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Abstract Anti‐tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform‐like reactions are among the most common adverse r...
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Abstract Anti‐tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform‐like reactions are among the most common adverse reactions. We retrospectively identified cases of anti‐TNF‐induced psoriasis or psoriasiform manifestations in IBD patients at a tertiary centre in Australia. A total of 10 (six females) of 270 (3.7%) IBD patients treated with anti‐TNF therapy developed drug‐induced psoriatic or psoriasiform‐like reactions: five patients were treated with infliximab and five with adalimumab; nine had Crohn disease. The time from initiation of anti‐TNF agent to onset of rash was 7.5 months on average. The most frequent distributions were the scalp (7/10) and extremities (6/10). Three patients discontinued anti‐TNF treatment with resolution of the rash. Topical treatment of the lesions allowed continued use of biological agent in the majority. Paradoxical psoriatic lesions are recognised adverse events associated with anti‐TNF therapy, but discontinuation of therapy due to dermatological complications is required only rarely, even in patients with psoriasiform lesions.
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Abstract Background There is a gap in knowledge about the kind and quality of care experienced by hospital patients at the end of their lives. Aims To document and compare the patterns in end‐of‐life care for patients dying acro...
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Abstract Background There is a gap in knowledge about the kind and quality of care experienced by hospital patients at the end of their lives. Aims To document and compare the patterns in end‐of‐life care for patients dying across a range of different medical units in an acute care hospital. Methods A retrospective observational study of consecutive adult inpatient deaths between 1 July 2010 and 30 June 2014 in four different medical units of an Australian tertiary referral hospital was performed. Units were selected on the basis of highest inpatient death rates and included medical oncology, respiratory medicine, cardiology and gastroenterology/hepatology. Results Overall, 41% of patients died with active medical treatment plans, but significantly more respiratory and cardiology patients died with ongoing treatment (46 and 75% respectively) than medical oncology and gastroenterology patients (each 27%, P < 0.05). More medical oncology and gastroenterology patients were recognised as dying (92 and 88%) compared with 72% of respiratory and only 38% of cardiology patients ( P < 0.001). Significantly, more medical oncology patients were referred to palliative care and received comfort care plans than all other patient groups. However, the rate of non‐palliative interventions given in the final 48 h was not significantly different between all four groups. Conclusions There were differences in managing the dying process between all disciplines. A possible solution to these discrepancies would be to create an integrated palliative care approach across the hospital. Improving and reducing interdisciplinary practice variations will allow more patients to have a high‐quality and safe death in acute hospitals.
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The metal ion co-ordination sites of many metalloproteins have been characterized by a variety of spectroscopic techniques and small-molecule model systems, revealing many important insights into the structural determinants of met...
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The metal ion co-ordination sites of many metalloproteins have been characterized by a variety of spectroscopic techniques and small-molecule model systems, revealing many important insights into the structural determinants of metal ion co-ordination. However, our understanding of this fundamentally and practically important phenomenon remains frustratingly simplistic; in many proteins it is essentially impossible to predict metal ion specificity and the effects of remote 'outer-shell' residues on metal ion co-ordination strength are also poorly defined. This is exemplified by our inability to explain why metalloenzymes with identical metal ion co-ordination spheres, such as the closely related orthologues of bacterial PTE (phosphotriesterase) from Agrobacterium radiobacter and Pseudomonas diminuta, display different metal ion specificity and co-ordination strength. In the present study, we present a series of PTE variants that all possess identical metal ion co-ordination spheres, yet display large differences in their metal ion co-ordination strength. Using measurement of the rates of metal ion dissociation from the active site alongside analysis of structural data obtained through X-ray crystallography, we show that 'outer-shell' residues provide essential support for the metal ion ligands, in effect buttressing them in their optimal orientation. Remote mutations appear to modulate metal ion interactions by increasing or decreasing the stabilizing effects of these networks. The present study therefore provides a description of how the greater protein fold can be modified to 'tune' the strength of metal ion co-ordination and metal ion specificity, as well as reinforcing the concept of proteins as ensembles of conformational states with unique structures and biochemical properties.
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The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral me...
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The emergence and spread of chloroquine-resistant Plasmodium falciparum malaria parasites has been a disaster for world health. Resistance is conferred by mutations in the Chloroquine Resistance Transporter (PfCRT), an integral membrane protein localized to the parasite's internal digestive vacuole. These mutations result in a marked reduction in the accumulation of chloroquine (CO) by the parasite. However, the mechanism by which this occurs is unclear. We expressed both wild-type and resistant forms of PfCRT at the surface of Xenopus laevis oocytes. The resistant form of PfCRT transported CO, whereas the wild-type protein did not. CO transport via the mutant PfCRT was inhibited by CQ analogs and by the resistance-reverser verapamil. Thus, CO resistance is due to direct transport of the drug via mutant PfCRT.
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OBJECTIVE: To establish the frequency with which anxiolytic and sedative drugs result in fatal poisonings and to examine longitudinal changes in poisoning deaths.METHOD: The number of fatal poisonings between 1983 and 1999 in Engl...
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OBJECTIVE: To establish the frequency with which anxiolytic and sedative drugs result in fatal poisonings and to examine longitudinal changes in poisoning deaths.METHOD: The number of fatal poisonings between 1983 and 1999 in England, Scotland and Wales due to a single anxiolytic or sedative drug was obtained from the Department of Health in the UK. This was divided by the number of prescriptions for these drugs in England and Scotland to derive a fatal toxicity index (FTI) of deaths per million prescriptions.RESULTS: Chloral hydrate, clomethiazole, barbiturates, and related sedatives had much higher FTIs than benzodiazepines, buspirone, zolpidem and zopiclone. There has been a substantial reduction in the annual number of deaths from sedative drug poisoning between 1983 and 1999. This has been due to a sustained reduction in prescriptions for high toxicity drugs and more recently a major reduction in temazepam deaths that coincided with the withdrawal of gelatin capsule formulations.CONCLUSION: Deathswould be expected to be further reduced if there were reduced prescriptions of high toxicity drugs - and the continuing need for short-acting barbiturates, clomethiazole and chloral hydrate should be questioned.
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In November, 2002, a randomly sampled body of citizens was brought together to participate in a deliberative poll on the issue of a bill of rights. Participation in deliberative polls is thought to cause attitude change and an inc...
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In November, 2002, a randomly sampled body of citizens was brought together to participate in a deliberative poll on the issue of a bill of rights. Participation in deliberative polls is thought to cause attitude change and an increased sense of political engagement, but the underlying processes are little understood. We surveyed poll participants before and after the poll, proposing that either exposure to information, fair treatment or identification as a poll participant would predict attitude change and engagement. None of these affected attitude change but all three predicted political engagement. Results suggested that participation in the poll increases levels of political engagement through its capacities to (a) give people an opportunity to exchange views in a respectful atmosphere and (b) create or increase a sense of connection to a relevant social group.
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AIM: To describe parent-reported prevalence and management of peanut and nut allergy in school entrant children. METHOD: A population-based, cross-sectional study in the Australian National Capital. RESULTS: Out of 3851 children, ...
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AIM: To describe parent-reported prevalence and management of peanut and nut allergy in school entrant children. METHOD: A population-based, cross-sectional study in the Australian National Capital. RESULTS: Out of 3851 children, parents reported 127 had a strong allergic reaction to peanuts and 19 to other nuts ever. Nut allergy ever prevalence was 3.8% (95% confidence interval 3.2-4.4%), and of peanut allergy ever 3.3% (2.8-3.9%). Children with nut allergy were more likely to have a general practitioner (odds ratio 2.64, 1.16-6.03), hay fever (3.78, 2.67-5.36), eczema (4.54, 3.15-6.56) and wheeze in the last 12 months (3.19, 2.22-4.59) and have been breastfed (2.68, 1.26-5.77) than those who did not. At follow up of 109 children with parent-reported allergy (75% response), 70% had diagnostic test-confirmed sensitisation, 32% had been prescribed an adrenalin autoinjector (6% had used one) and 46% were not eating peanut. Increasing severity of reported symptoms following consumption of peanut was associated with an increasing likelihood of recommended management. Based on parent report, the projected estimated diagnostic test-confirmed prevalence of peanut sensitisation was 2.4% (1.9%, 3.0%) for the entire sample. CONCLUSION: Among a highly representative sample of children at school entry, 1 in 30 parents reported their child to have a strong allergic reaction to nuts and over 1 in 50 are estimated to have diagnostic test-confirmed peanut sensitisation, based on parent report.
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AIM: To describe parent-reported prevalence and management of peanut and nut allergy in school entrant children. METHOD: A population-based, cross-sectional study in the Australian National Capital. RESULTS: Out of 3851 children, ...
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AIM: To describe parent-reported prevalence and management of peanut and nut allergy in school entrant children. METHOD: A population-based, cross-sectional study in the Australian National Capital. RESULTS: Out of 3851 children, parents reported 127 had a strong allergic reaction to peanuts and 19 to other nuts ever. Nut allergy ever prevalence was 3.8% (95% confidence interval 3.2-4.4%), and of peanut allergy ever 3.3% (2.8-3.9%). Children with nut allergy were more likely to have a general practitioner (odds ratio 2.64, 1.16-6.03), hay fever (3.78, 2.67-5.36), eczema (4.54, 3.15-6.56) and wheeze in the last 12 months (3.19, 2.22-4.59) and have been breastfed (2.68, 1.26-5.77) than those who did not. At follow up of 109 children with parent-reported allergy (75% response), 70% had diagnostic test-confirmed sensitisation, 32% had been prescribed an adrenalin autoinjector (6% had used one) and 46% were not eating peanut. Increasing severity of reported symptoms following consumption of peanut was associated with an increasing likelihood of recommended management. Based on parent report, the projected estimated diagnostic test-confirmed prevalence of peanut sensitisation was 2.4% (1.9%, 3.0%) for the entire sample. CONCLUSION: Among a highly representative sample of children at school entry, 1 in 30 parents reported their child to have a strong allergic reaction to nuts and over 1 in 50 are estimated to have diagnostic test-confirmed peanut sensitisation, based on parent report.
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Unexplained stillbirth is the largest contributor to perinatal death, accounting for one-third of stillbirths. There appears to be no increase in perinatal death rates in the pregnancies that follow an unexplained stillbirth. Howe...
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Unexplained stillbirth is the largest contributor to perinatal death, accounting for one-third of stillbirths. There appears to be no increase in perinatal death rates in the pregnancies that follow an unexplained stillbirth. However, these pregnancies have increased rates of induced labour and elective caesarean section, as well as preterm birth, low birthweight, instrumental delivery, 'fetal distress' and postpartum haemorrhage. To study the wishes for future pregnancy management in women who have suffered an unexplained stillbirth. An Internet-based survey of women after an unexplained stillbirth, seeking demographic information and reproductive history, details of management of the index stillbirth and information about their wishes for
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