Mycobacterium bovis (M. bovis), a member of the Mycobacterium tuberculosis complex (MTBC), is the causative agent of bovine TB (bTB) in animals. Spread occurs through inhalation or ingestion of ...bacilli transmitted from infected individuals. Early and accurate detection of infected African buffaloes shedding M. bovis is essential for interrupting transmission. In this pilot study, we determined if MTBC DNA could be detected in M. bovis infected buffalo oronasal secretions using a molecular transport media (PrimeStore MTM) with oronasal swabs and a rapid qPCR assay (Xpert MTB/RIF Ultra). Bovine TB test-positive buffaloes were culled, then tissue samples and oronasal swabs collected post-mortem for mycobacterial culture and Ultra testing, respectively. The Ultra detected MTBC DNA in 5/12 swabs from M. bovis culture-confirmed buffaloes. Oronasal swabs from M. bovis negative buffaloes (n = 20) were negative on Ultra, indicating the high specificity of this test. This study showed that MTM can successfully preserve MTBC DNA in oronasal swabs. The proportion of MTBC positive oronasal swabs was higher than expected and suggests that the Ultra may be an additional method for identifying infected buffaloes. Further studies are needed to confirm the utility of the Ultra assay with oronasal swabs as an assay to evaluate possible MTBC shedding in buffaloes.
Tidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung ...strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration.
Twenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined.
There were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups.
This open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted.
ACTRN12607000465459.
OBJECTIVES:To determine factors independently associated with readmission to ICU and the independent association of readmission with subsequent mortality.
DESIGN:Prospective multicenter observational ...study.
SETTING:Forty ICUs in Australia and New Zealand.
PATIENTS:Consecutive adult patients discharged alive from ICU to hospital wards between September 2009 and February 2010.
INTERVENTIONS:Measurement of hospital mortality.
MEASUREMENTS AND MAIN RESULTS:We studied 10,210 patients and 674 readmissions. The median age was 63 years (interquartile range, 49–74), and 6,224 (61%) were male. The majority of readmissions were unplanned (84.1%) but only deemed preventable in a minority (8.9%) of cases. Time to first readmission was shorter for unplanned than planned readmission (3.2 vs 6.9 d; p < 0.001). Primary diagnosis changed between admission and readmission in the majority of patients (60.2%) irrespective of planned (58.2%) or unplanned (60.6%) status. Using recurrent event analysis incorporating patient frailty, we found no association between readmissions and hospital survival (hazard ratiosfirst readmission 0.88, second readmission 0.90, third readmission 0.44; p > 0.05). In contrast, age (hazard ratio, 1.03), a medical diagnosis (hazard ratio, 1.43), inotrope use (hazard ratio, 3.47), and treatment limitation order (hazard ratio, 17.8) were all independently associated with outcome.
CONCLUSIONS:In this large prospective study, readmission to ICU was not an independent risk factor for mortality.
The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ...ophthalmoscopy (AOSLO).
Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO.
Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse.
Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology.
Mycobacterium bovis is the causative agent of bovine tuberculosis (bTB) in wildlife. Confirmation of M. bovis infection relies on mycobacterial culture, which is time-consuming. Collection and ...transportation of infectious material also pose a human health risk. PrimeStore Molecular Transport Medium (MTM) has been shown to effectively inactivate infectious organisms, making it a safe method for handling infectious samples. This study investigated an in-field sampling technique for rapid, safe detection of M. bovis in buffalo tissues. Potentially infected tissues from bTB test-positive buffaloes were swabbed at post-mortem examination and stored in PrimeStore MTM at ambient temperature until Xpert MTB/RIF Ultra testing was performed. Additionally, tissue samples were frozen and transported before homogenisation for culture and Ultra testing. Oral swabs were collected from M. bovis-unexposed buffaloes as a negative control cohort. Mycobacterium tuberculosis complex (MTBC) DNA was detected by Ultra in 13/16 tissue swabs and 9/16 matched tissue homogenates from culture-confirmed M. bovis-positive buffalo tissues. MTBC DNA was not detected in swabs from M. bovis-unexposed animals, showing the potentially high specificity of Ultra with PrimeStore swabs. PrimeStore MTM sample processing, in combination with the Ultra assay, has the potential to provide a safe, rapid post-mortem screening test for M. bovis in buffaloes.
The purpose of the study was to assess the long term outcome and quality of life of patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) for ...refractory hypoxemia.
A retrospective observational study with prospective health related quality of life (HRQoL) assessment was conducted in ARDS patients who had ECMO as a rescue therapy for reversible refractory hypoxemia from January 2009 until April 2011 in a tertiary Australian centre. Survival and long-term quality of life assessment, using the Short-Form 36 (SF-36) and the EuroQol health related quality of life questionnaire (EQ5D) were assessed and compared to international data from other research groups.
Twenty-one patients (mean age 36.3 years) with ARDS receiving ECMO for refractory hypoxemia were studied. Eighteen (86%) patients were retrieved from external intensive care units (ICUs) by a dedicated ECMO retrieval team. Eleven (55%) had H1N1 influenza A-associated pneumonitis. Eighteen (86%) patients survived to hospital discharge. Of the 18 survivors, ten (56%) were discharged to other hospitals and 8 (44%) were discharged directly home. Sequelae and health related quality of life were evaluated for 15 of the 18 (71%) long-term survivors (assessment at median 8 months). Mean SF-36 scores were significantly lower across all domains compared to age and sex matched Australian norms. Mean SF-36 scores were lower (minimum important difference at least 5 points) than previously described ARDS survivors in the domains of general health, mental health, vitality and social function. One patient had long-term disability as a result of ICU acquired weakness. Only 26% of survivors had returned to previous work levels at the time of follow-up.
This ARDS cohort had a high survival rate (86%) after use of ECMO support for reversible refractory hypoxemia. Long term survivors had similar physical health but decreased mental health, general health, vitality and social function compared to other ARDS survivors and an unexpectedly poor return to work.
Comparisons between institutions of intensive care unit (ICU) length of stay (LOS) are significantly confounded by individual patient characteristics, and currently there is a paucity of methods ...available to calculate risk-adjusted metrics.
We extracted de-identified data from the Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database for admissions between January 1 2011 and December 31 2015. We used a mixed-effects log-normal regression model to predict LOS using patient and admission characteristics. We calculated a risk-adjusted LOS ratio (RALOSR) by dividing the geometric mean observed LOS by the exponent of the expected Ln-LOS for each site and year. The RALOSR is scaled such that values <1 indicate a LOS shorter than expected, while values >1 indicate a LOS longer than expected. Secondary mixed effects regression modelling was used to assess the stability of the estimate in units over time.
During the study there were a total of 662,525 admissions to 168 units (median annual admissions = 767, IQR:426-1121). The mean observed LOS was 3.21 days (median = 1.79 IQR = 0.92-3.52) over the entire period, and declined on average 1.97 hours per year (95%CI:1.76-2.18) from 2011 to 2015. The RALOSR varied considerably between units, ranging from 0.35 to 2.34 indicating large differences after accounting for case-mix.
There are large disparities in risk-adjusted LOS among Australian and New Zealand ICUs which may reflect differences in resource utilization.
Previous studies suggested an association between after-hours intensive care unit (ICU) discharge and increased hospital mortality. Their retrospective design and lack of correction for patient ...factors present at the time of discharge make this association problematic.
To determine factors independently associated with mortality after ICU discharge.
This was a prospective, multicenter, binational observational study involving 40 ICUs in Australia and New Zealand. Participants were consecutive adult patients discharged alive from the ICU between September 2009 and February 2010.
We studied 10,211 patients discharged alive from the ICU. Median age was 63 years (interquartile range, 49-74), 6,224 (61%) were male, 5,707 (56%) required mechanical ventilation, and their median Acute Physiology and Chronic Health Evaluation III risk of death was 9% (interquartile range, 3-25%). A total of 8,539 (83.6%) patients were discharged in-hours (06:00-18:00) and 1,672 (16.4%) after-hours (18:00-06:00). Of these, 408 (4.8%) and 124 (7.4%), respectively, subsequently died in hospital (P < 0.001). After risk adjustment for markers of illness severity at time of ICU discharge including limitations of medical therapy (LOMT) orders, the time of discharge was no longer a significant predictor of mortality. The presence of a LOMT order was the strongest predictor of death (odds ratio, 35.4; 95% confidence interval, 27.5-45.6).
In this large, prospective, multicenter, binational observational study, we found that patient status at ICU discharge, particularly the presence of LOMT orders, was the chief predictor of hospital survival. In contrast to previous studies, the timing of discharge did not have an independent association with mortality.
Trait reward sensitivity, risk for developing substance use, and mood disorders have each been linked with altered striatal responses to reward. Moreover, striatal response to reward is sensitive to ...social context, such as the presence of a peer, and drugs are often sought out and consumed in social contexts or as a result of social experiences. Thus, mood disorder symptoms, striatal responses to social context and social reward may play a role in substance use. To investigate this possibility, this dataset was collected as part of a National Institute on Drug Abuse (NIDA) grant titled “Aberrant Reward Sensitivity: Mechanisms Underlying Substance Use” (R03-DA046733). The overarching goal was to characterize the associations between neural responses to social and nonsocial rewards, trait reward sensitivity, substance use, and mood disorder symptoms. After obtaining questionnaire data quantifying reward sensitivity, substance use, and other psychosocial characteristics, young adults (N=59; 14 male, 45 female; mean age: 20.89 years ± 1.75 years) completed four fMRI tasks testing different features of social and reward processing. These included: 1) a strategic reward-based decision-making task with Ultimatum and Dictator Game conditions; 2) a task where participants shared rewards or losses with peers, strangers, or non-human partners; 3) a task in which participants received well-matched social and monetary rewards and punishment; and 4) a monetary incentive delay (MID) task in which participants tried to obtain or avoid rewards and losses of different magnitude. This dataset includes sociodemographic questionnaire data, anatomical, task-based fMRI, and corresponding behavioral task-based data. We outline several opportunities for extension and reuse, including exploration of individual differences, cross-task comparisons, and representational similarity analyses.
The non-Newtonian flow of dilute aqueous polyethylene oxide (PEO) solutions through micro-fabricated planar abrupt contraction–expansions is investigated. The small lengthscales and high deformation ...rates in the contraction throat lead to significant extensional flow effects even with dilute polymer solutions having time constants on the order of milliseconds. By considering the definition of the elasticity number,
El
=
Wi/
Re, we show that the lengthscale of the geometry is key to the generation of strong viscoelastic effects, such that the same flow behaviour cannot be reproduced using the equivalent macro-scale geometry using the same fluid. We observe significant vortex growth upstream of the contraction plane, which is accompanied by an increase of more than 200% in the dimensionless extra pressure drop across the contraction. Streak photography and video-microscopy using epifluorescent particles shows that the flow ultimately becomes unstable and three-dimensional. The moderate Reynolds numbers (0.44
≤
Re
≤
64) associated with these high Weissenberg number (0
≤
Wi
≤
548) micro-fluidic flows results in the exploration of new regions of the
Re–
Wi parameter space in which the effects of both elasticity and inertia can be observed. Understanding such interactions will be increasingly important in micro-fluidic applications involving complex fluids and can best be interpreted in terms of the elasticity number,
El
=
Wi/
Re, which is independent of the flow kinematics and depends only on the fluid rheology and the characteristic size of the device.
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