Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Renal supportive and palliative care: position statement.

Since the introduction of haemodialysis in the management of acute kidney injury in the 1940s and for chronic kidney disease (CKD) in the 1960s dialysis has become one of the most successful advances in medical technology, with almost 11 000 patients currently receiving dialysis in Australia and almost 2500 in New Zealand. Like all medical technologies, its place continues to evolve. For a time, dialysis was seen as a treatment best delivered only to younger patients without diabetes; today the greatest uptake of dialysis is in patients over age 65 and the most common cause of needing dialysis is diabetes. Along with these extended criteria for dialysis, that have evolved over many years, has come the recognition that the older dialysis patient often has considerable co-morbidity and frailty, that time spent on dialysis is not always beneficial to these patients and that their overall prognosis is considerably worse than their younger counterparts. CARI guidelines recommend that ‘an expectation of survival with an acceptable quality of life’ is a useful starting point for recommending dialysis

Soft actors in private regulation processes: challenger organizations’ direct and indirect work in shaping future environmental accounting standards

International audienc

Soft actors in private regulation processes: challenger organizations’ direct and indirect work in shaping future environmental accounting standards

International audienc

What a patient wants: A consumer perspective of kidney supportive care

Aim To evaluate benefits patients and carers derive from a kidney supportive care (KSC) program, integrating renal and palliative medicine. Background Patient and carer perspectives are vital for developing healthcare strategies that are equitable, accessible, effective and patient-centred. This is especially important in the context of end-stage kidney disease (ESKD), where treatment options can be extremely burdensome while, in many cases, providing little long-term benefit. KSC is emerging as an effective way to care for patients with ESKD—whether on dialysis or not—who need help with symptom management, advance care planning and/or complex decision-making around dialysis options. Methods Patient and carer satisfaction with a new KSC program in the north of Brisbane and symptom scores were assessed using self-reported questionnaires. Place of death data were collected from medical records. To obtain detailed information about patient and carer perceptions of the program and their healthcare needs, semi-structured interviews based on the Consolidated Framework for Implementation Research were conducted with 10 patients and 5 carers receiving KSC. Results KSC patients and carers were highly satisfied with the program (96% and 91% satisfaction, respectively). Reasons for this included feeling supported, having enough time for detailed discussions and the program’s focus on wellbeing rather than biochemical markers. Patients and carers reported that they valued receiving care that they perceived to be tailored to them and their circumstances. Overall symptom burden decreased in 69% of those who had attended >1 KSC visit. Among patients who died, 75% died in their preferred final place of care. Conclusions Patients and carers receiving KSC derived benefits including improved symptom control and self-determination, and valued the quality of care they received