Search

Purpose: To quantify the inflammatory and renal parameters in comparative cohorts of patients undergoing surgical or endovascular repair of abdominal aortic aneurysms (AAAs). Methods: Forty-three patients (41 men; ages 58–81 years) underwent endovascular or conventional aneurysm surgery according to aortic morphology. All patients received a standard general anesthetic and had 12 serial blood and urine samples collected during the perioperative period. Samples underwent analysis for the cytokines interleukin (IL) 1β, tumor necrosis factor-alpha (TNF-α), and IL-6. White cell and platelet activation were estimated indirectly by measuring sL-selectin and 11-dehydrothromboxane B2, respectively. The urinary albumin: creatinine ratio (ACR) and N-acetyl-β-d-glucosaminidase (NAG) activity were estimated to assess renal injury. Fibrinogen and fibrinogen degradation products were calculated to assess activation of the clotting cascade. Results: Twenty-three patients underwent endovascular AAA repair and 20 had conventional surgery. Concentrations of IL-6 (p < 0.002) and TNF-α (p < 0.0004) were significantly higher in the conventional group. The ACR (p < 0.002) and urinary NAGs (p < 0.0009) were also significantly higher in this group, suggesting greater renal injury. Platelet activity was significantly greater in the endovascular group (p < 0.01), perhaps indicating thrombus organization within the aneurysm sac. Conclusions: These data suggest that the inflammatory response associated with conventional aneurysm repair is largely obviated by endovascular techniques. This may potentially translate to a lower incidence of multiple organ failure after endovascular surgery.

Background Current research has shed new light on the role of matrix metalloproteinase (MMP) 2 in the development of abdominal aortic aneurysms (AAAs). MMP-2 is a major protease in the wall of small aneurysms and is produced at increased levels by smooth muscle cells derived from AAAs compared with normal controls. In vivo, MMP-2 is produced as an inactive proenzyme that is activated predominantly by the cell membrane-bound enzyme, membrane type 1 matrix metalloproteinase (MT1-MMP). This study investigated the production of the MMP-2–MT1-MMP–tissue inhibitor of metalloproteinases (TIMP) 2 system within the wall of aortic aneurysms and in age-matched control arterial tissue. Methods Arterial tissue from four patients with aortic aneurysms and four age-matched aortic samples was examined for the production and expression of MMP-2, TIMP-2 and MT1-MMP protein using immunohistochemistry, in situ hybridization and in situ zymography. Results All components of the MMP-2–TIMP-2–MT1-MMP enzyme system were detected in the arterial wall of both aneurysm and control samples, specifically in the medial tissue. The enzymes co-localized with medial smooth muscle cells. Gelatinolytic activity was localized to elastin fibres in normal and aneurysmal aorta. Conclusion The presence of MT1-MMP within the media of arterial tissue suggests a powerful pathway for the activation of MMP-2. The localization of the MMP-2–TIMP-2–MT1-MMP enzyme system to the medial layer of the arterial wall gives support to the concept that this system may play an aetiological role in the pathogenesis of AAAs.

Background and Purpose —Acute disruption of atherosclerotic plaques precedes the onset of clinical syndromes, and studies have implicated a role for matrix metalloproteinases (MMPs) in this process. The aim of this study was to establish the character, level, and expression of MMPs in carotid plaques and to correlate this with clinical status, cerebral embolization, and histology. Methods —Plaques were obtained from 75 consecutive patients undergoing carotid endarterectomy and divided into 4 groups according to symptomatology (group 1, asymptomatic; group 2, symptomatic >6 months before surgery; group 3, symptomatic within 1 to 6 months; group 4, symptomatic within 1 month). All patients underwent preoperative and intraoperative transcranial Doppler monitoring. Plaques were subjected to histological examination and quantification of MMPs by zymography and ELISA. Results —The level of MMP-9 was significantly higher in group 4 (median 125.7 ng/mL for group 4, median P =0.003), with no difference in the levels of MMPs 1, 2, or 3. Furthermore, the MMP-9 concentration was significantly higher in plaques undergoing spontaneous embolization ( P =0.019) and those with histological evidence of plaque instability ( P Conclusions —The concentration, production, and expression of MMP-9 is significantly higher in unstable carotid plaques. If this proves to be a causal relationship, MMP-9 may be a strong candidate for pharmacotherapy aimed at stabilizing plaques and preventing stroke.

Aims:abdominal aortic aneurysms are characterised by changes in the extracellular matrix of the arterial media, in particular a reduction in elastin concentration. These changes are mediated by increased levels of endogenous matrix metalloproteinases (MMPs). Recently, calcium channel blockers have been shown to increase the proteolytic activity of MMP-2 secreted by vascular smooth muscle cells. It may therefore by hypothesised that calcium antagonists may potentiate the activity of MMPs in aneurysmal disease and thus accelerate AAA expansion. In this study, the ability of amlodipine — a calcium antagonist — to influence elastin degradation, was assessed in a previously described model of aneurysmal disease.Methods:porcine aortic segments (n = 8) were pre-incubated in exogenous pancreatic elastase for 24 h prior to culture in standard conditions for 6 days with 10 and 100 μg/l amlodipine. Control segments were cultured both with and without amlodipine and without elastase. At the termination of culture MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereological analysis of EVG stained sections.Results:gel enzymography demonstrated significantly increased MMP-9 activity in the amlodipine treated segments, median 4.218 vs. 2.809 arbitrary units (p

For several years quality assessment schemes have shown poor inter-laboratory agreement for the measurement of plasma proteins. There are many possible explanations for this phenomenon but these can be classified under three main headings: molecular heterogeneity of plasma proteins, type of assay and heterogeneity of antisera used for quantitation; and the standard(s) used to calibrate the test system.' The problem of variability due to standardization was recognized by Rowe et al. in 1970.2,3 They distributed six coded serum samples to several expert laboratories for measurement of IgG, IgA and IgM. For the same samples laboratories reported results with ratios of the highest to lowest values of 2·2-fold for IgG, 3'2-fold for IgA and 5'0-fold for IgM. When all laboratories used a common arbitrary reference standard the highest to lowest value ratios decreased to 1'36-fold for IgG, 1·17-fold for IgA and 1'31-fold for IgM. The authors proposed that greater uniformity of plasma immunoglobulin results should be achieved if the World Health Organization (WHO) International Reference Preparation for Human Serum Immunoglobulins G, A and M was in general use. Subsequently, a number of international primary and secondary reference preparations was prepared and distributed but the use of these materials did not entirely remove the problem of inter-laboratory differences in plasma protein measurement. By proposed definition," a Certified Reference Material (CRM) is a 'reference material accompanied by, or traceable to, a certificate stating the property value(s) concerned, issued by an organisation, public or private, which is generally accepted as technically competent'. Such materials are often, but not invariably, primary

Objectives:The aim of this study is to evaluate the cost-effectiveness of a patient-direct mailed advance notification letter on participants of a National Bowel Cancer Screening Program (NBCSP) in Australia, which was launched in August 2006 and offers free fecal occult blood testing to all Australians turning 50, 55, or 65 years of age in any given year.Methods:This study followed a hypothetical cohort of 50-year-old, 55-year-old, and 65-year-old patients undergoing fecal occult blood test (FOBT) screening through a decision analytic Markov model. The intervention compared two strategies: (i) advance letter, NBCSP, and FOBT compared with (ii) NBCSP and FOBT. The main outcome measures were life-years gained (LYG), quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio.Results:An advance notification screening letter would yield an additional 54 per 100,000 colorectal cancer deaths avoided compared with no letter. The estimated cost-effectiveness was $3,976 per LYG and $6,976 per QALY gained.Conclusions:An advance notification letter in the NBCSP may have a significant impact on LYG and cancer deaths avoided. It is cost-effective and offers a feasible strategy that could be rolled out across other screening program at an acceptable cost.

Rationale Almost one-third of Australians need help to travel outdoors after a stroke. Ambulation training and escorted outings are recommended as best practice in Australian clinical guidelines for stroke. Yet fewer than 20% of people with stroke receive enough of these sessions in their local community to change outcomes. Aims The Out-and-About trial aims to determine the efficacy and cost effectiveness of an implementation program to change team behavior and increase outings by people with stroke. Design A two-group cluster-randomized trial will be conducted using concealed allocation, blinded assessors, and intention-to-treat analysis. Twenty community teams and their stroke clients ( n = 300) will be recruited. Teams will be randomized to receive either the Out-and-About program or written guidelines only. Study Outcomes The primary outcome is the proportion of people with stroke receiving multiple escorted outings during therapy sessions, measured at baseline and 13 months postintervention. Secondary outcomes include number of outings and distance traveled, measured using a self-report diary at baseline and six months postbaseline, and a global positioning system after six months. Cost effectiveness will measure quality-adjusted life years and health service use, measured at baseline and six months postbaseline. Discussion A potential outcome of this study will be evidence for a costed, transferable implementation program. If successful, the program will have international relevance and transferability. Another potential outcome will be validation of a novel and objective method of measuring outdoor travel (global positioning system) to supplement self-report methods.

The Australian government recently introduced mandatory folic acid fortification of bread to reduce the incidence of neural tube defects (NTDs). The economic evaluation of this policy contained a number of limitations. This study aimed to address the limitations and to reconsider the findings. Cost-effectiveness analysis was used to assess the cost and benefits of mandatory versus voluntary folic acid fortification. Outcomes measures were quality-adjusted life-years (QALYs), lifeyears gained (LYG), avoided NTD cases, and additional severe neuropathy cases. Costs considered included industry costs and regulatory costs to the government. It was estimated that mandatory fortification would prevent 31 NTDs, whereas an additional 14 cases of severe neuropathy would be incurred. Overall, 539 LYG and 503 QALYs would be gained per year of mandatory compared with voluntary fortification. Mandatory fortification was cost-effective at A$10,723 per LYG and at A$11,485 per QALY. Probabilistic sensitivity analysis showed that at A$60,000 and A$151,000 per QALY, the probability that mandatory fortification was the most cost-effective strategy was 79% and 85%, respectively. Threshold analysis of loss of consumer choice indicated that with a compensation value above A$1.21 [assuming a willingness to pay (WTP) threshold of A$60,000 per QALY] or A$3.19 (assuming a WTP threshold of A$151,000 per statistical life-year) per capita per year mandatory fortification would not be cost-effective. Mandatory fortification was found to be cost-effective; however, inclusion of the loss of consumer choice can change this result. Even with mandatory fortification, mean folate intake will remain below the recommended NTD preventive level. © 2013 American Society for Nutrition.

Background: Life-threatening illnesses in young people are traumatic for patients and their families. Support services can help patients and families deal with various non-medical impacts of diagnosis, disease and treatment. The aim of this study was to determine which types of support are most valued by adolescents and young adults (AYA) with cancer or blood disorders and their families. Method: A discrete choice experiment (DCE). Separate experiments were conducted with AYA and their carers. Results: Completed surveys were returned by 83 patients and 78 carers. AYA preferred emotional support for themselves (either by counsellors and/or peers), emotional support for their family, financial support and assistance returning to school/work over services relating to cultural and spiritual needs. Covariate analysis indicated female AYA were more likely than males to prefer emotional support, while males were more likely to prefer assistance returning to work/school. Carers preferred emotional support for their AYA and assistance returning to school/work. Like AYA, they were indifferent about services relating to cultural and spiritual needs. Conclusion: Providing the types of support services that people prefer should maximise effectiveness. This study suggests that AYA patients require support services that included financial aid, assistance returning to work/study, emotional support for themselves and for their family. © 2012 Elsevier Ireland Ltd.

Objective: The aim of this study was to explore the views and perceptions of stakeholders about the current national health technology assessment process conducted by the Medical Services Advisory Committee (MSAC) and its role in the uptake and diffusion of new medical technologies in Australia. Methods: Data collection occurred over a nine month period (August 2008-April 2009). Twenty in-depth, semi-structured interviews were conducted with individuals from four stakeholders groups: (i) MSAC members and evaluators, (ii) academic and health technology assessment experts, (iii) medical industry representatives and (iv) medical specialists. Interviews were digitally recorded, transcribed verbatim and coded using a constant comparative method. Results: Respondents expressed a consensus opinion that the MSAC process is generally fair and transparent, and has been increasingly so over time. The process was described as " flexible" and " intuitive" yet also " idiosyncratic" due to the nature of the technologies being appraised. Approval by MSAC was generally reported to be increasingly important once a technology becomes more widely used. While successful MSAC approval was felt to be important for widespread distribution of a new technology, it was viewed more as a " facilitator of the uptake of new technologies" as opposed to a primary " driver" of technology uptake. Instead, other factors were identified as providing the actual impetus for the uptake of new technologies, with MSAC approval and reimbursement eventually helping facilitate more widespread diffusion. Conclusions: MSAC's decision making process is perceived as fair but with room for improvement. Its role in the uptake and diffusion of new medical technologies in Australia is limited. MSAC does not act as a barrier to significant market penetration of new procedures and medical technologies. However reimbursement is a trigger for increased use. © 2011 Elsevier Ireland Ltd.

Objective: Governments are increasing their focus on mandatory public health programmes following positive economic evaluations of their impact. This review aims to examine whether loss of consumer choice should be included in economic evaluations of mandatory health programmes (MHP). Method: A systematic literature review was conducted to identify economic evaluations of MHP, whether they discuss the impact on consumer choice and any methodological limitations. Results: Overall 39 economic evaluations were identified, of which 10 discussed the loss of consumer choice and 6 attempted to place a value on the loss of consumer choice. Methodological limitations included: measuring the marginal cost of compliance, unavailability of price elasticity estimates, the impact of income effects, double counting health impacts, biased willingness-to-pay responses, and "protest" responses. Overall it was found that the inclusion of the loss of consumer choice rarely impacted on the final outcome of the study. Conclusion: The impact of MHP on the loss of consumer choice has largely been ignored in economic evaluations. Its importance remains uncertain due to its infrequent inclusion and significant methodological limitations. Further research regarding which methodology is best for valuing the loss of consumer choice and whether it is important to the final implementation decision is warranted. © 2010 Elsevier Ireland Ltd.

Objective General practitioners (GPs) are the main providers of cervical screening in Australia and are crucial to the successful implementation of the National Cervical Screening Program (NCSP). This study assesses the views of GPs about the value of the Pap smear tests, their knowledge of the current screening policy, awareness of new technologies and concerns of litigation. Design A postal survey was conducted of a random sample of GPs in New South Wales, Australia. Results GPs are generally supportive of NCSP guidelines, specifically 88.5% now agree with the recommended 2 year screening interval. However, half believe the age range should be enlarged to include both older and younger patients. There are notable differences in knowledge and views between male and female GPs. Female GPs tend to support extending the age range and are more familiar with new technologies, whilst male GPs are more concerned about the legal implications of over and under-screening patients. Conclusions While the NCSP is generally well supported by GPs, there are differences in the knowledge and views of male and female GPs. This information provides a contemporary baseline from which to optimise the effectiveness of GPs as providers of cervical screening, improve the rate of appropriate utilisation and successfully implement any future changes to the national screening guidelines.

There is no reliable and safe method for measuring plasma volume in ill newborn infants. We describe an adaptation of the dye dilution technique using indocyanine green as the plasma label, which can be used in the sickest and smallest of infants with the minimum of disturbance. To avoid the need to take large volumes of blood from the infant, samples were diluted 1:1 with distilled water and pooled adult sera was used to construct the dye dilution standard curves. Eighteen preterm and fullterm infants were studied on 30 occasions. The measured plasma volume ranged between 21.4 and 106 ml/kg. Paired measurements were performed within 30-90 minutes of each other in seven infants. In five infants estimations of plasma volume were made shortly before and 30 minutes after the infusion of a known quantity of plasma. In eight out of 12 infants who had two measurements made there was close agreement between the second measured volume and the first measured volume, taking into account how much plasma had been given to or taken from the infant between the two measurements. The error ranged from 0.2 to 5.2 ml and the plasma recovery error ranged from -2.9% to +4.7%. In the remaining four infants the errors ranged from 2.1 to 9.5 ml and -14.2% to +8.8%. Errors in the measurement of plasma volume may arise as the result of sampling too early before full mixing of the dye has occurred, and there is a potential error in the measurement due to the distribution of albumin in the extracellular space in sick infants resulting in an overestimation of the plasma volume. Proposals for reducing sources of errors are discussed.

The pursuit of equity is a key objective of many health care systems, including Australia’s Medicare. Using the Household, Income and Labour Dynamics in Australia (HILDA) survey, we measured the extent of inequity in the utilisation of hospital services. We used methodology developed by the ECuity project for measuring horizontal inequity indices. We examine income-related health care inequities in both inpatient and day patient access and utilisation, whilst controlling for morbidity, demographic and socio-economic variables. The probability of hospital inpatient admission appeared equitable, but the probability of a day patient visit demonstrated a pro-rich distribution. Even more pronounced were the findings on the quantity of visits. The positive horizontal inequality indices indicate a degree of inequity favouring the rich, especially for inpatient utilisation. The pro-rich distribution of the probability of a day patient visit was associated with whether individuals held private health insurance. These results suggest that in Australia, which has a universal and comprehensive health system, the rich and poor are not treated equally according to need. Further research should investigate whether the causes of inequities lie in the preferences of individuals or the preferences of health care providers.

The aims of this paper are: to review and describe different approaches to HTA used in Australia and in other countries and to identify the features of best practice in HTA, particularly those likely to be most relevant to HTA at a local (ie state/regional) level. There are a number of well-developed models of HTA at the national and local levels. Most information about the operation of these models, particularly about the type and number of evaluations conducted, the recommendations/decisions made and the reasons for these is available for national processes, but there is much less readily available documentation about local level HTA. Most HTA processes that operate nationally and internationally can be categorised in one of three ways: guidance (provides structured information about appropriate technologies), mandatory (provides mandatory information about technologies to be implemented) and funding and implementation (provides structured evidence-based advice about which technologies should be implemented, the level of funding required to implement them and the source of these funds). The main factors which distinguish a high quality HTA process are that i) it is efficient in terms of setting priorities, the scope of the technologies to be assessed, avoidance of duplication and overall cost of the process, ii) the overall impact on utilisation and health budget is calculated as part of the HTA and iii) procedural justice occurs and is seen to occur; iv) it includes a comprehensive assessment of the impact on issues such as workforce, credentialing of providers and the ethical dimension of the technology; v) it influences decision making by being communicated appropriately and using trusted methods; vi) it influences adoption and diffusion of technology by ensuring that there is no diffusion prior to HTA, the results are incorporated into guidelines or recommendations, funding is linked to the decision, and remuneration arrangements and other characteristics of the HS facilitate the appropriate adoption and diffusion and vii) it influences health outcomes/efficiency/equity by ensuring that the methods and/or results are available and able to be used at a local level. Firm recommendations for an ideal system for HTA at the local level are not possible as much of the necessary information and evidence is not available about the strengths and weaknesses of HTA practices and processes currently in use. However, it is likely that the operation of a successful model of HTA at a local level would require the development of a central organizational unit, a process for implementing the results of HTA and, crucially, the building of capacity to support both types of activities. Additional expertise and skills will be required for both providers of HTA evaluations and for the commissioners and users of HTA.

Background: There are several perceived benefits from introducing positron emission tomography (PET) scanning into the staging of non small lung cancer (NSCLC). However, its greatest primary benefit is the role it can potential perform in reducing the number of unnecessary diagnostic examinations and futile surgeries. Objectives: To evaluate the economic impact and cost effectiveness of PET scanning in the management of potentially operable NSCLC patients using a cost-utility model. Methods: A literature review was conducted to find relevant studies and appropriate parameters to construct a decision model. Two strategies were compared. The first strategy was a conventional work up (CWU) consisting of an x-ray, a chest computer tomography (CT) scan and brochoscopy; the second strategy consisted of a CWU plus a whole body PET scan. These two strategies were applied to two sub-groups of NSCLC patients; those that had received a positive result on their CT scan and those that got a negative result on their CT scan. The cost-effectiveness of each strategy was dependent on a number of variables that were taken from a literature review. Costs were based on the Australian diagnostic related groups, a cost calculation for a chemotherapy course and values obtained from the literature. The life expectancy and utility scores were also taken from the literature and combined to create an incremental quality adjusted life year (QALY) value for PET for each of the patient groups. Results: The mean costs in CT negative and CT positive patients were lower in the CWU strategy, costing $A 20,427 and $A 23,578 per patient respectively compared to the PET strategy ($A 20,826 and $A 24,083 per patient respectively). The mean QALYs for both the CT positive and CT negative patients were higher in PET with 2.91 and 2.11 respectively compared to the CWU of 2.88 and 2.09. The incremental cost effectiveness ratio (ICER) for the CT negative strategy was $A 14,581 and $A 52,039 for the CT positive strategy. Conclusion: The PET strategy in CT negative and CT positive patients appears to be cost effective, however, there is much uncertainty surrounding this base result, particularly in CT positive patients.

General practices in England have been encouraged to introduce Advanced Access, but there is no robust evidence that this is associated with improved access in ways that matter to patients.To compare priorities and experiences of patients consulting in practices which do or do not operate Advanced Access.Patient questionnaire survey.Forty-seven practices in 12 primary care trust areas of England.Questionnaire administered when patients consulted.Of 12,825 eligible patients, 10,821 (84%) responded. Most (70%) were consulting about a problem they had had for at least 'a few weeks'. Patients obtained their current appointment sooner in Advanced Access practices, but were less likely to have been able to book in advance. They could usually see a doctor more quickly than those in control practices, but were no more satisfied overall with the appointment system. The top priority for patients was to be seen on a day of choice rather than to be seen quickly, but different patient groups had different priorities. Patients in Advanced Access practices were no more or less likely to obtain an appointment that matched their priorities than those in control practices. Patients in both types of practice experienced problems making contact by telephone.Patients are seen more quickly in Advanced Access practices, but speed of access is less important to patients than choice of appointment; this may be because most consultations are about long-standing problems. Appointment systems need to be flexible to accommodate the different needs of different patient groups.

Background: abdominal aortic aneurysms (AAA) are associated with excessive vascular matrix remodelling. Recent findings suggest a systemic overproduction of matrix metalloproteinases-2 (MMP-2) by vascular smooth muscle cells (SMC) may be pivotal aetiologically. SMC migration is facilitated by MMP mediated proteolysis of the basement membrane and extracellular matrix. Our aim was to see if enhanced MMP-2 production by these SMC exhibit increased invasion, in an in vitro model of migration. Method: SMC were derived from inferior mesenteric vein (IMV) harvested from patients undergoing aneurysm repair (n = 6) or colectomy for diverticulosis (n = 6, control). Using a modified Boy den chamber chemotaxis was measured towards platelet derived growth factor (PDGF) and foetal calf serum (FCS) and invasion through a Matrigel layer. MMP-2 production was quantified by ELISA and gelatin zymography. Results: chemoattractant studies demonstrated no difference in the effect of PDGF or FCS between the two populations of SMC. However, invasive studies demonstrated a significant increase in the number of migrating SMC isolated from IMV of AAA patients. Analysis of culture media extracts revealed that this difference was associated with a significant increase in production of MMP-2. Conclusion: SMC derived from patients with AAA demonstrate increased invasive properties when compared to a control group. Increased migration appears to be due to overproduction of MMP-2. The enhanced migratory potential of these SMC may lead to extracellular matrix remodelling and subsequent medial disruption demonstrated in the aneurysmal aorta. These data further support evidence of the proteolytic role of MMP-2 in cell migration. © 2002 Elsevier Science Ltd. All rights reserved.

Objective: Abdominal aortic aneurysms (AAAs) are associated with generalized arterial dilation, torturosity, and altered matrix composition, which suggests a generalized systemic weakness throughout the entire vasculature. The aim of this study was to determine whether this phenomenon was present in the venous tissue of patients with AAA. Methods: A segment of inferior mesenteric vein was harvested from patients who underwent aneurysm repair (n = 11) or colectomy for diverticulosis (n = 11; control). Matrix composition of the vessel was determined with stereology, and dimensions were measured with a computerized image analysis system. Stress-strain measurements were calculated with elongation of inferior mesenteric vein tissue with a tensile-testing machine. Results: Histologic examination results showed fragmentation of elastin fibers within the medial layer of venous tissue obtained from patients with AAA. The medial clastin content in tissue from patients with aneurysms was 19.4%, compared with 26.8% in the control group (P = .018). Mechanical test results revealed a significant reduction in the tensile strength from 2.885 MPa in the control group to 1.405 MPa in the AAA group (P = .007). This reduction corresponded with a significant reduction of 59% in the stiffness of the vessel, with the mean Young's modulus of elasticity in the AAA group being 2.72 MPa, compared with 5.361 MPa in the control group (P = .0005). Conclusion: Reduction in tensile strength and stiffness in venous tissue from patients with AAA was associated with disruption and reduction of the clastin content of the vein wall. These changes are analogous to those observed in the arterial aneurysmal wall and confirm the systemic nature of this disorder. Copyright © 2002 by The Society for Vascular Surgery and The American Association for Vascular Surgery.

Background Patients with abdominal aortic aneurysms (AAAs) exhibit arterial dilation and altered matrix composition throughout the vasculature. Matrix metalloproteinase-2 (MMP-2) is the dominant elastase in small AAAs, and overexpression of MMP-2 in vascular smooth muscle cells (SMCs) may be a primary etiological event in aneurysm genesis. The aim of this study was to investigate MMP-2 production in vascular tissue remote from the abdominal aorta. Methods and Results Inferior mesenteric vein (IMV) was harvested from patients undergoing aneurysm repair (n=21) or colectomy for diverticular disease (n=13, control). Matrix composition of the vessels was determined by stereological techniques. MMPs were extracted from tissue homogenates and quantified by gelatin zymography and ELISA. MMP-2, membrane type-1 MMP (MT1-MMP), and tissue inhibitor of metalloproteinases type 2 (TIMP-2) expression were determined by Northern analysis. SMCs were isolated from IMV, and the production and expression of MMP-2 and TIMP-2 in the SMC lines were quantified. Tissue homogenates and isolated inferior mesenteric SMCs from patients with aneurysms demonstrated significantly elevated MMP-2 levels, with no difference in TIMP-2 or MT1-MMP. These differences were a result of increased MMP-2 expression. Histological examination revealed fragmentation of elastin fibers within venous tissue obtained from patients with AAA and a significant depletion of the elastin within the media. In situ zymography localized elastolysis to medial SMCs. Conclusions Patients with AAA have elevated MMP-2 levels in the vasculature remote from the aorta. This finding is due to increased MMP-2 expression from SMCs, a characteristic maintained in tissue culture. These data support both the systemic nature of aneurysmal disease and a primary role of MMP-2 in aneurysm formation.

Objectives: Recent evidence has implicated matrix metalloproteinase 2 (MMP-2) in the pathogenesis of aneurysms. The aim of this study was to examine MMP-2 production and expression by aortic smooth muscle cells (SMCs) and dermal fibroblasts derived from patients with abdominal aortic aneurysms (AAAs). Methods: Aortic SMCs and dermal fibroblasts were cultured from patients with AAAs or from age-matched controls with atherosclerosis. The production of MMP and tissue inhibitor of metalloproteinase into culture media was analyzed with the use of gelatin zymography, Western blotting, and enzyme-linked immunosorbent assay. Gene expression was analyzed with Northern blotting. Results: All cells studied constitutively produced MMP-2. Aortic SMCs cultured from aneurysmal tissue expressed MMP-2 protein and messenger RNA at a significantly higher level than SMCs from controls ( P =.008). Dermal fibroblasts from patients with AAAs expressed MMP-2 at a similar level to controls. In both cell types, tissue inhibitor of metalloproteinase 2 and membrane type 1–MMP were expressed at similar levels. Conclusions: These data suggested that the regulation of MMP-2 gene expression was altered in the aortic SMCs of patients with aneurysms, but this finding was not repeated in other mesenchymal tissue. (J Vasc Surg 2000;32:575-83.)

Background Abdominal aortic aneurysms are characterized by degradation of the extracellular matrix, with a reduction in the elastin concentration of the arterial media. These changes have been linked to increased levels of endogenous metalloproteinases (MMPs) within the aorta, particularly MMP-2 and MMP-9. This provides a potential therapeutic target for pharmacological agents aimed at reducing the growth rate of small aneurysms. In this study, the ability of marimastat (an MMP inhibitor) to reduce matrix degradation was assessed in a previously described model of aneurysm disease. Methods Porcine aortic segments (n = 12) were preincubated in exogenous pancreatic elastase for 24 h before culture in standard conditions for 13 days with marimastat 10−5, 10−6 and 10−7 mol/l. Control segments were cultured both without marimastat and without elastase. At the termination of culture, MMPs were extracted from the tissue and quantified by substrate gel enzymography. The volume fractions of elastin and collagen were determined by stereological analysis of sections stained with Miller's elastin and van Gieson's stain. Results Stereological analysis demonstrated preservation of elastin in aorta treated with marimastat at 10–6 and 10–5 mol/l; this was significant at the latter concentration (P = 0·007). This was accompanied by a significant reduction in active MMP-2 activity in the samples treated with marimastat 10–5 mol/l (P < 0·01). Conclusion Marimastat significantly inhibited elastin degradation and active MMP-2 production within aortic organ cultures.

The Scalloped wings (Scl) gene of the Australian sheep blowfly, Lucilia cuprina, is shown to be the homologue of the Drosophila melanogaster Notch gene by comparison at the DNA sequence and genetic levels. A L. cuprina genomic fragment, which shows strong identity with the Notch (N) gene at the molecular level, hybridizes to the location of the Scl gene on polytene chromosomes. The two genes are functionally homologous; the dominant and recessive Notch-like phenotypes produced by mutations in the Scl gene allow these alleles to be classed as N-like or Abruptex-like. The Scl gene is under investigation as a candidate for the fitness and asymmetry Modifier (M) of diazinon resistance. We show that M affects the penetrance of wing and bristle phenotypes associated with two Scl alleles in a manner consistent with the M being an allele of Scl. In addition, we report a phenotypic interaction between the diazinon-resistance mutation, Rop-1, and the same alleles of Scl. We propose that the product of Rop-1, an esterase, may be involved in cell adhesion in developmental processes involving the Scl gene product.

Aim: To evaluate the cost-effectiveness of strategies designed to prevent falls amongst people aged 65 years and over living in the community and in residential aged-care facilities. Methods: A systematic review and meta-analysis of the literature was conducted. The pooled fall rate ratio was used in a decision analytic model that combined a Markov model and decision tree to estimate the costs and outcomes of potential interventions and/or strategies. The resulting cost per quality-adjusted life year was estimated. Results: The most cost-effective falls prevention strategy in community-dwelling older people was Tai Chi. Expedited cataract surgery and psychotropic medication withdrawal were also found to be cost-effective; however, the effectiveness of these interventions is less certain due to small numbers of trials and participants. The most cost-effective falls prevention strategies in residential aged-care facilities were medication review and vitamin D supplementation. Language: en

Background: Rupture of an abdominal aortic aneurysm (AAA) carries a mortality rate of up to 90%. Matrix metalloproteinases (MMPs) play a fundamental role in aneurysm formation. Previous studies have suggested a systemic increase in proteolysis in patients with AAAs and MMPs have been shown to be elevated in the serum of these patients. However, no study as yet has demonstrated differences in asymptomatic and ruptured aneurysms. The aim of the study was to determine the MMP profiles of serum from patients presenting for elective and emergency aneurysm repair. Methods: Samples of venous blood were obtained intraoperatively from 61 patients undergoing elective repair of nonruptured AAA (n = 50, median age 71 years), or emergency repair (n = 11, age 72) of ruptured AAA. Serum was quantified for the concentration of MMPs-1, -2, -3, -9, -13, TIMP-1 and -2 utilizing ELISA. Results: There were no significant differences in MMPs-2,-3,-13 and TIMP levels in the serum of patients with nonruptured and ruptured AAA. Serum MMP-1 levels were significantly increased in rupture (10.36 ng mL−1[IQR 5.94–15.94]versus 24.81 ng mL−1[18.14–41.39], P < 0.0001). MMP-9 levels were six times higher in serum from ruptured compared with nonruptured AAA patients (19.13 ng mL−1[9.27–34.24]versus 117.9 ng mL−1[30.43–161.8], P = 0.0015). Conclusions: These data demonstrate that the serum MMP profile of patients with ruptured aneurysms is significantly different to patients with nonruptured AAA. Extension of these data may allow prediction of rupture rates from serum MMP levels.

Background Urinary tract infections [UTIs] are very common in people with Spinal Cord Injury [SCI]. UTIs are increasingly difficult and expensive to treat as the organisms that cause them become more antibiotic resistant. Among the SCI population, there is a high rate of multi-resistant organism [MRO] colonisation. Non-antibiotic prevention strategies are needed to prevent UTI without increasing resistance. Probiotics have been reported to be beneficial in preventing UTIs in post-menopausal women in several in vivo and in vitro studies. The main aim of this study is to determine whether probiotic therapy with combinations of Lactobacillus reuteri RC-14 + Lactobacillus rhamnosus GR-1 [RC14-GR1] and/or Lactobacillus rhamnosus GG + Bifidobacterium BB-12 [LGG-BB12] are effective in preventing UTI in people with SCI compared to placebo. Method This is a multi-site randomised double-blind double-dummy placebo-controlled factorial design study conducted in New South Wales, Australia. All participants have a neurogenic bladder as a result of spinal injury. Recruitment started in April 2011. Participants are randomised to one of four arms, designed for factorial analysis of LGG-BB12 and/or RC14-GR1 v Placebo. This involves 24 weeks of daily oral treatment with RC14-GR1 + LGG-BB12, RC14-GR1 + placebo, LGG-BB12 + placebo or two placebo capsules. Randomisation is stratified by bladder management type and inpatient status. Participants are assessed at baseline, three months and six months for Short Form Health Survey [SF-36], microbiological swabs of rectum, nose and groin; urine culture and urinary catheters for subjects with indwelling catheters. A bowel questionnaire is administered at baseline and three months to assess effect of probiotics on bowel function. The primary outcome is time from randomisation to occurrence of symptomatic UTI. The secondary outcomes are change of MRO status and bowel function, quality of life and cost-effectiveness of probiotics in persons with SCI. The primary outcome will be analysed using survival analysis of factorial groups, with Cox regression modelling to test the effect of each treatment while allowing for the other, assuming no interaction effect. Hazard ratios and Kaplan-Meier survival curves will be used to summarise results. Discussion If these probiotics are shown to be effective in preventing UTI and MRO colonisation, they would be a very attractive alternative for UTI prophylaxis and for combating the increasing rate of antibiotic resistance after SCI. Trial registration Australian New Zealand Clinical Trials Registry [ACTRN 12610000512022]. Date of registration: 21 June 2010. Electronic supplementary material The online version of this article (doi:10.1186/s12894-016-0136-8) contains supplementary material, which is available to authorized users.

Vapotronics Inc. is developing the thermal inkjet (TIJ) technology used extensively in the printer industry to create a digital aerosol inhaler for the inhalation of therapeutics for local and systemic delivery. The operation of thermal inkjet printers requires generation of high temperatures and vaporization of the liquid formulation to effect droplet ejection. A study was conducted to develop formulations that would permit the generation of aerosols of therapeutic proteins without damage to the inkjet system or degradation of the proteins. Two proteins, human growth hormone and insulin, were formulated and aerosolized. The aerosol was collected and subjected to assays to compare the physicochemical and biological activities of these proteins before and after aerosolization. In each case, there was no significant changes to the proteins as a result of the aerosolization, providing evidence that TIJ can be used for aerosolizing solutions of protein therapeutics.

Recent research has confirmed that Australian children and pregnant women are mildly iodine deficient. A considerable proportion of the pregnant population is moderately to severely iodine deficient. Even subclinical hypothyroidism in the mother, occurring as a consequence of iodine deficiency, can cause irreversible brain damage in the fetus, making it essential to avoid iodine deficiency in pregnancy. The proposal of Food Standards Australia and New Zealand (FSANZ) - Mandatory Iodine Fortification for Australia (P1003) - has been implemented. FSANZ openly admits P1003 is inadequate for covering the needs of pregnant women. Therefore, health professionals and the public must be properly informed about the limitations of this proposal. Views differ about the most effective measures to prevent iodine deficiency in Australia. We propose that women planning a pregnancy, and pregnant and lactating women should be advised to take an iodine supplement. Women with pre-existing thyroid disease should exercise caution and seek medical advice before taking a supplement.

Following recent concerns about patients' inability to book appointments in advance, this study examined the relationship between the proportion of GP appointments reserved for same-day booking, and patient satisfaction with appointment systems. In a survey of 12 825 patients in 47 practices, it was found that a 10% increase in the proportion of same-day appointments was associated with an 8% reduction in the proportion of patients satisfied. Practices should be wary of increasing the level of same-day appointments to meet access targets.