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

A selective review of possible neurological etiologies of schizophrenia

Attempts to research the biological correlates and etiology of schizophrenia have suffered from a lack of clear diagnostic differentiation. Proposed classifications of acute/chronic, paranoid/nonparanoid, and negative symptom/positive symptom lack sufficient discrimination between subgroups. Recent research on biochemical neurotransmission, particularly in the activity of dopamine and neuropeptides, in conjunction with neuropathological research into structural abnormalities, has led to a 2-syndrome hypothesis. The viral theory has recently been rejuvenated in light of the discovery of genetically transmitted retroviruses and confirmation of the season of birth effect in the Northern Hemisphere. Unfortunately, problems of neuroleptic drugs effects, the role of secondary symptoms, significant overlap between groups, and inconsistent results continue to confound comprehensive interpretation

Characteristics of the Frequent Nightmare Sufferer

Previous research has found that persons who experience frequent nightmares score highly on scales that measure psychotic symptomatology. Neurotic symptoms have also been implicated as correlates of nightmare frequency. In this study, 30 adult lifelong nightmare sufferers were compared with 30 control subjects, matched for age, sex, and socioeconomic status. Subjects were asked to record all dreams for 1 month and to complete the Minnesota Multiphasic Personality Inventory (MMPI) and the Eysenck Personality Questionnaire (EPQ). Nightmare subjects scored significantly higher on the EPQ Neuroticism scale and on 8 MMPI clinical scales than did the control group. These scales also best discriminated between the groups in a direct discriminant analysis. The results are interpreted as a reflection of global maladjustment rather than of specific psychotic symptomatology

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

Complex prescribing in chronic kidney disease: role of the renal pharmacist in kidney supportive care in uncovering hydralazine-related lupus

Background: Herein we describe the presentation of drug-induced lupus in an 89-year-old woman with end-stage kidney disease (estimated glomerular filtration rate (eGFR) 11\ua0mL/min per 1.73\ua0m) who had chosen a conservative non-dialysis pathway of care, and highlight the role of a pharmacist in identifying drug-related problems. Clinical details: Among numerous health conditions, the patient had systemic lupus erythematosus (SLE) that had previously responded to hydroxychloroquine, which had been ceased. Hydralazine was subsequently commenced to control the patient's blood pressure. The combination of ceasing the medicine that controlled the patient's SLE and commencing a medicine that accumulates in patients with reduced renal function and can precipitate SLE resulted in a reactivation of the patient's disease. Outcomes: The pharmacist was pivotal in uncovering the timeline of medication changes and assisting in identifying SLE reactivation. Cessation of the patient's hydralazine and recommencing hydroxychloroquine resulted in the resolution of the symptoms. Conclusion: This case presents the value of an interdisciplinary approach to patient directed symptoms, when prescribing in the very complex clinical context of multiple comorbid conditions for patients with severely reduced renal function