Biofilm dispersal and exacerbations of cystic fibrosis lung disease.
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Publications and source records attributed to K Sanderson.
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BACKGROUND: This article is part of a project to determine the cost-effectiveness of averting the burden of disease. We used population data to investigate the costs and benefits of allocating resources to optimal treatment for asthma in adults, using a burden of disease framework. METHODS: We calculated the population burden of asthma in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented current evidence-based guidelines and the direct treatment cost-effectiveness ratio in dollarA per YLD averted for both current and optimal treatment. RESULTS: The direct treatment cost of current treatment of adult asthma in Australia was dollar A452 million and averted 25% of the burden with a cost-effectiveness ratio of dollar A14 000/YLD averted. Optimal treatment and optimal compliance would cost dollar A627 million and avert 69% of the burden with a cost-effectiveness ratio of dollar A7000/YLD averted. CONCLUSION: Implementation of optimal treatment for asthma is affordable, will be more cost-effective and will significantly decrease disability.
BACKGROUND: The present paper describes a component of a large population cost-effectiveness study that aimed to identify the averted burden and economic efficiency of current and optimal treatment for the major mental disorders. This paper reports on the findings for the anxiety disorders (panic disorder/agoraphobia, social phobia, generalized anxiety disorder, post-traumatic stress disorder and obsessive compulsive disorder). METHOD: Outcome was calculated as averted 'years lived with disability' (YLD), a population summary measure of disability burden. Costs were the direct health care costs in 1997-8 Australian dollars. The cost per YLD averted (efficiency) was calculated for those already in contact with the health system for a mental health problem (current care) and for a hypothetical optimal care package of evidence-based treatment for this same group. Data sources included the Australian National Survey of Mental Health and Well-being and published treatment effects and unit costs. RESULTS: Current coverage was around 40% for most disorders with the exception of social phobia at 21%. Receipt of interventions consistent with evidence-based care ranged from 32% of those in contact with services for social phobia to 64% for post-traumatic stress disorder. The cost of this care was estimated at dollar 400 million, resulting in a cost per YLD averted ranging from dollar 7761 for generalized anxiety disorder to dollar 34 389 for panic/agoraphobia. Under optimal care, costs remained similar but health gains were increased substantially, reducing the cost per YLD to < dollar 20 000 for all disorders. CONCLUSIONS: Evidence-based care for anxiety disorders would produce greater population health gain at a similar cost to that of current care, resulting in a substantial increase in the cost-effectiveness of treatment.
OBJECTIVE: To retrospectively assess the results of tubularized incised plate (Snodgrass) urethroplasty in a series of re-operative hypospadias repairs in children. PATIENTS AND METHODS: The study comprised a follow-up (from 1996 until 2000) of 13 patients (mean age 7.5 years, range 13 months to 27 years) who had at least one previous hypospadias repair and who then underwent a reconstruction using the Snodgrass repair. In all cases the urethroplasty was covered with an additional layer of subcutaneous tissue. The original location, associated complications and results were recorded. In some cases, the long-term follow up was conducted by telephone. RESULTS: Associated complications before the Snodgrass repair included urethral stricture in two, fistula in three and persistent chordee in one patient. The mean (range) follow-up was 22 (9-34) months. The cosmetic results were excellent, with two complications (one patient with a glans dehiscence and a urethrocutaneous fistula, and a second with meatal stenosis). The remaining patients required no further procedures and were voiding normally at the last follow-up. CONCLUSION: Excellent cosmetic and functional results can be obtained using the Snodgrass incised plate urethroplasty for re-operative hypospadias repair. Only one patient in this series had an initial operation in which the urethral plate was previously incised. Therefore, caution should be used when considering an incised plate urethroplasty in these patients.
OBJECTIVE: To retrospectively assess the use of a retroperitoneal laparoscopic approach for simple nephrectomy and adrenalectomy in children. PATIENTS AND METHODS: All retroperitoneal laparoscopic renal and adrenal procedures carried out in children and completed between 1993 and March 2000 were reviewed retrospectively. Analgesic requirements, hospital stay, complications and blood loss were reviewed. The technique is described in detail. RESULTS: Forty-eight retroperitoneal laparoscopic procedures were completed in 48 patients (mean age 5.5 years, range 0.5-16). The procedures included nephrectomy (22), nephroureterectomy (15), renal biopsy (six), cyst ablation (two) and simple adrenalectomy (three). In all, 11 procedures were undertaken in children aged < 2 years. Forty-one (91%) of the children undergoing renal procedures were discharged in < 24 h. Two patients underwent three adrenalectomies. Two children required conversion to open surgery, one undergoing a right-sided adrenalectomy and one a nephrectomy. The mean operative duration for nephrectomy and nephroureterectomy was 75 min, and for adrenalectomy was 115 min. CONCLUSION: Renal and adrenal surgery in children is a safe and rapid procedure with retroperitoneal laparoscopy. The operative duration for nephrectomy and nephroureterectomy are frequently < 1 h. In addition, laparoscopic surgery offers significant advantages in terms of cosmesis and a quicker recovery.
OBJECTIVE: The Global Burden of Disease study found mental disorders to be the world's leading cause of disability. Few studies have examined the validity of the novel approach used to estimate disability, the person trade-off preference method. This paper describes, and examines the validity of, the burden of disease person trade-off protocol. METHOD: The person trade-off provides preferences for health states (how good or bad you think it is in relation to perfect health). General practitioners (n = 20) with training in mental health provided preferences for 19 mental disorders using the person trade-off method. Descriptions for the mental disorders were derived from the average symptom severity and disability observed in the Australian National Survey of Mental Health and Wellbeing. Validity was investigated by comparison with two other methods (rating scale and rank order). RESULTS: The general practitioners found the person trade-off complex and affronting. Only a moderate concordance was observed with two validity comparisons; however, validity was significantly increased following the opportunity for group discussion among the clinicians. The disability weights were higher than those used in the global study, a possible consequence of differences in disorder descriptions. CONCLUSIONS: The present study is limited by small subject numbers and by using only one type of key informant (clinicians). While this study provided some evidence for the validity of the person trade-off, it also echoes concerns from recent commentaries about the feasibility of this method. These concerns are particularly relevant for mental disorder burden, which relies heavily on the magnitude of the disability weights. Further work is required to ensure that disability burden is validly estimated, and thus can appropriately be used to inform mental health policy.
The Escherichia coli K-12 genome (ECO) was compared with the sampled genomes of the sibling species Salmonella enterica serovars Typhimurium, Typhi and Paratyphi A (collectively referred to as SAL) and the genome of the close outgroup Klebsiella pneumoniae (KPN). There are at least 160 locations where sequences of >400 bp are absent from ECO but present in the genomes of all three SAL and 394 locations where sequences are present in ECO but close homologs are absent in all SAL genomes. The 394 sequences in ECO that do not occur in SAL contain 1350 (30.6%) of the 4405 ECO genes. Of these, 1165 are missing from both SAL and KPN. Most of the 1165 genes are concentrated within 28 regions of 10-40 kb, which consist almost exclusively of such genes. Among these regions were six that included previously identified cryptic phage. A hypothetical ancestral state of genomic regions that differ between ECO and SAL can be inferred in some cases by reference to the genome structure in KPN and the more distant relative Yersinia pestis. However, many changes between ECO and SAL are concentrated in regions where all four genera have a different structure. The rate of gene insertion and deletion is sufficiently high in these regions that the ancestral state of the ECO/SAL lineage cannot be inferred from the present data. The sequencing of other closely related genomes, such as S.bongori or Citrobacter, may help in this regard.
Why does the burden of mental disorders persist in established market economies? There are four possibilities: the burden estimates are wrong; there are no effective treatments; people do not receive treatment; or people do not receive effective treatments. Data from the Australian National Survey of Mental Health and Wellbeing about the two commonest mental disorders, generalized anxiety disorder and depression, have been used in examining these issues. The burden of mental disorders in Australia is third in importance after heart disease and cancer, and anxiety and depressive disorders account for more than half of that burden. The efficacy of treatments for both disorders has been established. However, of those surveyed, 40% with current disorders did not seek treatment in the previous year and only 45% were offered a treatment that could have been beneficial. Treatment was not predictive of disorders that remitted during the year. The burden therefore persists for two reasons: too many people do not seek treatment and, when they do, efficacious treatments are not always used effectively.
OBJECTIVES: Neurogenic inflammation is mediated via sensory peptides released from the peripheral terminals of sensory nerves and can be modulated by locally released opioid peptides at the site of injury. Endomorphins are recently discovered endogenous opioid peptides with high selectivity and affinity for the mu-opioid receptor. The aim of this study was to examine the ability of endomorphin-1 (EM-1) to modulate the inflammatory response under different injury conditions. METHODS: A vacuum-induced blister model in anaesthetised rats (nembutal 60 mg/kg i.p.) was used to examine the effect of EM-1 on the acute inflammatory response induced by; (1) electrical stimulation (ES) of the distal portion of the exposed/cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or; (2) superfusion of substance P (SP) over the blister base. In addition, the effect of EM-1 on the inflammatory response to SP was examined under acute, recurrent (repeated blister induction) and chronic (chronic sciatic nerve lesion) injury conditions. RESULTS: Prior and concomitant perfusion of EM-1 (100 microM) significantly inhibited the vascular response to ES by 58% compared to controls. EM-1 also inhibited the inflammatory response to SP (both vasodilatation and plasma extravasation) in a dose-dependent manner. Significant inhibition was achieved at 100 microM and 1 mM concentrations of EM-1. Naloxone (1 mg/kg i.v.) reversed the inhibitory effect of EM-1 on the inflammatory response to SP. EM-1 (100 microM) was equally potent in inhibiting the inflammatory response to SP under acute (34% inhibition) recurrent (39%) and chronic (42%) injury conditions. CONCLUSIONS: The current results demonstrate a greater inhibitory effect of EM-1 on the inflammatory response to electrical nerve stimulation (58% inhibition) compared to SP (34% inhibition) suggesting the involvement of both pre- and post-terminal mechanisms in the inhibitory modulatory actions of EM-1. Evidence is provided for the involvement of opioid receptors in this inhibitory effect. The results also suggest that EM-1 is equipotent in inhibiting the inflammatory response under different injury conditions.
There have been recent research developments with Antarctic prokaryotes in the areas of isolations of novel bacterial, culture collections, bioactivity screening, taxonomy, production of polyunsaturated fatty acids (PUFAs), cold-adapted enzymes and bioremediation. Research to date confirms the novelty of bacteria isolated from this extreme environment. Opportunities now exist to exploit these and other findings to develop possible new biotechnological products from Antarctic microorganisms.
This study compared intensive case management (ICM) with standard clinical case management in a well-resourced community mental health service in Australia. A total of 73 severely disabled clients of an existing clinical service were randomly allocated to either ICM (caseload 10 clients per clinician) or standard case management (caseload up to 30 clients per clinician) and followed up for 12 months. A greater proportion of clients receiving ICM showed improved social functioning, these clients had fewer psychiatric hospital admissions involving police, and were more likely to engage and remain in treatment compared to those who received standard case management. Clients receiving ICM did not show a reduction in hospitalization duration or total number of episodes. It is suggested that future studies of ICM should focus on which aspects of treatment produce positive outcomes, how they can be applied to routine clinical settings, and over what period of time outcomes are sustained.
Our past work has shown that long, flexible type IV pili (single or in bundles) are the predominant pili expressed on fecal isolates of diarrhea-associated species of Aeromonas (Aeromonas veronii biovar sobria and A. caviae). They represent a family of type IV pili which we have designated Bfp (for bundle-forming pili). Reports from Japan suggest that Bfp are intestinal colonization factors. This study presents compelling evidence to support this conclusion. Aeromonas bacteria and/or Bfp purified from a strain of A. veronii biovar sobria were shown to adhere to epithelial and intestinal cell lines, freshly isolated human enterocytes, and fresh and fixed human and rabbit intestinal tissues, as determined by light and electron microscopy and immunohistochemical detection. Removal of Bfp by mechanical means decreased adhesion to cell lines by up to 80%. Purified Bfp blocked adhesion of the test strain to intestinal cells in a dose-dependent manner. Adhesion was also blocked by the Fab fraction of anti-Bfp immunoglobulin G. Moreover, ultrastructural studies (ruthenium red staining and transmission and scanning electron microscopy) demonstrated for the first time that Aeromonas adhesion to human enterocytes is pilus mediated and suggested that Bfp may also promote colonization by forming bacterium-to-bacterium linkages. Bfp-positive isolates examined for type IV pilus-mediated twitching motility in agar and slide culture assays developed for Pseudomonas aeruginosa did not, however, exhibit this function.
OBJECTIVE: Sensory nerves mediate peripheral inflammation via the release of sensory peptides at the site of tissue injury. Using a blister model of inflammation, we have previously documented that endogenous opioids modulate chronic but not acute inflammation. Hemorphins are nonclassical opioid peptides found in the region of the beta-chain of hemoglobin (Hb). The heptapeptide hemorphin-7 is identical with residues 35-41 of the beta-chain of the human Hb. The aim of this study was to examine the effect of hemorphin-7 on the inflammatory response in acute and chronic injury models. METHODS: We have used a vacuum-induced blister model in the footpad of anaesthetized rats to induce an inflammatory response in naive skin by (a) electrical stimulation (ES) of the distal end of the cut sciatic nerve at 20 V, 5 Hz, 2 ms for 1 min or (b) superfusion of sensory peptides; substance P (SP) or calcitonin gene related peptide (CGRP) over the blister base. In addition, we examined the effect of hemorphin-7 on the inflammatory response to SP induced in a previously injured but healed skin site (recurrent injury model) and in denervated skin site due to chronic nerve lesion (chronic injury model). RESULTS: The results showed that prior and concomitant perfusion of hemorphin-7 over the blister base inhibited the acute inflammatory response to ES of the sciatic nerve at C-fibre strength in a dose-dependent manner. Significant inhibition was achieved at 20 and 200 microM concentration of hemorphin-7. When hemorphin-7 (20 microM) was perfused prior to and together with SP or CGRP (both at 1 microM), over the base of acutely induced blister in naive skin, it significantly reduced the inflammatory response to SP (both plasma extravasation and vasodilatation), but was without effect on the vasodilatation response to CGRP. Naloxone, the general opioid antagonist at (1 mg/kg i.v.) reversed the inhibitory effect of hemorphin-7 on the inflammatory response to SP. On the other hand, hemorphin-7 had no effect on the inflammatory response to SP in the recurrent injury or the chronic injury models. CONCLUSIONS: The results of this study suggest that hemorphins might play a role in inhibiting the inflammatory response in acute, but not in recurrent or chronic injury conditions. Evidence is also provided that the modulatory inhibitory effect of hemorphin-7 is mediated via activation of opioid receptor(s). The significance of this study in conjunction with our previous work, is that it raises the possibility that different endogenous inhibitory mechanisms may operate under different injury conditions - endogenous hemorphins and opioids may modulate acute and chronic inflammation, respectively.
Pseudomonas aeruginosa is not generally considered a cause of infectious diarrhoea. However, it was the predominant organism isolated from the faeces of 23 unrelated, hospital outpatients investigated in the course of a year for persistent (> 1 week duration) diarrhoea. To investigate the possible aetiological role of P. aeruginosa, these patient histories were reviewed and a selection of their faecal isolates were investigated in vitro (n > or = 10) and in vivo (n = 2) for virulence. The patients had a mean age of 60 years, were receiving antibiotics and/or had an underlying illness. Extensive microbiological investigations identified no other potential or recognized enteropathogen in the faeces of 20 of these patients. More than 40% of the isolates tested were able to adhere to HEp-2 cells and exhibited twitching motility (type IV pili), properties indicative of their ability to colonize the human intestine. Cytotoxic activity was demonstrated in bacterium-free cell supernatants of over 80% of isolates; supernatants of four isolates tested in infant mice were weakly enterotoxigenic. Two isolates intragastrically inoculated into clindamycin pre-treated rats established persistent infections and induced signs and symptoms of enteritis. Overall these findings suggest that P. aeruginosa can cause diarrhoea particularly in immunodeficient individuals.
A pilus produced by a clinical isolate of Aeromonas caviae (strain CA195) was purified and partially characterised. The Mr of the pilin was estimated to be 23 kDa by SDS-PAGE. Its N-terminal amino-acid sequence showed that it was closely related to 'bundle-forming' type IV pili purified from other Aeromonas spp. associated with gastro-enteritis and considered to be important intestinal colonisation factors. Bundle-forming pili, often with a polar location, were seen on the surface of strain CA195 which was highly adherent to HEp-2 cells. Removal of surface structures by mechanical means decreased adhesion (by > or = 50%) suggesting that these pili played some role in HEp-2 cell binding. This pilus type could prove an important marker for enteropathogenic A. caviae which appear to lack other putative virulence factors.
BACKGROUND: The Global Burden of Disease studies are important because they encompass morbidity as well as mortality. Burden due to morbidity is calculated from incidence, duration and disability. There is a dearth of epidemiological measurements of disability. METHOD: Data from a quasi-community sample (n = 1364) were analysed. Diagnoses of mental and physical disorders, and reports of disability, were based on established methods. RESULTS: The disabilities reported in mental and physical disorders were comparable. Disability was correlated with comorbidity. The disability in mental disorders was examined by three methods: pure disorders, main problem and regression. It appears that major depression and substance disorder weights were overestimated, and anxiety disorder weights were underestimated in the Global Burden of Disease studies. CONCLUSIONS: A method for disentangling the effects of concurrent comorbidity is presented. The size of burden attributed to mental disorders is of potential benefit for funding mental health services, It is important that we get the estimates right.
OBJECTIVE: The objective of this study was to compare the outcomes and costs of intensive case management with routine case management for a group of severely disabled patients with a mental illness. METHOD: A cost-effectiveness analysis was conducted alongside a randomised controlled trial. Seventy-three patients, who reside in the eastern suburbs of Sydney, were randomly allocated to either intensive or routine case management. Staff providing intensive case management and substantially lower caseloads than staff providing routine case management. The main health outcome measured was patients' level of functioning as measured by the Life Skills Profile. Costing data were collected from hospital services, mental health services, general health services, community services and informal carers. RESULTS: At 12 months, outcome and costing data were analysed on 58 patients and hospitalisation data were analysed on 68 patients. Significantly more patients in the intensive case management group remained in treatment (chi 2 = 6.00, df = 1, p < 0.01) and showed a clinically significant improvement in functioning from baseline to 12 months (chi 2 = 4.50, df = 1, p < 0.05). The mean cost per patient was $7745 more in the intensive group than in the routine group (t = 1.49, df = 56, p > 0.01) over 12 months. The cost-effectiveness ratio indicated a cost of $27,661 per year for one additional patient in the intensive case management group to make a clinically significant improvement in functioning. CONCLUSION: Intensive case management led to an increased rate of retention in treatment and a clinically significant improvement in functioning. Further comparative cost-effectiveness studies are required to determine whether $27,661 per year for one patient to make a clinically significant improvement in functioning is a cost-effective use of mental health resources.