Colorectal cancer screening in Australia: an economic evaluation of a potential biennial screening program using faecal occult blood tests

Objective: To evaluate whether the introduction of a national, co-ordinated screening program using the faecal occult blood test represents 'value-for-money' from the perspective of the Australian Government as third-party funder.  Methods: The annual equivalent costs and consequences of a   biennial screening program in 'steady-state' operation were estimated for the Australian population using 1996 as the reference year. Disability-adjusted life years (DALYs) and the years of life lost (YLLs) averted, and the health service costs were modelled, based on the epidemiology and the costs of colorectal cancer in Australia together with the mortality reduction achieved in randomised controlled trials. Uncertainty in the model was examined using Monte Carlo simulation methods. Results: We estimate a minimum or 'base program' of screening those aged 55 to 69 years could avert 250 deaths per annum (95% uncertainty interval 99–400), at a gross cost of $A55 million (95% UI $A46 million to $A96 million) and a gross incremental cost-effectiveness ratio of $A17,000/DALY (95% UI $A13,000/DALY to $A52,000/DALY). Extending the program to include 70 to 74-year-olds is a more effective option (cheaper and higher health gain) than including the 50 to 54-year-olds. Conclusions: The findings of this study support the case for a national program directed at the 55 to 69-year-old age group with extension to 70 to 74-year-olds if there are sufficient resources. The pilot tests recently announced in Australia provide an important opportunity to consider the age range for screening and the sources of uncertainty, identified in the modelled evaluation, to assist decisions on implementing a full national program.

Salmoninae Commensal Bacteria Show a Positive Correlation Between Antibiotic Resistance and Mercury Resistance Profiles

Bacterial isolates from natural sites with high toxic and heavy metal contamination more frequently contain determinants for resistance to antimicrobials. Natural strains were isolated from the ingesta and external slime of Salmo salar (Linnaeus, 1758) and Salvelinusjontinalis (Mitchell, 1814). Fish specimens were acquired from Casco Bay hatcheries, Casco, ME where there is no history of antibiotic use. Seventy-nine bacterial strains, including many well-documented salmonid commensals (an association from which the fish derives no benefit), were identified using 165 rRNA gene sequencing. Mercury resistant isolates were selected for initially on 25μM HgCI2. Strains were then grown at 20-24°C on Trypticase Soy Agar (TSA) plates containing 0-1000μM HgCl2 or 0-130μM Phenyl Mercuric Acetate (PMA). Mercury in the hatchery feed water due to ubiquitous non-point source deposition has selected for the mercury resistance observed in bacterial strains. Antibiotic resistance determinations, as measured by Minimum Inhibitory Concentration MIC) assays were performed on the 79 bacterial isolates using Sensititrel antimicrobial susceptibility panels. A positive linear correlation between the mercury (pMA and HgCl2) MIC's and antibiotic resistance for all observed strains was demonstrated. Conjugation experiments with Pseudomonas, Aeromonas, and Azomonas donors confirmed phenotypic transfer of penicillin and cephem resistances to Escherichia coli DH5a recipients. Conjugation experiments with Pseudomonas donors showed minimal transfer of tetracycline and minoglycoside resistances to Escherichia coli DH5a recipients. Our study suggests that the accumulation of antimicrobial resistances observed in these natural bacterial populations may be due to the indirect selective pressure exerted by environmental mercury.

Subjective well-being as an indicator for clinical depression

The Theory of Homeostasis posits that Subjective Well-being (SWB) is regulated by a dynamic biological mechanism, assisting to maintain a positive view of life. Further, the theory suggests that clinical depression is the loss of SWB due to the defeat of this homeostatic defence system. To test this hypothesis it was predicted that people who were diagnosed as clinically depressed with the Semi-structured Clinical Interview (SCID-1/NP) based on the DSM-IV-TR Axis 1 would have a Personal Well-being Index-Adult (PWI-A) score below the normative range (70–80% of scale maximum). Following ethical approval a sample of 146 men was obtained and each was assessed on the SCID-1/NP and on the PWI-A. Subjects diagnosed as having one of several pathologies such as post traumatic stress disorder, panic disorder, social phobia and specific phobia were found to score significantly lower on the PWI-A compared to participants who received no diagnosis. However, as the data did not discriminate between currently depressed and persons with other non-depressive psychopathologies, a Receiver Operating Characteristics (ROC) curve analysis was used to explore this data further. Results indicated that the PWI-A was significantly better than guessing in discriminating clinically depressed cases, but only just so. Therefore, while this research found support for the proposition that the loss of SWB indicated clinical depression, the PWI-A is not sufficiently specific for diagnosis, nor can it be concluded that all instances of depression is the failure of SWB.

Incorporation of oxygen into the succinate co-product of iron(II) and 2-oxoglutarate dependent oxygenases from bacteria, plants and humans.

The ferrous iron and 2-oxoglutarate (2OG) dependent oxygenases catalyse two electron oxidation reactions by coupling the oxidation of substrate to the oxidative decarboxylation of 2OG, giving succinate and carbon dioxide coproducts. The evidence available on the level of incorporation of one atom from dioxygen into succinate is inconclusive. Here, we demonstrate that five members of the 2OG oxygenase family, AlkB from Escherichia coli, anthocyanidin synthase and flavonol synthase from Arabidopsis thaliana, and prolyl hydroxylase domain enzyme 2 and factor inhibiting hypoxia-inducible factor-1 from Homo sapiens all incorporate a single oxygen atom, almost exclusively derived from dioxygen, into the succinate co-product.

Does the inclusion of moderate amounts of red meat in the diet of exercising older women impact on faecal markers of bowel health, including faecal lactoferrin?

Background: High intakes of red meat may be associated with increased risk of colorectal cancer (CRC), however, to determine CRC risk, it is important to assess faecal changes related to protein and carbohydrate metabolism.

Objective: To determine the influence of three weekly meals rich in red meat as opposed to a carbohydrate control diet on faecal markers which are involved in the aetiology of CRC.

Design: Twenty post-menopausal women (aged 60-75) undertook, 3 times a week for 12 weeks, a 30 minute exercise session followed immediately by a cooked meal that was high in lean red meat, low in carbohydrate (n= 10) or low in lean red meat, high in carbohydrate (n=10). Dietary fibre intake and macronutrients were kept constant. At the beginning and end of the study, three-day faecal samples were collected and by-products of protein fermentation and carbohydrate metabolism, undigested fibre residues, and faecal output and colonic bacterial microbiota changes measured.

Outcomes: No significant differences were observed in subjects on either diet when comparing faecal output, faecal pH, other faecal markers, nor faecal lactoferrin. There was a trend observed in changes in the population of colonic microbiota using FISH analysis. Bacteroides spp. and Prevotella spp. appeared to decrease in women consuming a high red meat diet compared with an increase in women consuming a high carbohydrate diet.

Conclusions: In this pilot study the trend in colonic microbiota change is interesting and suggests that dietary influence of colonic microbiota, especially changes in Bacteroidetes, may be indicative of risk of gut damage and disease compared to other faecal markers.