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This study investigated cases diagnosed as allergic contact dermatitis (ACD) in emergency departments (EDs) and management.A multisite retrospective study of patients attending EDs in metropolitan Melbourne between July 2017 and June 2018 was performed. Using International Statistical Classification of Disease-10 (ICD-10) codes, the Victorian Agency for Health Information generated a list of cases of contact dermatitis (CD). Demographic and clinical data were analysed.Two hundred twenty-eighty patients from 14 different sites were diagnosed with ACD. Hair dyes caused the most cases, and one such case was admitted to hospital. It was apparent from the specified causes that cases of irritant CD were misdiagnosed as ACD. There were significant differences in management with dermatology input, with dermatologists more often advising oral corticosteroids (33.3% vs. 14.5%, P = 0.004) topical corticosteroids (92.9% vs. 38.7%, P 0.01), emollients (38.1% vs. 20.4%, P = 0.01) and less often advising antihistamines (16.7% vs. 44.6%, P 0.001). With dermatology input, potent or very potent steroids were more likely to be prescribed (69.3% vs. 11.1%, P 0.001); without, a mild potency steroid was more likely to be prescribed (63.9% vs. 4%, P = 0.01).Improved understanding, diagnosis and management of CD are needed in EDs.

AIM Pre-emptive kidney transplantation (PKT) is generally considered the optimal treatment for kidney failure as it minimises dialysis-associated morbidity and mortality and is associated with improved allograft survival. This study aimed to determine rates of paediatric PKT in New Zealand, identify barriers to PKT and consider potential interventions to influence future rates of pre-emptive transplantation. METHODS Children commencing kidney replacement therapy between 2005 and 2017 in New Zealand were included. Descriptive analysis considered those referred late (referral

A four-month-old male Springer Spaniel presented for investigation of ascites of three weeks’ duration. On transthoracic echocardiogram, cor triatriatum dexter was diagnosed with associated right-sided congestive heart failure. Medical therapy consisting of furosemide, spironolactone and benazepril was initiated. On the day of surgery, the dog was premedicated with methadone 0.2 mg/kg intravenously, and general anaesthesia was induced with midazolam 0.2 mg/kg intravenously and propofol 25 mg. Anaesthesia was maintained with isoflurane in oxygen. Concurrently, constant rate infusions of fentanyl 0.2–0.3 µg/kg/minute and lidocaine 50 µg/kg/minute were administered. Ventricular premature complexes and ventricular tachycardia developed during the placement of the catheter and during the first balloon dilation. Antiarrhythmic therapy with lidocaine 2 mg/kg was required. At the end of the procedure, acepromazine 5 µg/kg intravenous and buprenorphine 20 µg/kg intravenous were administered. Recovery from general anaesthesia was uneventful.

Rational, aims, and objectives The Family Nurse Partnership (FNP) is a licensed intensive home visiting intervention developed in the United States. It has been provided in England by the Department of Health since 2006. The Building Blocks trial assessed the effectiveness and cost-effectiveness of FNP in England. Methods We performed a cost-utility analysis (National Health Service (NHS) perspective) alongside the Building Blocks trial (over 2.5 y). The analysis was conducted in accordance with National Institute for Health and Clinical Excellence (NICE) reference case standards. Health-related quality of life was elicited from mothers using the EQ-5D-3L. Resource-use data were collected from self-reported questionnaires, Hospital Episode Statistics, general practitioner records and the central Department of Health FNP database. Costs and quality-adjusted life years (QALYs) were discounted at 3.5%. The base case analysis used an intention to treat approach on the imputed dataset using multiple imputation. Results The FNP intervention costs on average £1812 more per participant compared to usual care (95% confidence interval: −£2700; £5744). Incremental adjusted mean QALYs are marginally higher for FNP (mean difference 0.0036, 95% confidence interval: −0.017; 0.025). The probability of FNP being cost-effective is less than 20% given the current NICE willingness to pay threshold of £20 000 per additional QALY. The results were robust to sensitivity analyses. Conclusion Given the absence of significant benefits of FNP in terms of the primary outcomes of the trial and only marginal maternal QALY gains, FNP does not represent a cost-effective intervention when compared with existing services already offered to young pregnant women.

Objective We review the published cases of clozapine-induced myocarditis and describe reasons for the higher incidence in Australia (>1%) than elsewhere (

Rationale, aims and objectives Randomized controlled trials (RCTs) are widely used in health care research to provide high-quality evidence of effectiveness of an intervention. However, sometimes a study does not require an RCT in order to answer its primary objective; a case-finding design may be more appropriate. The aim of this paper was to introduce a new study design that nests a waiting list RCT within a case-finding study. Methods An example of the new study design is the DOC Study, which primarily aims to determine the diagnostic accuracy of lung function tests for chronic obstructive pulmonary disease. It also investigates the impact of lung function tests on smoking behaviour through use of a waiting list design. The first step of the study design is to obtain participants’ consent. Individuals are then randomized to one of two groups; either the ‘intervention now’group or the ‘intervention later’group, that is, participants are placed on a waiting list. All participants receive the same intervention; the only difference between the groups is the timing of the intervention. Results and conclusions The design addresses patient preference issues and recruitment issues that can arise in other trial designs. Potential limitations include differential attrition between study groups and potential demoralization for the ‘intervention later’ group. The ‘waiting list case-finding trial’design is a valuable method that could be applied to case-finding studies; the design enables the case-finding component of a study to be maintained while simultaneously exploring additional hypotheses through conducting a trial.

Purpose: To determine the potential of spectral computed tomography (CT) with Medipix3 for quantifying fat, calcium, and iron in soft tissues within small animal models and surgical specimens of diseases such as fatty liver (metabolic syndrome) and unstable atherosclerosis. Methods: The spectroscopic method was applied to tomographic data acquired using a micro-CT system incorporating a Medipix3 detector array with silicon sensor layer and microfocus x-ray tube operating at 50 kVp. A 10 mm diameter perspex phantom containing a fat surrogate (sunflower oil) and aqueous solutions of ferric nitrate, calcium chloride, and iodine was imaged with multiple energy bins. The authors used the spectroscopic characteristics of the CT number to establish a basis for the decomposition of soft tissue components. The potential of the method of constrained least squares for quantifying different sets of materials was evaluated in terms of information entropy and degrees of freedom, with and without the use of a volume conservation constraint. The measurement performance was evaluated quantitatively using atheroma and mouse equivalent phantoms. Finally the decomposition method was assessed qualitatively using a euthanized mouse and an excised human atherosclerotic plaque. Results: Spectral CT measurements of a phantom containing tissue surrogates confirmed the ability to distinguish these materials by the spectroscopic characteristics of their CT number. The assessment of performance potential in terms of information entropy and degrees of freedom indicated that certain sets of up to three materials could be decomposed by the method of constrained least squares. However, there was insufficient information within the data set to distinguish calcium from iron within soft tissues. The quantification of calcium concentration and fat mass fraction within atheroma and mouse equivalent phantoms by spectral CT correlated well with the nominal values (R 2 = 0.990 and R 2 = 0.985, respectively). In the euthanized mouse and excised human atherosclerotic plaque, regions of calcium and fat were appropriately decomposed according to their spectroscopic characteristics. Conclusions: Spectral CT, using the Medipix3 detector and silicon sensor layer, can quantify certain sets of up to three materials using the proposed method of constrained least squares. The system has some ability to independently distinguish calcium, fat, and water, and these have been quantified within phantom equivalents of fatty liver and atheroma. In this configuration, spectral CT cannot distinguish iron from calcium within soft tissues.

Aim Care services for older people are provided with the expectation of supporting carers in their caregiving role. The aim of the study is to investigate the association between the utilisation of care services by older people and the caregiving experience. Methods Cross-sectional design, involving a cohort of family carers (n = 119) of frail older people (≥70 years) enrolled in a clinical trial of frailty treatment in metropolitan Sydney from 2008 to 2011. The caregiving experience was measured in five domains: health, daily schedule, finance, family support and self-esteem (Caregiver Reaction Assessment tool). Results Multivariate regression analysis demonstrated an association between the utilisation of residential respite care and financial strain (β = −0.613, P = 0.049), after controlling for functional ability, co-residence and age. Conclusion There is a need to consider carers' financial barriers and concerns in regards to the utilisation of respite care services.

Aims and objectives. Identify and compare spiritual caring practice by palliative care and acute care registered nurses (RNs), determine any correlation between nurses’ spiritual perspective and their spiritual caring, and to investigate perceived barriers to spiritual caring. Background. Over the past decade there has been growing interest in spiritual caring in nursing. Professional nursing bodies have proposed spirituality and spiritual caring as an integral component of holistic nursing. Design. Cross sectional study. Methods. Palliative care RNs (n = 42) from one community palliative care service and three hospices, and acute care RNs (n = 50) from three major acute care hospitals all in metropolitan Sydney, Australia completed a research questionnaire. Two validated tools and a demographic survey were used to collect data. These tools measured spiritual perspectives including saliency of personal spirituality, spiritual views and engagement in spiritually-related activities; and spiritual practice including assessment, interventions and barriers to spiritual caring. Data were collected over a six-month period and interpreted with both descriptive and analytical statistics. Results. Significant differences were seen between the two RN groups. Palliative care RNs’ spiritual caring practice was more advanced and their spiritual perspective stronger; this relationship was positive. Both RN groups identified ‘insufficient time’ as the most common barrier to spiritual caring practice; ‘patient privacy’ was also common for acute care RNs. Conclusions. Palliative care RNs’ spiritual perspectives influenced their spiritual caring. These nurses were older and more career-advanced than the acute care RNs, which may explain the differences observed. Acute care RNs may benefit from additional support for their spiritual caring and to address perceived barriers. Relevance to clinical practice. The development of nurses’ spiritual perspective early in their preparation for practice, and the articulation and documentation of spiritual caring may enhance their spiritual caring practice. Further research on barriers to spiritual caring in acute care nursing environments is recommended.

P-glycoprotein (ABCB1/MDR1, EC 3.6.3.44), the major efflux transporter at the blood-brain barrier (BBB), is a formidable obstacle to CNS pharmacotherapy. Understanding the mechanism(s) for increased P-glycoprotein activity at the BBB during peripheral inflammatory pain is critical in the development of novel strategies to overcome the significant decreases in CNS analgesic drug delivery. In this study, we employed the λ-carrageenan pain model (using female Sprague-Dawley rats), combined with confocal microscopy and subcellular fractionation of cerebral microvessels, to determine if increased P-glycoprotein function, following the onset of peripheral inflammatory pain, is associated with a change in P-glycoprotein trafficking which leads to pain-induced effects on analgesic drug delivery. Injection of λ-carrageenan into the rat hind paw induced a localized, inflammatory pain (hyperalgesia) and simultaneously, at the BBB, a rapid change in colocalization of P-glycoprotein with caveolin-1, a key scaffolding/trafficking protein. Subcellular fractionation of isolated cerebral microvessels revealed that the bulk of P-glycoprotein constitutively traffics to membrane domains containing high molecular weight, disulfide-bonded P-glycoprotein-containing structures that cofractionate with membrane domains enriched with monomeric and high molecular weight, disulfide-bonded, caveolin-1-containing structures. Peripheral inflammatory pain promoted a dynamic redistribution between membrane domains of P-glycoprotein and caveolin-1. Disassembly of high molecular weight P-glycoprotein-containing structures within microvascular endothelial luminal membrane domains was accompanied by an increase in ATPase activity, suggesting a potential for functionally active P-glycoprotein. These results are the first observation that peripheral inflammatory pain leads to specific structural changes in P-glycoprotein responsible for controlling analgesic drug delivery to the CNS.

P-glycoprotein (P-gp), a drug efflux pump, is known to alter the bioavailability of antiretroviral drugs at several sites, including the brain. We have previously shown that human immunodeficiency virus-1 (HIV-1) glycoprotein 120 (gp120) induces proinflammatory cytokine secretion and decreases P-gp functional expression in rat astrocytes, a cellular reservoir of HIV-1. However, whether P-gp is regulated in a similar way in human astrocytes is unknown. This study investigates the regulation of P-gp in an in vitro model of gp120-triggered human fetal astrocytes (HFAs). In this system, elevated levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α were detected in culture supernatants. Pretreatment with CCR5 neutralizing antibody attenuated cytokine secretion, suggesting that gp120-CCR5 interaction mediated cytokine production. Treatment with gp120 (R5-tropic) resulted in reduced P-gp expression (64%) and function as determined by increased (1.6-fold) cellular accumulation of [(3) H]digoxin, a P-gp substrate. Exposure to R5 or R5/X4-tropic viral isolates led to a downregulation in P-gp expression (75% or 90%, respectively), and treatment with IL-6 also showed lower P-gp expression (50%). Moreover, IL-6 neutralizing antibody blocked gp120-mediated P-gp downregulation, suggesting that IL-6 is a key modulator of P-gp. Gp120- or IL-6-mediated downregulation of P-gp was attenuated by SN50 (a nuclear factor-κB [NF-κB] inhibitor), suggesting involvement of NF-κB signaling in P-gp regulation. Our results suggest that, similarly to the case with rodent astrocytes, pathophysiological stressors associated with brain HIV-1 infection have a downregulatory effect on P-gp functional expression in human astrocytes, which may ultimately result in altered antiretroviral drug accumulation within brain parenchyma.

Reactions to caregiving and depression affect a carer's ability to continue in their caring role. This paper examines the relationship between reactions to caregiving and depression in carers of frail, older people and is a cross-sectional study of carers of community-living people (≥70 years), identified as frail, who completed a postal questionnaire. Reactions to caregiving were evaluated using the Caregiver Reaction Assessment. Anxiety and depression symptoms were measured using the Hospital Anxiety and Depression Scale. Borderline depressive symptoms were reported in 15% of carers, and 10% had abnormal depressive symptoms. Anxiety symptoms in the carers were slightly higher at 24% and 12%, respectively. Multiple regression indicated that the impact on carers' daily schedules (β = 1.419, P = 0.001; β = 1.162, P = 0.025) and their health (β = 1.509, P = 0.007; β = 1.850, P = 0.006) as a result of caregiving explained 49% of the variance in carers' depressive symptoms (P

Brain human immunodeficiency virus type-1 (HIV-1) infection is associated with oxidative stress, which may lead to HIV-1 encephalitis, a chronic neurodegenerative condition. In vitro, oxidative stress can be induced in glial cells by exposure to HIV-1 envelope protein glycoprotein (gp120). Multidrug resistance proteins (Mrps) are known to efflux endogenous substrates (i.e. GSH and GSSG) involved in cellular defense against oxidative stress. Altered GSH/GSSG export may contribute to oxidative damage during HIV-1 encephalitis. At present, it is unknown if gp120 exposure can alter the functional expression of Mrp isoforms. Heat-shock protein 70, inducible nitric oxide synthase, intracellular GSSG, 2',7'-dichlorofluorescein fluorescence, and extracellular nitrite were increased in primary cultures of rat astrocytes triggered with gp120, suggesting an oxidative stress response. RT-PCR and immunoblot analysis demonstrated increased Mrp1 mRNA (2.3-fold) and protein (2.2-fold), respectively, in gp120 treated astrocytes while Mrp4 mRNA or protein expression was not changed. Cellular retention of 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein, an established Mrp substrate, was reduced (twofold) in gp120-treated astrocytes, suggesting increased Mrp-mediated transport. In addition, GSH and GSSG export were enhanced in gp120-triggered cells. These data suggest that gp120 can up-regulate Mrp1, but not Mrp4, functional expression in cultured astrocytes. Our observation of increased GSH/GSSG efflux in response to gp120 treatment implies that Mrp isoforms may be involved in regulating the oxidative stress response in glial cells.

The inactivation of glycogen synthase kinase (GSK)3 has been proposed to play important roles in insulin and Wnt signalling. To define the role that inactivation of GSK3 plays, we generated homozygous knockin mice in which the protein kinase B phosphorylation sites on GSK3alpha (Ser21) and GSK3beta (Ser9) were changed to Ala. The knockin mice were viable and were not diabetic. Using these mice we show that inactivation of GSK3beta rather than GSK3alpha is the major route by which insulin activates muscle glycogen synthase. In contrast, we demonstrate that the activation of muscle glycogen synthase by contraction, the stimulation of muscle glucose uptake by insulin, or the activation of hepatic glycogen synthase by glucose do not require GSK3 phosphorylation on Ser21/Ser9. GSK3 also becomes inhibited in the Wnt-signalling pathway, by a poorly defined mechanism. In GSK3alpha/GSK3beta homozygous knockin cells, Wnt3a induces normal inactivation of GSK3, as judged by the stabilisation of beta-catenin and stimulation of Wnt-dependent transcription. These results establish the function of Ser21/Ser9 phosphorylation in several processes in which GSK3 inactivation has previously been implicated.

We investigated the cellular/subcellular localization and functional expression of P-glycoprotein, an ATP-dependent membrane-associated efflux transporter, in astrocytes, a brain parenchyma compartment that is poorly characterized for the expression of membrane drug transporters. Analyses were carried out on primary cultures of astrocytes isolated from the cerebral cortex of neonatal Wistar rats and CTX TNA2, an immortalized rat astrocyte cell line. Both cell cultures display morphological features typical of type I astrocytes. RT-PCR analysis revealed mdr1a and mdr1b mRNA in primary cultures of astrocytes and in CTX TNA2 cells. Western blot analysis using the P-glycoprotein monoclonal C219 antibody detected a single band of appropriate size in both cell systems. Immunocytochemical analysis using the monoclonal antibodies C219 and MRK16 labeled P-glycoprotein along the plasma membrane, caveolae, coated vesicles and nuclear envelope. Immunoprecipitation studies using the caveolin-1 polyclonal H-97 antibody demonstrated that P-glycoprotein is physically associated with caveolin-1 in both cell culture systems. The accumulation of [(3)H]digoxin (an established P-glycoprotein substrate) by the astrocyte cultures was significantly enhanced in the presence of standard P-glycoprotein inhibitors and an ATP depleting agent. These results demonstrate the cellular/subcellular location and functional expression of P-glycoprotein in rat astrocytes and suggest that this glial compartment may play an important role in the regulation of drug transport in the CNS.

An acid/alkali treatment which effects a fourfold purification of sporidesmin, making the sample immediately amenable to purification by preparative high-pressure liquid chromatography (h.p.I.c.), is described. The alkali treatment also removes polyphenols which have been responsible for discolouration problems in previous purification methods.