An Davies

Early Lung Transplantation Success Utilizing Controlled Donation After Cardiac Death Donors

Donation‐after cardiac death (DCD) donor organs have potential to significantly alleviate the shortage of transplantable lungs. However, only limited data so far describes DCD lung transplantation (LTx) techniques and results. This study aims to describe the Alfred Hospitals early and intermediate outcomes following DCD donor LTx. Following careful experimentation and consultation DCD guidelines were created to utilize Maastricht category III lung donors from either the ICU or operating room(OR), with a warm ischemic time(WIT) of <60 min. Between May 2006 and December 2007, 22 referred DCD donors led to 11 attempted retrievals after withdrawal, resulting in 8 actual bilateral LTx (2 donors did not arrest in prescribed period and 1 donor had nonacceptable lungs). ICU WIT = 38.4 min (range 20–54, OR WIT = 12.7 min (11–15), p < 0.05. Post‐LTx, 1 pulmonary hypertensive patient required ECMO for PGD3. The mean group pO2/FiO2 ratio at 24 hours was 307.7 (240–507) with an ICU stay of 9.5 days (2–21) and ward stay of 21.5 days (11–76). All 8 survive at a mean of 311 days (10–573) with good performance status and lung function. In conclusion, the use of Maastricht category III lungs for human LTx is associated with acceptable early clinical outcomes.

A community-based exercise programme to improve functional ability in people with Alzheimer's disease: A randomized controlled trial

RATIONALE Dementia is a common neurodegenerative condition in older age associated with functional decline across multiple domains. This decline impacts not only on the person with dementia, but also on their informal carers and health and aged care systems. With the number of people with dementia rapidly increasing and few effective treatments, there is now a critical need for interventions to improve functional ability in those with the condition. AIMS AND OBJECTIVE This study assesses the effectiveness of a community-based home exercise programme in improving cognitive and physical function and independence in activities of daily living (ADL) in people with Alzheimers disease, the most common form of dementia. METHODS In a 4-month randomized controlled trial, 40 community-dwelling patients diagnosed with Alzheimers disease and their informal carers were randomly allocated to either the treatment (exercise plus usual treatment) or control (usual treatment) group. The exercise programme consisted of daily exercises and walking under the supervision of their carer. Patients were assessed at baseline and 4-months follow-up by a blinded assessor on primary outcome measures of cognitive and physical function and ADL using standardized assessment scales. RESULTS Sixteen men and 24 women diagnosed with Alzheimers disease participated in the study. They had a mean age of 74.1 years (range 51-89) and a mean Mini Mental State Examination score of 22.0 (range 10-28), indicating mild to moderate dementia. At 4-months follow-up, patients who exercised, compared with controls, had improved cognition (increased Mini Mental State Examination scores by 2.6 points, p < 0.001), better mobility (2.9 seconds faster on Timed Up and Go, p = 0.004) and increased Instrumental Activities of Daily Living scores by 1.6 (p = 0.007). CONCLUSION This study suggests that participation in a community-based exercise programme can improve cognitive and physical function and independence in ADL in people with Alzheimers disease.

Early decompressive craniectomy for patients with severe traumatic brain injury and refractory intracranial hypertension—A pilot randomized trial

PURPOSE The aims of this study were to test the feasibility and to assess potential recruitment rates in a pilot study preliminary to a phase III randomized trial of decompressive craniectomy surgery in patients with diffuse traumatic brain injury (TBI) and refractory intracranial hypertension. MATERIALS AND METHODS A study protocol was developed, inclusion and exclusion criteria were defined, and a standardized surgical technique was established. Neurologic outcomes were assessed 6 months after injury with a validated structured questionnaire and a single trained assessor blind to treatment group. RESULTS During the 8-month pilot study at a level 1 trauma center in Melbourne, Australia, 69 intensive care patients with severe TBI were assessed for inclusion. Six patients were eligible, and 5 (8%) were randomized. Six months after injury, 100% of patients received outcome assessments. Key improvements to the multicenter Decompressive Craniectomy study protocol were enabled by the pilot study. CONCLUSIONS In patients with severe TBI and refractory intracranial hypertension, the frequency of favorable neurologic outcomes (independent living) was low and similar to predicted values (40% favorable). A future multicenter phase III trial involving 18 neurotrauma centers with most sites conservatively recruiting at just 25% of the pilot study rate would require at least 5 years to achieve an estimated 210-patient sample size. Collaboration with neurotrauma centers in countries other than Australia and New Zealand would be required for such a phase III trial to be successful.

Density of Microbial Colonization on External and Internal Surfaces of Concurrently Placed Intravascular Devices

BACKGROUND Intravascular devices provide essential vascular access for management of critically ill patients but can be associated with bloodstream infections. OBJECTIVES To determine colonization rates in segments of concurrently placed peripheral arterial, nontunnelled short-term central venous catheters and peripherally inserted central catheters and the pattern of heaviest colonization when the catheters are removed. METHODS A prospective study was conducted on inpatients with intravascular devices in place for 9 days or more. At removal, each catheter was cut into 3 segments, and each segment was cultured separately. The density of colonization on external and internal surfaces of each segment was compared by estimating odds ratios by repeated-measures ordinal logistic regression. RESULTS A total of 48 peripheral arterial, 135 central venous, and 106 peripherally inserted central catheters were obtained from 289 patients. Colonization was greatest at the proximal external segment of all catheters. On the external surface, colonization was lower on the middle (odds ratio, 0.70; P < .001) and distal (odds ratio, 0.56; P < .001) segments than on the proximal segments. On the internal surface, colonization was lower on the proximal (odds ratio, 0.39; P < .001), middle (odds ratio, 0.30; P < .001), and distal (odds ratio, 0.31; P < .001) segments than on the external proximal segments. This trend was similar for all catheter types. CONCLUSION Colonization of intravascular devices was heaviest on proximal segments.

Development of an experimental model of maternal allergic asthma during pregnancy

We studied the effects of preconceptional allergen sensitisation and repeated airway allergen challenges during pregnancy on maternal immune and airway functions during pregnancy, and maternal, fetal and placental phenotype in late pregnancy in sheep. This protocol induced maternal responses consistent with an allergic asthmatic phenotype. During pregnancy, lung resistance and the eosinophil influx induced by allergen challenges increased progressively in allergic sheep, and in late pregnancy airway smooth muscle content was greater in allergic than control ewes. Effects on fetal growth and development were consistent with those of maternal asthma in humans. Maternal allergic asthma decreased relative fetal weight by 12%, reduced fetal lung expression of surfactant protein B, and altered placental morphology. This provides an animal model in which to identify mechanisms underlying fetal effects of maternal asthma in pregnancy, including fetal physiological responses to exacerbations, and to evaluate responses to clinically used treatments and novel interventions.

The effect of veno-venous ECMO on the pharmacokinetics of Ritonavir, Darunavir, Tenofovir and Lamivudine

Introduction To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno‐venous ECMO (VV ECMO). Methods Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre‐emptive dose adjustments. Published population PK models were used to simulate plasma concentration profiles for the drugs. The population prediction and the observed plasma concentrations were then overlaid with the expected drug profiles using the individual Bayesian post‐hoc parameter estimates. Results Following dose adjustments, the PK profiles of Ritonavir, Darunavir and Tenofovir fell within the expected range and appeared similar to the population prediction, although slightly different for Ritonavir. The observed data for Lamivudine and its PK profile were completely different from the data available in the literature. Conclusions To our knowledge, this is the first study reporting the PK profile of ART drugs during ECMO therapy. Based on our results, dose adjustment of ART drugs while on VV ECMO may be advisable. Further study of the PK profile of Lamivudine is required. HighlightsThis is the first study investigating the PK profile of antiretrovirals during ECMO.Population‐based predications were compared with plasma drug concentrations on ECMO.Ritonavir, Darunavir and Tenofovir were in the expected range after dose adjustments.The observed data for Lamivudine was completely different from predictions.We conclude that dose adjustments of ART drugs while on VV‐ECMO may be advisable.

A community-based exercise program to improve cognitive function in people with mild to moderate Alzheimer's disease: Feasibility and safety study

in future research and facilitate reporting on service performance issues. This project will be undertaken over the next 12 months. Results: There are likely to be a number of benefits flowing from this project for clinical staff and researchers interested in aged care and dementia. These include the convenience of a single point of access to comprehensive data describing service performance, patients’ clinical information including assessment results and summary information for specific clinical research projects. This information may be provided in routine reports and on an ‘‘on demand’’ basis to appropriate staff. Conclusions: This exciting project will place these clinical services and WDREC researchers in a position to be able to conduct a variety of valuable clinical research projects that are likely to enhance service provision and improve the care of older adults in the future. Background: Canine Cognitive Dysfunction (CCD) is a progressive disorder that affects senior dogs and includes deficits in learning and memory, development of b-amyloid plaques and deficits in dopamine and acetylcholine levels. There is, however, no consensus on a method for formal diagnosis for CCD in community-dwelling animals, and how CCD differs from normal canine ageing has yet to established. Methods: Owners of dogs 8 years were asked to complete an 83 item survey, designed to quantify the frequency and change in behaviors related to general health, eating and drinking, activity, instrumental behaviors, continence, fears, phobias and aggression over a 6 month period. An online version was distributed to veterinary schools internationally. A hard copy of the survey was also distributed through Dogs Life magazine. Results: 957 responses were received, of which 18 dogs were reported by owners to have a veterinary diagnosis of dementia (DEM). 10 behaviours were found to significantly distinguish DEM dogs after correction for age. An algorithmic diagnosis of query CCD (qCCD) was developed that agreed with veterinary diagnosis with an overall diagnostic accuracy of 90%. CCD based on this definition increased exponentially with age after 10 years. Conclusions: A formal scale for diagnosis and assessment of CCD is presented with clinical, cross sectional and longitudinal validity. Its use will aid diagnosis and management of canine ‘dementia’ and will also aid translational research between transgenic rodent models and human clinical trials.