Primary care usage at the end of life: a retrospective cohort study of cancer patients using linked primary and hospital care data.

PURPOSE: Health service use is most intensive in the final year of a person's life, with 80% of this expenditure occurring in hospital. Close involvement of primary care services has been promoted to enhance quality end-of-life care that is appropriate to the needs of patients. However, the relationship between primary care involvement and patients' use of hospital care is not well described. This study aims to examine primary care use in the last year of life for cancer patients and its relationship to hospital usage. METHODS: Retrospective cohort study in Victoria, Australia, using linked routine care data from primary care, hospital and death certificates. Patients were included who died related to cancer between 2008 and 2017. RESULTS: A total of 758 patients were included, of whom 88% (n = 667) visited primary care during the last 6 months (median 9.1 consultations). In the last month of life, 45% of patients were prescribed opioids, and 3% had imaging requested. Patients who received home visits (13%) or anticipatory medications (15%) had less than half the median bed days in the last 3 months (4 vs 9 days, p < 0.001, 5 vs 10 days, p = 0.001) and 1 month of life (0 vs 2 days, p = 0.002, 0 vs 3 days, p < 0.001), and reduced emergency department presentations (32% vs 46%, p = 0.006, 31% vs 47% p < 0.001) in the final month. CONCLUSION: This study identifies two important primary care processes-home visits and anticipatory medication-associated with reduced hospital usage and intervention at the end of life.

Greywater treatment in a green wall using different filter materials and hydraulic loading rates.

Green walls in urban environments can be both an aesthetic feature and be of practical use in greywater treatment. This study evaluates the effect of different loading rates (4.5 l/d, 9 l/d, and 18 l/d) on the efficiency of treating actual greywater from a city district in a pilot-scale green wall with five different filter materials as substrates (biochar, pumice, hemp fiber, spent coffee grounds (SCG), and composted fiber soil (CFS)). Three cool climate plant species, Carex nigra, Juncus compressus, and Myosotis scorpioides, were chosen for the green wall. The following parameters were evaluated: biological oxygen demand (BOD), fractions of organic carbon, nutrients, indicator bacteria, surfactants, and salt. Three of the five materials investigated - biochar, pumice, and CFS - showed promising treatment efficiencies. The respective overall reduction efficiencies of BOD, total nitrogen (TN) and total phosphorus (TP) were 99%, 75%, and 57% for biochar; 96%, 58%, and 61% for pumice; and 99%, 82% and 85% for CFS. BOD was stable in the biochar filter material with effluent concentrations of 2 mg/l across all investigated loading rates. However, higher loading rates had a significantly negative effect on hemp and pumice for BOD. Interestingly, the highest loading rate (18 l/d) flowing over pumice removed the highest levels of TN (80%) and TP (86%). Biochar was the most effective material in removing indicator bacteria, with a 2.2-4.0 Log10 reduction for E. coli and enterococci. SCG was the least efficient material, giving a higher BOD in the effluent than in the influent. Therefore, this study presents the potential of natural and waste-derived filter materials to treat greywater effectively and the results can contribute to the future development of nature-based greywater treatment and management practices in urban areas.

Plants against pathogens: Effect of significant antimicrobial-producing plants on faecal microbe inactivation throughout the soil profile of stormwater biofilters.

Stormwater biofilters have demonstrated promising yet variable removal of faecal microorganisms. Significant antimicrobial-producing plants have been proposed as an inexpensive, safe and easily adaptable component of biofilter design to enhance faecal pathogen treatment. The aim of the present study was to investigate whether significant antimicrobial-producing plants improved faecal bacterial inactivation throughout the biofilter soil profile, focusing on four key treatment zones. These were specifically the top sediment/surface layer; the rhizosphere (soil directly attached to and influenced by plant roots); bulk soil (soil not directly associated with roots); and the submerged/saturated zone. Biofilters were configured with either: (1) no plant; (2) Carex appressa, the most highly recommended plant species in Australian biofilter adoption guidelines; or (3) one of two significant antimicrobial-producing Australian plant species, Melaleuca linariifolia or Melaleuca fulgens (n = 3 each). Following 16 months' maturation, systems were dosed with semi-synthetic stormwater containing faecal bacteria Escherichia coli and Enterococcus faecalis to monitor their ensuing die-off within all major biofilter treatment zones. Bacterial inactivation was generally more rapid in M. fulgens and M. linariifolia than C. appressa biofilters, with E. faecalis demonstrating an overall enhanced resistance to inactivation. Top sediment tended to exhibit the highest inactivation rates, significantly correlated with sunlight exposure. Conversely, the rhizosphere supported comparatively prolonged faecal bacterial survival. The authors recommend further investigation of melaleucas and similar highly antimicrobial-producing plants for enhanced faecal pathogen treatment within biofilters and related treatment contexts.

Sustainable micropollutant bioremediation via stormwater biofiltration system.

Waters contaminated with micropollutants are of environmental and public health concern globally. Stormwater is a significant source of anthropogenic micropollutants to receiving waters. Hence, sustainable stormwater remediation is needed to reduce contamination of waterways. Yet designing sustainable bioremediation solutions, including those targeted to remove micropollutants, is a major scientific challenge. This study aimed to adapt the design of stormwater biofiltration systems, to improve the removal of micropollutants and understand the role of the micropollutant-degrading bacteria in this bioremediation process. We investigated the atrazine removal performance of a prototype biofiltration system, in which the filter media was supplemented with Granulated Activated Carbon (GAC). The prototype biofiltration system completely removed atrazine to below detectable limits, significantly exceeding the GAC's adsorption capacity alone, suggesting other biological processes were present. We showed that atrazine degradation capacity, measured by the kinetics of the trzN gene abundance, was accelerated in the prototype system compared to the standard system (which had no added GAC; 0.8 vs. 0.37 week-1, respectively). Notably, this high level of atrazine removal did not come at the expense of the removal performance of other typical stormwater macropollutants (e.g., nutrients, suspended solids). The prototype biofiltration system showed a proof-of-concept of sustaining microbial remediation of a model micropollutant alongside stormwater macropollutants, which could be used to reduce impacts on receiving waterways and protect our ecosystems and human health.

Calibration and sensitivity analysis of a novel water flow and pollution model for future city planning: Future Urban Stormwater Simulation (FUSS).

Planning for future urban development and water infrastructure is uncertain due to changing human activities and climate. To quantify these changes, we need adaptable and fast models that can reliably explore scenarios without requiring extensive data and inputs. While such models have been recently considered for urban development, they are lacking for stormwater pollution assessment. This work proposes a novel Future Urban Stormwater Simulation (FUSS) model, utilizing a previously developed urban planning algorithm (UrbanBEATS) to dynamically assess pollution changes in urban catchments. By using minimal input data and adding stochastic point-source pollution to the build-up/wash-off approach, this study highlights calibration and sensitivity analysis of flow and pollution modules, across the range of common stormwater pollutants. The results highlight excellent fit to measured values in a continuous rainfall simulation for the flow model, with one significant calibration parameter. The pollution model was more variable, with TSS, TP and Pb showing high model efficiency, while TN was predicted well only across event-based assessment. The work further explores the framework for the model application in future pollution assessment, and points to the future work aiming to developing land-use dependent model parameter sets, to achieve flexibility for model application across varied urban catchments.

Illicit discharge detection in stormwater drains using an Arduino-based low-cost sensor network.

Illicit discharges in urban stormwater drains are a major environmental concern that deteriorate downstream waterway health. Conventional detection methods such as stormwater drain visual inspection and dye testing have fundamental drawbacks and limitations which can prevent easy location and elimination of illegal discharges in a catchment. We deployed 22 novel low-cost level, temperature and conductivity sensors across an urban catchment in Melbourne for a year to monitor the distributed drainage network, thereby detecting likely illicit discharges ranging from a transitory flow with less than 10 minutes to persistent flows lasting longer than 20 hours. We discuss rapid deployment methods, real-time data collection and online processing. The ensemble analysis of all dry weather flow data across all sites indicates that: (i) large uncertainties are associated with discharge frequency, duration, and variation in water quality within industrial and residential land uses; (ii) most dry weather discharges are intermittent and transient flows which are difficult to detect and not simply due to cross-connections with the sewerage network; (iii) detectable diurnal discharge patterns can support mitigation efforts, including policies and regulatory measures (e.g., enforcement or education) to protect receiving waterways; and, (iv) that it is possible to cost effectively isolate sources of dry weather pollution using a distributed sensor network.

Sex differences in the physiological responses to exercise-induced dehydration: consequences and mechanisms.

Physiological strain during exercise is increased by mild dehydration (∼1%-3% body mass loss). This response may be sex-dependent, but there are no direct comparative data in this regard. This review aimed to develop a framework for future research by exploring the potential impact of sex on thermoregulatory and cardiac strain associated with exercise-induced dehydration. Sex-based comparisons were achieved by comparing trends from studies that implemented similar experimental protocols but recruited males and females separately. This revealed a higher core temperature (Tc) in response to exercise-induced dehydration in both sexes; however, it seemingly occurred at a lower percent body mass loss in females. Although less clear, similar trends existed for cardiac strain. The average female may have a lower body water volume per body mass compared with males, and therefore the same percent body mass loss between the sexes may represent a larger portion of total body water in females potentially posing a greater physiological strain. In addition, the rate at which Tc increases at exercise onset might be faster in females and induce a greater thermoregulatory challenge earlier into exercise. The Tc response at exercise onset is associated with lower sweating rates in females, which is commonly attributed to sex differences in metabolic heat production. However, a reduced sweat gland sensitivity to stimuli, lower fluid output per sweat gland, and sex hormones promoting fluid retention in females may also contribute. In conclusion, the limited evidence suggests that sex-based differences exist in thermoregulatory and cardiac strain associated with exercise-induced dehydration, and this warrants future investigations.

High prevalence of vertebral fractures in seizure patients with normal bone density receiving chronic anti-epileptic drugs.

People with epilepsy who take certain medications are at risk for developing osteoporosis and fractures of the vertebrae that commonly go undiagnosed. By using technology available in a bone density scan, we observed at least one fracture in many subjects with bone density in the normal and osteopenic range. PURPOSE/INTRODUCTION: Chronic use of antiepileptic drugs (AEDs), both enzyme-inducing (phenytoin, phenobarbital, carbamazepine, and primidone) and non-enzyme-inducing (i.e., valproate), is recognized as a cause of secondary osteoporosis. Vertebral compression fractures (VF) are the most common type of osteoporotic fractures and may confer an increased risk of future hip, wrist, and vertebral fractures. Vertebral compression fractures in the general population are frequently asymptomatic, and under-diagnosed. The purpose of this study is to describe the prevalence of VF in a cohort of male veterans with epilepsy on chronic AEDs. METHODS: The cohort for this study consisted of 146 male veterans who carried a diagnosis of epilepsy and were chronic users of AEDs known to cause osteoporosis (phenobarbital, phenytoin, carbamazepine, primidone, and valproate). Chronic AED use was defined as receiving an AED for at least 2 years. Subjects were previously seen in the osteoporosis clinic and had been evaluated by a dual-energy X-Ray absormetry (DXA) instrument including morphometric studies following a standard vertebral fracture assessment (VFA) protocol during the same DXA imaging acquisition session. RESULTS: The mean age was 63 years. Low bone mineral density defined as osteoporosis or osteopenia was observed in 29% and 43% respectively. We observed at least one VF in 41 % of the subjects who had normal BMD, 54% in the osteopenic range, and 75% in the osteoporotic range. CONCLUSIONS: By performing a VFA in addition to standard bone densitometric studies, we disclosed a large prevalence of compression fractures in individuals with epilepsy chronically treated with AEDs who had BMDs in the normal and osteopenic ranges. The addition of VFA or other imaging methods to evaluate VF should be included in the evaluation of bone health in individuals with epilepsy receiving AEDs since it may modify treatment recommendations to prevent future osteoporotic fractures.

Rise of the killer plants: investigating the antimicrobial activity of Australian plants to enhance biofilter-mediated pathogen removal.

BACKGROUND: Biofilters are soil-plant based passive stormwater treatment systems which demonstrate promising, although inconsistent, removal of faecal microorganisms. Antimicrobial-producing plants represent a safe, inexpensive yet under-researched biofilter design component that may enhance treatment reliability. The mechanisms underlying plant-mediated microbial removal in biofilters have not been fully elucidated, particularly with respect to antimicrobial production. The aim of this study was therefore to inform biofilter vegetation selection guidelines for optimal pathogen treatment by conducting antimicrobial screening of biofilter-suitable plant species. This involved: (1) selecting native plants suitable for biofilters (17 species) in a Victorian context (southeast Australia); and (2) conducting antimicrobial susceptibility testing of selected plant methanolic extracts (≥ 5 biological replicates/species; 86 total) against reference stormwater faecal bacteria (Salmonella enterica subsp. enterica ser. Typhimurium, Enterococcus faecalis and Escherichia coli). RESULTS: The present study represents the first report on the inhibitory activity of polar alcoholic extracts from multiple tested species. Extracts of plants in the Myrtaceae family, reputed for their production of antimicrobial oils, demonstrated significantly lower minimum inhibitory concentrations (MICs) than non-myrtaceous candidates (p < 0.0001). Melaleuca fulgens (median MIC: 8 mg/mL; range: [4-16 mg/mL]), Callistemon viminalis (16 mg/mL, [2-16 mg/mL]) and Leptospermum lanigerum (8 mg/mL, [4-16 mg/mL]) exhibited the strongest inhibitory activity against the selected bacteria (p < 0.05 compared to each tested non-myrtaceous candidate). In contrast, the Australian biofilter gold standard Carex appressa demonstrated eight-fold lower activity than the highest performer M. fulgens (64 mg/mL, [32-64 mg/mL]). CONCLUSION: Our results suggest that myrtaceous plants, particularly M. fulgens, may be more effective than the current vegetation gold standard in mediating antibiosis and thus improving pathogen treatment within biofilters. Further investigation of these plants in biofilter contexts is recommended to refine biofilter vegetation selection guidelines.

New prebiotic chemistry inspired filter media for stormwater/greywater disinfection.

Greywater and stormwater have received significant attention due to increasing water scarcity. Passive filtration such as biofiltration has been a popular treatment method with its low energy input and environmental friendliness. However, pathogen removal capacity needs improvement to achieve safe water quality. In this study, a prebiotic chemistry inspired copolymer based on aminomalononitrile and 3,4,5-trihydroxybenzaldehyde (AMNT30) was introduced to develop antimicrobial media for passive filtration. The AMNT30 polymer provided an adhesive coating on zeolite substrates following a spontaneous polymerisation process at room temperature. AMNT30 coated media were investigated for metal loading capacity, surface morphology, E. coli removal and metal leaching after filtration of different water sources (i.e. stormwater, greywater, and deionised water) at low/high conductivity. The coating enhanced metal ion loading on the surface and demonstrated that >8 log reduction of E. coli can be achieved for silver loaded materials compared to a 1 log reduction for copper loaded materials. The coating also increased the stability of the metals on the media irrespective of inflow characteristics. This study provided the first example using AMNT30 to create antimicrobial water purification media. It is expected that this technology will find applications in the water treatment industry.

Investigation of the HotDog patient warming system: detection of thermal gradients.

OBJECTIVE: To assess the performance of an active patient-warming device. MATERIALS AND METHODS: Temperatures of an active patient-warming device (HotDog system) were measured at various time points using an infrared thermometer. The study was conducted in two phases: Phase 1 compared temperatures among four different areas of the warming blanket. Phase 2 compared conditions simulating different scenarios using a weighted patient simulator. RESULTS: Phase 1: Three out of four positions on the warming blanket had significantly different temperature measurements. Phase 2: Temperature output by the warming blanket was reduced: (1) in the absence of the patient simulator placed across the blanket (-1·9°C, P=0·013); (2) if the patient simulator was placed away from the blanket sensor (-2·0°C, P=0·009); and (3) if there was fluid between the patient simulator and warming blanket (-2·2°C, P=0·004). In a majority of measurements (95%), the set temperature of 43°C on the control unit was not reached (range, 29·8 to 42·9°C) and 2·3% of measurements were higher (range, 43·1 to 45·8°C) than the control unit set temperature of 43°C. CLINICAL SIGNIFICANCE: Measured temperatures on the active warming blanket did not reflect control unit settings. This could result in the potential for hyperthermic injury, ineffectual heating and uneven heat distribution.

NOX1 loss-of-function genetic variants in patients with inflammatory bowel disease.

Genetic defects that affect intestinal epithelial barrier function can present with very early-onset inflammatory bowel disease (VEOIBD). Using whole-genome sequencing, a novel hemizygous defect in NOX1 encoding NAPDH oxidase 1 was identified in a patient with ulcerative colitis-like VEOIBD. Exome screening of 1,878 pediatric patients identified further seven male inflammatory bowel disease (IBD) patients with rare NOX1 mutations. Loss-of-function was validated in p.N122H and p.T497A, and to a lesser degree in p.Y470H, p.R287Q, p.I67M, p.Q293R as well as the previously described p.P330S, and the common NOX1 SNP p.D360N (rs34688635) variant. The missense mutation p.N122H abrogated reactive oxygen species (ROS) production in cell lines, ex vivo colonic explants, and patient-derived colonic organoid cultures. Within colonic crypts, NOX1 constitutively generates a high level of ROS in the crypt lumen. Analysis of 9,513 controls and 11,140 IBD patients of non-Jewish European ancestry did not reveal an association between p.D360N and IBD. Our data suggest that loss-of-function variants in NOX1 do not cause a Mendelian disorder of high penetrance but are a context-specific modifier. Our results implicate that variants in NOX1 change brush border ROS within colonic crypts at the interface between the epithelium and luminal microbes.

Modelling transitions in urban water systems.

Long term planning of urban water infrastructure requires acknowledgement that transitions in the water system are driven by changes in the urban environment, as well as societal dynamics. Inherent to the complexity of these underlying processes is that the dynamics of a system's evolution cannot be explained by linear cause-effect relationships and cannot be predicted under narrow sets of assumptions. Planning therefore needs to consider the functional behaviour and performance of integrated flexible infrastructure systems under a wide range of future conditions. This paper presents the first step towards a new generation of integrated planning tools that take such an exploratory planning approach. The spatially explicit model, denoted DAnCE4Water, integrates urban development patterns, water infrastructure changes and the dynamics of socio-institutional changes. While the individual components of the DAnCE4Water model (i.e. modules for simulation of urban development, societal dynamics and evolution/performance of water infrastructure) have been developed elsewhere, this paper presents their integration into a single model. We explain the modelling framework of DAnCE4Water, its potential utility and its software implementation. The integrated model is validated for the case study of an urban catchment located in Melbourne, Australia.

Avoiding "Rash" Conclusions: Challenge of IgA Vasculitis in Adults.

IgA vasculitis is primarily a pediatric disease that is rarely encountered in adults. With adults, gastrointestinal manifestations are quite common, yet are nonspecific and may overlap with other diseases, particularly Crohn's disease, which can make the diagnosis a challenging task. Treatment is controversial given the disease course is usually self-limited with few serious complications. We present a case of IgA vasculitis in an adult patient with limited extraintestinal findings illustrating the complexity of arriving at the correct diagnosis.

Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery.

One of the greatest challenges for the development of genetic therapies is the efficient targeted delivery of therapeutic nucleic acids. Towards this goal, we have introduced a new engineering initiative in self-assembly of biologically safe and stable nanovesicle complexes (∼90 to 140nm) derived from giant unilamellar vesicle (GUV) precursors and comprising plasmid DNA or siRNA and targeting peptide ligands. The biological performance of the engineered nanovesicle complexes were studied both in vitro and in vivo and compared with cationic liposome-based lipopolyplexes. Compared with cationic lipopolyplexes, nanovesicle complexes did not show advantages in transfection and cell uptake. However, nanovesicle complexes neither displayed significant cytotoxicity nor activated the complement system, which are advantageous for intravenous injection and tumour therapy. On intravenous administration into a neuroblastoma xenograft mouse model, nanovesicle complexes were found to distribute throughout the tumour interstitium, thus providing an alternative safer approach for future development of tumour-specific therapeutic nucleic acid interventions. On oropharyngeal instillation, nanovesicle complexes displayed better transfection efficiency than cationic lipopolyplexes. The technological advantages of nanovesicle complexes, originating from GUVs, over traditional cationic liposome-based lipopolyplexes are discussed. STATEMENT OF SIGNIFICANCE: The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of safe, non-viral vectors to deliver therapeutic cargos in a variety of disorders.

Source tracking using microbial community fingerprints: Method comparison with hydrodynamic modelling.

Urban estuaries around the world are experiencing contamination from diffuse and point sources, which increases risks to public health. To mitigate and manage risks posed by elevated levels of contamination in urban waterways, it is critical to identify the primary water sources of contamination within catchments. Source tracking using microbial community fingerprints is one tool that can be used to identify sources. However, results derived from this approach have not yet been evaluated using independent datasets. As such, the key objectives of this investigation were: (1) to identify the major sources of water responsible for bacterial loadings within an urban estuary using microbial source tracking (MST) using microbial communities; and (2) to evaluate this method using a 3-dimensional hydrodynamic model. The Yarra River estuary, which flows through the city of Melbourne in South-East Australia was the focus of this study. We found that the water sources contributing to the bacterial community in the Yarra River estuary varied temporally depending on the estuary's hydrodynamic conditions. The water source apportionment determined using microbial community MST correlated to those determined using a 3-dimensional hydrodynamic model of the transport and mixing of a tracer in the estuary. While there were some discrepancies between the two methods, this investigation demonstrated that MST using bacterial community fingerprints can identify the primary water sources of microorganisms in an estuarine environment. As such, with further optimization and improvements, microbial community MST has the potential to become a powerful tool that could be practically applied in the mitigation of contaminated aquatic systems.