from the Australian 2019-20 megafires

Catastrophic megafires can increase extinction risks identifying species priorities for management and policy support is critical for preparing and responding to future fires. However, empirical data on population loss and recovery post-fire, especially megafire, are limited and taxonomically biased. These gaps could be bridged if species' morphological, behavioural, ecological and life history traits indicated their fire responses. Using expert elicitation that estimated population changes following the 2019–20 Australian megafires for 142 terrestrial and aquatic animal species (from every vertebrate class, one invertebrate group), we examined whether expert estimates of fire-related mortality, mortality in the year post-fire, and recovery trajectories over 10 years/three generations post-fire, were related to species traits. Expert estimates for fire-related mortality were lower for species that could potentially flee or shelter from fire, and that associated with fire-prone habitats. Post-fire mortality estimates were linked to diet, diet specialisation, home range size, and susceptibility to introduced herbivores that damage or compete for resources. Longer-term population recovery estimates were linked to diet/habitat specialisation, susceptibility to introduced species species with slower life histories and shorter subadult dispersal distances also had lower recovery estimates. Across animal groups, experts estimated that recovery was poorest for species with pre-fire population decline and more threatened conservation status. Sustained management is likely needed to recover species with habitat and diet specialisations, slower life histories, pre-existing declines and threatened conservation statuses. This study shows that traits could help inform management priorities before and after future megafires, but further empirical data on animal fire response is essential