Estimating survival in advanced cancer: a comparison of estimates made by oncologists and patients.

PURPOSE: To compare estimates of expected survival time (EST) made by patients with advanced cancer and their oncologists. METHODS: At enrolment patients recorded their "understanding of how long you may have to live" in best-case, most-likely, and worst-case scenarios. Oncologists estimated survival time for each of their patients as the "median survival of a group of identical patients". We hypothesized that oncologists' estimates of EST would be unbiased (~ 50% longer or shorter than the observed survival time [OST]), imprecise (< 33% within 0.67 to 1.33 times OST), associated with OST, and more accurate than patients' estimates of their own survival. RESULTS: Twenty-six oncologists estimated EST for 179 patients. The median estimate of EST was 6.0 months, and the median OST was 6.2 months. Oncologists' estimates were unbiased (56% longer than OST), imprecise (27% within 0.67 to 1.33 times OST), and significantly associated with OST (HR 0.88, 95% CI 0.82 to 0.93, p < 0.01). Only 41 patients (23%) provided a numerical estimate of their survival with 107 patients (60%) responding "I don't know". The median estimate by patients for their most-likely scenario was 12 months. Patient estimates of their most-likely scenario were less precise (17% within 0.67 to 1.33 times OST) and more likely to overestimate survival (85% longer than OST) than oncologist estimates. CONCLUSION: Oncologists' estimates were unbiased and significantly associated with survival. Most patients with advanced cancer did not know their EST or overestimated their survival time compared to their oncologist, highlighting the need for improved prognosis communication training. Trial registration ACTRN1261300128871.

Attitudes and self-reported end-of-life care of Australian and New Zealand intensive care doctors in the context of organ donation after circulatory death.

The incidence of organ donation after circulatory death (DCD) in Australia and New Zealand (ANZ) has steadily increased in recent years. Intensive care doctors are vital to the implementation of DCD and healthcare professionals' attitudes to DCD can influence their participation. In order to determine ANZ intensive care doctors' attitudes to DCD, to explore if demographic characteristics influence attitude to DCD and to assess if attitude to DCD can predict palliative prescription rationale at the end of life of DCD donors, a cross-sectional online survey was distributed to ANZ intensive care doctors and responses collected between 29 April and 10 June 2016. Exploratory factor analysis was used to define various attributes of attitude to DCD. Results were subjected to comparative statistical analyses to examine the relation between demographic data and attitude to DCD. Multiple regression models were used to examine if attitude to DCD could predict intensive care doctors' palliative prescription rationales at the end of life of DCD donors. One hundred and sixty-one intensive care doctors responded to the survey with 69.4% having worked in intensive care for ten years or more. Respondents responded positively to the support of and perceived importance of DCD in helping those who would benefit from the donations (constructive attributes)(mean composite factor score = 3.84, standard deviation [SD] 0.83), they positively perceived that conducive and facilitative orchestration of DCD helps families cope (mean composite factor score = 3.94, SD 0.72) and that they would manage a DCD donor similar to any patient at the end of their life (mean score = 3.94, SD 0.72). Respondents responded negatively to having concerns that the circulatory death of potential DCD donors does not occur within the specified time frame (mean score = 2.28, SD 1.02). There was an association between organ donation professional education courses, familiarity with national guidelines and positive attitudes to certain attributes of attitude to DCD. Regression models demonstrated the attitude to DCD may predict intensive care doctors' palliative medication prescription rationales at the end of life of the DCD donor. Intensive care doctors in ANZ adopt a morally neutral attitude to DCD where they recognise the importance of organ donation, and support and conduct DCD as a part of good end-of-life care.

Organ donation after circulatory death in a university teaching hospital.

Although organ transplantation is well established for end-stage organ failure, many patients die on waiting lists due to insufficient donor numbers. Recently, there has been renewed interest in donation after circulatory death (DCD). In a retrospective observational study we reviewed the screening of patients considered for DCD between March 2007 and December 2012 in our hospital. Overall, 148 patients were screened, 17 of whom were transferred from other hospitals. Ninety-three patients were excluded (53 immediately and 40 after review by donation staff). The 55 DCD patients were younger than those excluded (P=0.007) and they died from hypoxic brain injury (43.6%), intraparenchymal haemorrhage (21.8%) and subarachnoid haemorrhage (14.5%). Antemortem heparin administration and bronchoscopy occurred in 50/53 (94.3%) and 22/55 (40%) of cases, respectively. Forty-eight patients died within 90 minutes and proceeded to donation surgery. Associations with not dying in 90 minutes included spontaneous ventilation mode (P=0.022), absence of noradrenaline infusion (P=0.051) and higher PaO2:FiO2 ratio (P=0.052). The number of brain dead donors did not decrease over the study period. The time interval between admission and death was longer for DCD than for the 45 brain dead donors (5 [3-11] versus 2 [2-3] days; P<0.001), and 95 additional patients received organ transplants due to DCD. Introducing a DCD program can increase potential organ donors without reducing brain dead donors. Antemortem investigations appear to be acceptable to relatives when included in the consent process.

Prevalence and predictors of advance directives in Australia.

BACKGROUND: Advance care planning is regarded as integral to better patient outcomes, yet little is known about the prevalence of advance directives (AD) in Australia. AIM: To determine the prevalence of AD in the Australian population. METHODS: A national telephone survey about estate and advance planning. Sample was stratified by age (18-45 and >45 years) and quota sampling occurred based on population size in each state and territory. RESULTS: Fourteen per cent of the Australian population has an AD. There is state variation with people from South Australia and Queensland more likely to have an AD than people from other states. Will making and particularly completion of a financial enduring power of attorney are associated with higher rates of AD completion. Standard demographic variables were of limited use in predicting whether a person would have an AD. CONCLUSIONS: Despite efforts to improve uptake of advance care planning (including AD), barriers remain. One likely trigger for completing an AD and advance care planning is undertaking a wider future planning process (e.g. making a will or financial enduring power of attorney). This presents opportunities to increase advance care planning, but steps are needed to ensure that planning, which occurs outside the health system, is sufficiently informed and supported by health information so that it is useful in the clinical setting. Variations by state could also suggest that redesign of regulatory frameworks (such as a user-friendly and well-publicised form backed by statute) may help improve uptake of AD.

A checklist for streamlining organ donation after cardiac death.

There is currently a shortage of organ donors to meet the demands of transplantation waiting lists. In recent years there has been renewed interest in donation after cardiac death in order to increase the pool of potential donors. The Organ and Tissue Authority has recently developed a national policy for donation after cardiac death. We describe here a checklist that is used by our hospital-based staff for organ donation which outlines important steps in the donation after cardiac death process.

Continuous hemofiltration for anasarca: recovery of renal function after 71 liters of net ultrafiltration.

We report on a 64-year-old female presenting with anasarca secondary to volume loading in the setting of chronic liver disease, acute on chronic renal failure, circulatory failure and sepsis. Over 37 days, a net negative fluid balance of 71 L was achieved using continuous hemofiltration, with spontaneous recovery of urine output, vasopressor independence and resolution of coagulopathy. This case report underlines the pathophysiological role of tissue edema in the downward spiral of hepato-renal and cardio-renal dysfunction and illustrates that very large volumes of tissue fluid can be safely and effectively removed with continuous renal replacement therapy, thereby permitting recovery of organ function. To our knowledge, there have been no previous reports of such large volume net fluid removal by progressive ultrafiltration in the intensive care unit.

A pilot study of high-adsorption hemofiltration in human septic shock.

BACKGROUND: To compare the hemodynamic and biological effects of high-adsorption continuous veno-venous hemofiltration (CVVH) with standard CVVH in septic shock. METHODS: In a randomized cross-over clinical trial twelve patients with septic shock and multiple organ failure were enrolled at a tertiary intensive care unit. Patients were allocated to either 9 hours of high-adsorption hemofiltration (CVVH with 3 hourly filter change using AN69 hemofilters - 3FCVVH) or 9 hours of standard hemofiltration (CVVH without filter change - 1F-CVVH). RESULTS: Changes in hemodynamic variables, dose of noradrenaline required to maintain a mean arterial pressure greater than 75 mmHg and plasma concentrations of cytokines (IL-6, IL-8, IL-10 and IL-18) were measured. A 9-hour period of 3F-CVVH was associated with greater reduction in noradrenaline dose than a similar period of 1F-CVVH (median reduction: 16 vs. 3.5 microg/min, p=0.036; median percentage reduction: 48.1% vs. 17.5%, p=0.028). Unlike 1F-CVVH, 3F-CVVH was associated with a reduction in the plasma concentration of IL-6, IL-10 and IL-18 at 9 hours and a significant decrease 30 minutes after additional filter changes (IL-6: p<0.01, p<0.01; IL-10: p=0.03, p=0.016 and IL-18: p=0.016, p<0.01, respectively). Both, 3F-CVVH and 1F-CVVH were associated with decreased plasma concentrations of IL-8 at 9 hours (p<0.01, p<0.01, respectively). In a confirmatory ex-vivo experiment IL-6 concentrations substantially decreased during 3F-CVVH (at baseline 511 pg/mL and at end: 21 pg/mL) whereas IL-6 concentrations increased in control blood (at baseline 511 pg/mL and at end: 932 pg/mL). CONCLUSIONS: High-adsorption CVVH appears more effective than standard CVVH in decreasing noradrenaline requirements and plasma concentrations of cytokines in septic shock patients.

Extreme isotopic depletion of nitrogen in New Zealand lithophytes and epiphytes; the result of diffusive uptake of atmospheric ammonia?

Several lichens and the terrestrial alga Trentepohlia were found to have extremely depleted 15N signatures at two sites near the Rotorua geothermal area, New Zealand. Values, typically -20 per thousand, with several extreme cases of -24 per thousand, are more isotopically depleted than any previously quoted delta15N signature for vegetation growing in natural environments. For Trentepohlia, distance from a geothermal source did not affect isotopic signature. A 100-km transect showed that the phenomenon is widespread and the discrimination is not related to substrate N, or to elevation. Rainfall NHx and atmospheric gaseous NH3 (NH3(g)) were shown to be isotopically depleted in the range -1 per thousand to -8 per thousand and could not, of themselves, be responsible for the plant values obtained. A simulation of Trentepohlia thallus was created using an acidified fiberglass mat and was allowed to absorb NH3(g) from the atmosphere. Mats exposed at the geothermal sites and on farm-land showed a significant further depletion of 15N to -17 per thousand. We hypothesize that the extreme isotopic depletion is due to dual fractionation: firstly by the volatilization of NH3(g) from aqueous sources into the atmosphere; secondly by the diffusive assimilation of that NH3(g) into vegetation. We further hypothesize that lithophytes, epiphytes, and higher plants, growing on strongly N-limited substrates, will show this phenomenon more or less, depending on the proportion of diffusively assimilated NH3(g) utilized as a N source. Many of the isotopically depleted delta15N signatures in vegetation, previously reported in the literature, especially epiphytes, may be due to this form of uptake depending on the concentration of atmospheric NH3(g), and the degree of reliance on that form of N.

Using 15N to determine a budget for effluent-derived nitrogen applied to forest.

Using stable N isotopes, the fate of effluent-derived N has been determined within a land based municipal effluent irrigation scheme. Over 900 metric tonnes(t) of effluent-derived N have been applied to 192 ha of production conifer forest near Rotorua (NZ) over the past 11 years. The effluent N has a natural isotopic signal, generated by the treatment process, allowing it to be traced into various components of the system. Using this isotopic signal, a realistic approximation of storage capacity of various components of the system has been generated, including a calculation of the contribution of effluent N exiting the catchment via stream flow. Forest storage accounts for 50% of the applied N with a considerable proportion of that immobilized in wood and soil. The wetland, although not intensively sampled, retains 115 t, (13%) of the applied N. Denitrification, including that occurring within the wetland, accounts for 23 t (3%). Nitrogen isotope data confirm that the rise in NO3 concentrations is directly attributable to effluent N. Currently 88% of NO3-N in the stream is effluent-derived. Using current N isotope values for the stream and extrapolating over the discharge period, export of effluent N via the stream is estimated as 263 t (29%) of the applied N. Overall the forest and wetland ecosystem has intercepted or denitrified 65% of applied N, with 29% lost to the stream, and 50 t (5%) unaccounted for. The forest ecosystem is currently over-supplied with N and a number of management implications flows from these findings. In the long term the continued application of effluent N to the current irrigation area is not sustainable.

A before and after trial of the effect of a high-dependency unit on post-operative morbidity and mortality.

OBJECTIVE: It has been suggested that the availability of a high-dependency unit (HDU), to facilitate graded admission to, and discharge from, an intensive care unit (ICU), might decrease post-operative morbidity. We wished to determine whether the addition of a 4-bed HDU to a tertiary 17-bed ICU facility at a University-affiliated hospital would decrease post-operative morbidity and mortality. PATIENTS AND METHODS: A prospective controlled before-and-after trial was performed with the opening of a 4-bed HDU. Consecutive patients admitted to hospital for major surgery during a 4-month control (pre-HDU) phase and during a 4-month intervention (HDU) phase were studied for the incidence of serious adverse events (SAEs), mortality after major surgery and mean duration of hospital stay. RESULTS: There were 1319 operations performed in 1125 patients during the pre-HDU period and 1369 operations performed in 1127 patients during the HDU period. During the HDU period there was an excess in unscheduled surgery cases (674 during HDU vs. 531 during the pre-HDU period; p < 0.0001). In the pre-HDU period, there were 414 SAEs in 190 patients compared with 456 SAEs in 209 patients during the HDU period (NS). There were no significant changes in any of the individual SAEs measured except for the incidence of post-operative acute pulmonary edema, which increased from 19 cases to 46 during the HDU period (p = 0.028). This increase was associated with a greater number of patients requiring re-intubation (52 vs. 75 cases; p = 0.044). The introduction of an HDU had no effect on mortality (80 deaths vs. 76; NS) and failed to reduce mean hospital length of stay (21.8 vs. 24 days; NS). CONCLUSIONS: The introduction of a 4-bed HDU in a teaching hospital was associated with a marked increase in unscheduled surgery and failed to reduce the incidence of post-operative SAEs, post-operative mortality, and mean duration of hospital stay.

Platelet loss across the hemofilter during continuous hemofiltration.

BACKGROUND: Thrombocytopenia is a common finding in patients in the intensive care unit receiving continuous renal replacement therapy (CRRT). It is unknown if the hemofilter itself contributes to the platelet loss. OBJECTIVE: To measure the direct effect of the hemofilter on platelet counts during CRRT. DESIGN: Prospective, observational study. SETTING: Intensive care unit of a University hospital. PATIENTS: Critically ill patients with acute renal failure receiving CRRT. METHODS: Two samples of blood were drawn simultaneously, pre-filter and post-filter, and analyzed for platelet count. A correction factor was applied to the post-filter platelet count to adjust for the hemoconcentrating effect of net ultrafiltration. RESULTS: Forty-eight sets of paired data from 22 patients were studied. There was a small but significant decrease in mean platelet count across the hemofilter. The mean platelet count drop was 2.32 x 10(9)/L (s.e. 1.06, p = 0.0487, 95% CI (0.01, 4.62)). Blood flow was strongly related to degree of platelet loss, with a decreased loss of 0.07 x 10(9)/L for every ml/min increase in blood flow (p = 0.015). There was no overall decrease in concurrently measured red cell counts across the hemofilter. However, there was a machine-specific affect on red cell loss (p < 0.0001). The total calculated daily platelet loss across the filter was 625 x 10(9) cells. CONCLUSION: The hemofilter may contribute to the thrombocytopenia seen during CRRT, by means of either destruction or retention of platelets during passage. This affect appears attenuated by higher blood flows. This information is useful in the assessment of a low platelet count in patients receiving CRRT.

Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia.

OBJECTIVE: To study the epidemiology, style of management, and outcome of intensive care patients with acute renal failure requiring replacement therapy in Australia. DESIGN: Prospective epidemiologic study. SETTING: Australian adult intensive care units providing acute renal replacement therapy. PATIENTS: Adult intensive care patients with acute renal failure treated with renal replacement therapy. INTERVENTIONS: Demographic and clinical data collection for 3 months. MEASUREMENTS AND MAIN RESULTS: A standardized data collection form for each case of severe acute renal failure was used to collect demographic, biochemical, clinical, and outcome data. Severe acute renal failure affected 299 patients (approximately eight cases per 100,000 adults per year). Among these patients, 99 (33.1%) had impaired baseline renal function, 238 (79.6%) needed mechanical ventilation, and 232 (77.6%) needed continuous vasoactive drug administration. Critical care physicians controlled patient care and renal replacement therapy in 289 cases (96.7%). Critical care nurses performed such therapy alone in 288 (96.3%) cases. Continuous renal replacement therapy was used in 292 (97.7%) patients. There was no nephrological input in 173 (57.8%) cases. Predicted mortality rates were 52.1% by Simplified Acute Physiology Score II, 49.5% by Acute Physiology and Chronic Health Evaluation II score, and 51.9% by an acute renal failure-specific score. Actual mortality rate was 46.8%. Only 25 (15.7%) patients were dialysis-dependent at hospital discharge. Of these patients, 20 (80%) had premorbid chronic impairment of renal function. CONCLUSION: In Australia, critical care physicians and nurses manage severe acute renal failure with limited consultative nephrological input. Renal replacement therapy is continuous and outcomes are satisfactory. Our findings support the view that this approach to management of severe acute renal failure is safe.

The role of papillae during the infection process in the Gunnera-Nostoc symbiosis.

Gunnera manicata L. glands consist of up to nine separate papillae. Surgical removal of papillae showed that more than two papillae were needed for successful infection with Nostoc. Infection occurs only in the enclosed space between adjacent papillae. Dividing Gunnera cells in the enclosed space are the sites of infection.

An extracorporeal membrane oxygenation-based approach to cardiogenic shock in an older population.

BACKGROUND: We investigated the efficacy of an integrated system of advanced supportive care based on extracorporeal membrane oxygenation (ECMO) in older patients with an estimated mortality of more than 90% to establish whether its use is justifiable. METHODS: Treatment was provided by cardiac surgeons and critical care physicians and included the following key elements: (1) ECMO, (2) early application of continuous venovenous hemofiltration, (3) inhaled nitric oxide, (4) maintenance of perfusion pressure with norepinephrine, (5) maintenance of pulmonary blood flow by ventricular filling with intravenous colloids, (6) avoidance of early postoperative anticoagulation, (7) frequent use of transesophageal echocardiography, and (8) low tidal volume ventilation. Demographic features, intraoperative details, postoperative course, ECMO weaning rate, morbidity, survival to hospital discharge, and the quality of life of survivors were recorded. RESULTS: Seventeen consecutive patients (median age, 69 years) with refractory cardiogenic shock were studied. The median duration of ECMO was 86 hours (20 to 201 hours). Eleven patients (65%) were successfully weaned from ECMO. Seven patients (41%) survived to discharge. The major causes of morbidity were bleeding and leg ischemia. All patients who survived to discharge were alive and well at follow-up (median, 21 months) and reported a satisfactory quality of life. CONCLUSIONS: An ECMO-based approach can be used with acceptable results in the treatment of refractory cardiogenic shock, even in older patients.

Early and intensive continuous hemofiltration for severe renal failure after cardiac surgery.

BACKGROUND: The aim of this study was to test whether early and intensive use of continuous venovenous hemofiltration (CVVH) achieved a better than predicted outcome in patients with severe acute renal failure undergoing cardiac operations, and whether a simple and yet accurate model could be developed to predict their outcome before starting CVVH. METHODS: Medical record analysis with collection of demographic, clinical, and outcome information was used. RESULTS: Sixty-five consecutive patients were treated with early and intensive CVVH (mean operation to CVVH time, 2.38 days; pump-controlled ultrafiltration rate, 2 L/h) after coronary artery bypass grafting (56.9%), single valve procedure (16.9%), or combined operations (26.2%). In 32.3% of patients, intraaortic balloon counterpulsation was required and 20% of patients were emergencies. Sustained hypotension despite inotropic and vasopressor support occurred in 40% of patients and prolonged mechanical ventilation in 58.5%. Using an outcome prediction score specific for acute renal failure, the predicted risk of death was 66%. Actual mortality was 40% (p = 0.003). Using multivariate logistic regression analysis and neural network analysis, patient outcome could be predicted with good levels of accuracy (receiver operating characteristic 0.89 and 0.9, respectively). CONCLUSIONS: Early and aggressive CVVH is associated with better than predicted survival in severe acute renal failure after cardiac operations. Using readily available clinical data, the outcome of such patients can be predicted before the implementation of CVVH.

A prospective, multicenter study of the epidemiology, management, and outcome of severe acute renal failure in a "closed" ICU system.

The safety and effectiveness of "closed" intensive care units (ICUs) are highly controversial. The epidemiology and outcome of acute renal failure (ARF) requiring replacement therapy (severe ARF) within a "closed" ICU system are unknown. Accordingly, we performed a prospective 3-mo multicenter observational study of all Nephrology Units and ICUs in the State of Victoria (all "closed" ICUs), Australia, and focused on the epidemiology, treatment, and outcome of patients with severe ARF. We collected demographic, clinical, and outcome data using standardized case report forms. Nineteen ward patients and 116 adult ICU patients had severe ARF (13.4 cases/100, 000 adults/yr). Among the ICU patients with severe ARF, 37 had impaired baseline renal function, 91 needed ventilation, and 95 needed vasoactive drugs. Intensivists controlled patient care in all cases. Continuous renal replacement therapy (CRRT) was used in 111 of the ICU patients. Nephrological opinion was sought in only 30 cases. Predicted mortality was 59.6%. Actual mortality was 49.2%. Only 11 ICU survivors were dialysis dependent at hospital discharge. In the state of Victoria, Australia, intensivists manage severe ARF within a "closed" ICU system. Renal replacement is typically continuous and outcomes compare favorably with those predicted by illness severity scores. Our findings support the safety and efficacy of a "closed" ICU model of care.