The effect of individual radiographers on rates of attendance to breast screening: a 7-year retrospective study.

AIM: To establish whether individual radiographers had significantly different rescreening rates whilst controlling for other known confounding factors. MATERIALS AND METHODS: Women aged 50-69 years were identified from a state-wide screening database at their first screening attendance during the study period (2007-2013). The radiographer performing this index screen and potential confounding factors were recorded and subsequent screening behaviour was assessed. Clients with abnormal screens and those known to have died during the time period were excluded. A univariate analysis of the data from 160,028 women was assessed using the chi-square test to compare those women who attended their next mammography with non-re-attenders. Logistic regression was used to calculate the likelihood of "re-attendance success" across a range of variables. The probability of re-attendance for 11 randomly selected radiographers was determined from the logistic regression model, whilst controlling for other variables. RESULTS: Comparison of non-re-attenders (n=49,698) with 110,330 (69%) women attending the next round of screening revealed significant differences, including radiographer (Wald statistics=1188, p<0.000) even when all other known factors were controlled. CONCLUSION: This large, population-level study demonstrates that individual radiographer factors appear to influence a women's decision to return for their next screening round. Further research is required to identify reasons for differing rescreen rates and provide education and retraining of individual radiographers as appropriate.

Onset of changes in phospholipid fatty acid composition and prostaglandin synthesis following dietary manipulation with n-6 and n-3 fatty acids in the rat.

A synthetic diet preparation supplemented with 10% by weight of either safflower oil, hydrogenated coconut oil containing 3% safflower oil, or 'max EPA' fish oil was fed to rats over a 8-week period. Serial measurements of serum fatty acids, serum thromboxane B2 and urinary prostaglandin excretion were taken during the treatment period to assess the rate of change in fatty acid composition and prostaglandin synthesis following dietary manipulation. There was no significant change in weight gain between the dietary groups during the treatment period. Significant changes in serum fatty acids occurred within 48 h of treatment, with the 'max EPA' oil group having arachidonic acid levels reduced by 23% (P less than 0.01) compared to the coconut oil group. Conversely, rats fed safflower oil had an 18% enhancement of arachidonic acid during the same time period. Whole blood synthesis of thromboxane B2 was significantly depressed (P less than 0.01) after 48 h in rats fed 'max EPA' oil compared to the safflower oil or coconut oil groups. This suppression reached a maximum of 65% (P less than 0.001) after 7 days of dietary 'max EPA' oil treatment. The safflower oil and coconut oil-fed groups showed the same levels of serum thromboxane B2 production over the treatment period. Urinary excretion of both 6-ketoprostaglandin F1 alpha and prostaglandin E2 varied significantly (P less than 0.01) between the groups after 7 days of dietary treatment. Rats fed 'max EPA' oil had depressed urinary prostanoid excretion compared to the safflower and coconut oil groups which remained very similar to each other. After the 8-week treatment period rats were killed and the phospholipid fatty acid composition and prostaglandin-generating capacity of platelets, aorta and renal tissue was examined. Prostanoid production by kidney cortex and medulla and segments of aorta was consistently suppressed in rats fed 'max EPA' oil. These observations correlated well with changes in the phospholipid fatty acid profiles in these tissues. This study shows rapid changes in serum fatty acids and thromboxane B2 generation following dietary manipulation, while changes in urinary excretion or prostanoid metabolites occur only after a longer time period.

Changes in prostanoid synthesis in response to diet and hypertension in one-kidney, one clip rats.

This study was designed to examine the effects of diets that alter prostaglandin biosynthesis on the blood pressure in one-kidney, one clip rats with established hypertension and to compare the prostanoid generating capacity of hypertensive animals with those that remained normotensive. Rats attaining blood pressures of at least 180 mm Hg within 8 weeks of nephrectomy and renal artery stenosis were paired by weight and blood pressure and then placed on either a safflower oil or a prostaglandin I2 inhibitory diet (cod liver oil-linseed oil mix) for 4 weeks. Animals with blood pressures of less than 150 mm Hg were also paired for the same two dietary regimens. Comparison between the two blood pressure groups revealed that on both dietary regimens hypertensive rats produced significantly more aortic 6-keto-prostaglandin F1 alpha and serum thromboxane B2. Rats on the cod liver oil-linseed oil diet incorporated eicosapentaenoic acid into tissue stores with a corresponding decrease in arachidonic acid and significantly impaired ability to generate serum thromboxane B2 (36%), aortic 6-keto-prostaglandin F1 alpha (65%), renal homogenate 6-keto-prostaglandin F1 alpha (64%) and prostaglandin E2 (58%), and urinary prostaglandin E2 (70%) and 6-keto-prostaglandin F1 alpha (52%). Despite these differences in prostanoid synthesizing capacity, no differences in blood pressure were observed between the safflower oil-fed rats and rats fed cod liver oil-linseed oil within either the hypertensive or normotensive groups. These results suggest that prostanoids do not play a major role in maintaining blood pressure in established one-kidney, one clip hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Dissociation of effects of dietary fatty acids on blood pressure and prostanoid metabolism in Goldblatt hypertensive rats.

To study the influence of dietary modification of prostaglandin synthesis on blood pressure regulation, the effects of dietary enrichment with linoleic acid were compared with standard rat chow in three groups of 24 rats before and after renal artery constriction and contralateral nephrectomy. Dietary supplementation with 40 energy% sunflower seed oil or linseed oil respectively caused incorporation of linoleic or linolenic acids into tissue phospholipids. Relative to the sunflower seed oil, the linseed oil diet led to inhibition of prostanoid synthesis in kidney, serum or aorta in vitro and urine in vivo. Rats on both oil-rich diets had lower blood pressures than rats on a standard diet. Thus, partial suppression of prostaglandin synthesis did not accelerate one-kidney, one clip Goldblatt hypertension, nor did sunflower oil protect against hypertension in a way that could be specifically ascribed to changes in prostaglandin synthesis.

The effect of dietary fish oil and salt on blood pressure and eicosanoid metabolism of spontaneously hypertensive rats.

This study was designed to investigate the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats under conditions of normal and elevated salt intake. Forty rats from both strains were placed on either a two-series PG inhibitory diet of Max eicosapentaenoic acid (EPA) fish oil or a control diet of saturated fat for an initial period of 4 weeks. The groups were then divided into two, so that half of each received 1.5% saline in place of their drinking water for 1 week. Blood pressure of the SHR and WKY were unaffected by dietary fat before the addition of saline, but with salt loading, the Max EPA-fed SHRs showed a mean blood pressure increase of 21 mmHg relative to the EPA-fed SHR with access to water. Rats fed EPA showed impaired ability to generate serum thromboxane (TXB2) and in the groups with access to water, diminished excretion of urinary 6-keto-PGF1 alpha and PGE2. Salt loading increased prostanoid synthesis and excretion. Spontaneously hypertensive rats had greater serum TXB2 generating capacity than WKYs, but diminished urinary PGE2 excretion in those animals with access to water. The increased blood pressure observed in the salt-loaded SHR on the Max EPA-diet may be explained by reduced PG synthesis resulting in either mild sodium retention and/or increased vascular reactivity.

An inhibitory effect of dietary polyunsaturated fatty acids on renin secretion in the isolated perfused rat kidney.

The influence of dietary modification of polyunsaturated fatty acids (PUFA) on renin secretion, renal vascular tone and prostanoid excretion was studied in isolated perfused rat kidneys under basal conditions and in response to angiotensin II. After a four-week regimen of diets enriched with safflower oil, linseed oil or saturated fat, providing 20% of total energy intake (20 energy %), the animals which were fed linseed oil showed a significant fall in the proportion of arachidonic acid in renal phospholipids and a reduction in urinary prostaglandin excretion. In comparison with the other dietary groups, linseed oil feeding also resulted in a consistently lower renal vascular tone with increasing doses of angiotensin II. Under basal conditions both the PUFA-fed groups had significantly lower renal venous renin secretion rates relative to the saturated fat-fed control group. Infusion of angiotensin II (10 ng/min) suppressed renin secretion and abolished significant differences between the groups. As both the control group and the safflower oil group excreted similar levels of urinary prostaglandins, these results suggest that dietary enrichment with 20 energy % PUFA alters renin secretion by a prostaglandin-independent mechanism and that this may contribute to the lower blood pressures observed in these animals compared with the saturated fat-fed control group.

Hospitalisation of the elderly during the last year of life: an application of record linkage in Western Australia 1985-1994.

STUDY OBJECTIVE: To measure the trend, pattern, and cost of time spent in hospital during the last year of life in Western Australia and to identify trends in the place of death. The results were compared with those reported from the Oxford Record Linkage Study. DESIGN: Mortality records for those aged 65 years and over were linked to inpatient hospital morbidity records with a date of separation within one year before death. Comparative inpatient resource utilisation was estimated using ANDRG 3.0 cost weights for Australian public hospitals. SETTING: Western Australia. PARTICIPANTS: All 68,875 persons aged 65 years and over who died between 1 January 1985 and 31 December 1994. MAIN RESULTS: Increasing proportions of all age groups (65-74, 75-84, and 85+ years) were admitted to hospital at least once in the year before death during 1985-94, but the chance of admission decreased with age. There was a trend towards a greater number of shorter admissions per person. Total bed days per person showed no significant increase, except at ages 65-74 years. Total inpatient resource utilisation during the last year of life was lowest and remained constant in those aged 85 years and over, while increasing gradually (3.7% per annum) in the younger elderly. The Western Australian population spent more time in hospital in the last year of life at ages 65-74 years, but the advanced elderly spent less time in hospital, when compared with the Oxford Region. CONCLUSIONS: Recent gains in life expectancy and higher per capita health expenditure have not been accompanied by more time spent in hospital during the last year of life at ages 75+ years. International differences between Western Australia and Oxford can be explained by differences in aged care provision.

Dietary fish oils reduce plasma levels of platelet activating factor precursor (lyso-PAF) in rats.

The object of this study was to develop an assay for platelet activating factor (PAF) in rat plasma, and to utilise this to determine the effects of dietary fish oil on PAF in normotensive and spontaneously hypertensive rats. Measurement of platelet activating factor in blood plasma has proved difficult because of its rapid hydrolysis in vivo to lyso PAF. We describe here a method based on the prior acetylation of lyso PAF extracted from plasma to PAF before bioassay using 14C-serotonin labelled platelets. The active material found in acetylated plasma extracts was characterized as PAF by its chromatographic mobility, the action of phospholipases A2, C and D and by cross-desensitization studies with rabbit platelets. Rats fed dietary fish oil ('max EPA') had significantly decreased plasma lyso-PAF levels compared to control animals fed hydrogenated coconut oil (HCO). Serum thromboxane B2 (TXB2) levels were also significantly lower in animals fed the 'max EPA' diet. Spontaneously hypertensive rats (SHR) had significantly lower plasma lyso-PAF levels than their normotensive Wistar Kyoto (WKY) controls maintained on the same diets. It is proposed that dietary alterations in PAF synthesis may influence platelet behaviour in addition to the well described effects of dietary fish oil on the proaggregatory prostanoid TXA2. Rat strain differences in lyso-PAF synthesis occur, but are unlikely to be related to the maintenance of hypertension in SHR.

Prevention of myelosuppression does not improve the therapeutic efficacy of chemo-immunotherapy.

This study was designed to investigate whether the prevention of doxorubicin (DOX) induced myelosuppression could further improve the therapeutic efficacy of chemoimmunotherapy with DOX, interleukin-2 (IL-2) and interferon gamma (IFN-gamma). The antitumour activity of systemic IL-2/IFN-gamma immunotherapy in combination with DOX administered either systemically, regionally or on ion-exchange microspheres, was assessed in WAG rats bearing hind limb solid colonic adenocarcinoma implants. Whilst the use of microspheres to transport DOX clearly avoided the myelosuppression, systemic and renal toxicity associated with the use of free DOX, it did not provide any therapeutic advantage over chemo-immunotherapy with free systemic or regional drug.

Reduced toxicity of adriamycin by incorporation into ion exchange microspheres: a therapeutic study using a rat liver tumour model.

A comparison of the systemic toxicity and therapeutic efficacy of adriamycin carrying microspheres with conventional chemotherapeutic use of adriamycin was performed using a rat liver tumour model. The drug-microspheres were administered via the gastro-duodenal artery for delivery to the liver, whilst similar quantities of free adriamycin were given by systemic intravenous or regional intra-arterial routes. Significant leukopenia, thrombocytopenia and mortality were observed in the systemically treated free drug group (P less than 0.05) with a similar trend for for myelosuppression occurring in the intra-arterial free drug group. The adriamycin-microsphere group showed no toxic side-effects despite retarding tumour growth by similar amounts to the other drug modalities. This work demonstrates a large potential for the use of adriamycin carrying ion-exchange microspheres in the treatment of human malignancy.

Immunohistochemical characterisation of immunological changes at the tumour site after chemo-immunotherapy with doxorubicin, interleukin-2 and interferon-gamma.

Chemo-immunotherapy for the treatment of cancer, whilst promising from a preclinical and clinical perspective, remains limited by a lack of clear understanding of the in vivo antitumour mechanisms of this multi modality strategy. There is now strong evidence that systemic immunological parameters do not correlate with therapeutic activity. In contrast, information on therapy related immunological change at the tumour site is scarce. Having previously demonstrated that the therapeutic activity of doxorubicin chemotherapy can be significantly augmented by the co-administration of two cytokines, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), the objective of the present study was to investigate the mechanism of action of this enhanced therapeutic activity by characterising the effect of single, double and triple agent therapy upon local tumour immune parameters. Twenty-four hours after the administration of treatment to WAG rats bearing solid tumour implants of a colonic adenocarcinoma, the extent of tumour infiltration in response to the therapy was assessed in haematoxylin and eosin stained tumour sections. Treatment with doxorubicin/IL-2/IFN-gamma or IL-2/IFN-gamma was associated with a marked augmentation of the size of the tumour infiltrate (P < 0.001), as compared to untreated tumours or to those treated with any other single or double agent combination. Phenotypic evaluation of the tumour infiltrate using immunoperoxidase stained tumour sections revealed that a considerable proportion of the infiltrating cells were T cells and macrophages, whilst B cells were not detected in significant numbers. Although this phenotypic profile was not qualitatively influenced by therapy, marked quantitative differences were observed. Most notably, tumours treated with either doxorubicin/IL-2/IFN-gamma or IL-2/IFN-gamma exhibited a significant increase in the numbers of CD25+ infiltrating cells (P < 0.001). These changes in the tumour immunological response closely paralleled the therapeutic responses described previously. Thus, the enhanced therapeutic activity of the triple agent regimen may result from a profound augmentation of the size of the tumour infiltrate, together with a similar increase in the numbers of activated infiltrating cells. This study supports the concept that the immune response within the tumour is the appropriate site for investigations into the immunological antitumour mechanisms of immunotherapy and chemo-immunotherapy.

A comparative study of the anticancer efficacy of doxorubicin carrying microspheres and liposomes using a rat liver tumour model.

Due to low efficacy of chemotherapy in the treatment of liver cancer, several methods of drug targeting have been investigated. Liposomes designed to carry cytotoxic drugs to the liver are currently under clinical evaluation. While experimental evidence shows promise, this method of drug delivery has several disadvantages that include short shelf life and poor drug delivery into tumour tissue. An alternative strategy for targeted drug delivery involving use of ion exchange microspheres may overcome these limitations while still reducing systemic toxicity and maintaining therapeutic efficacy. The purpose of this study was to determine the relative antitumour efficacy of these two drugs carrying systems in the treatment of liver cancer. Compared to controls, DOX treatment with free drug, liposomes or microspheres significantly reduced tumour growth by 56% (P < 0.001), 51% (P < 0.01) and 79% (P < 0.001) respectively. Furthermore, the DOX-microsphere treatment was significantly better than either of the other DOX treatments (53%, P < 0.05) or the sham-microsphere treated group (64%, P < 0.05). Thus, drug microspheres can increase the anti-tumour efficacy compared to either free or liposomal drug while simultaneously reducing systemic toxicity.

New findings in the fatty acid composition of individual platelet phospholipids in man after dietary fish oil supplementation.

Nine healthy male volunteers were given 15 Max EPA fish oil capsules providing 2.67 g of eicosapentaenoic acid (EPA, 20:5 omega 3) and 1.72 g of docosahexaenoic acid (DHA, 22:6 omega 3) daily for 3 wk. Measurements were taken at baseline, at the end of the fish-oil period, and at 2 and 6 wk postsupplementation. The effect of fish oil on plasma lipids and the fatty acid composition of individual platelet phospholipids was studied. In general, the proportions of 20:5 omega 3 and 22:6 omega 3 in platelet phosphoglycerides were substantially increased mainly at the expense of arachidonic acid (AA, 20:4 omega 6). A large and significant increase in the relative EPA content of phosphatidylcholine (PC) (P less than 0.001) and phosphatidylethanolamine (PE) (P less than 0.001) was noted at the end of the 3 wk supplementation. We have also shown for the first time a small but significant (P less than 0.001) incorporation of EPA in phosphatidylserine (PS). Incorporation of DHA was also detected in PC, PE and PS, whereas the relative AA content of these phospholipids was significantly reduced. Fish oil supplementation led to a significant increase of 22:5 omega 3 in PS and decreases of 20:3 omega 6 in PC and 22:4 omega 6 in PE. Postsupplementation measurements showed a gradual return of all fatty acids to baseline levels. The fatty acid composition of the phosphatidylinositol (PI) fraction remained unchanged throughout the trial period. We conclude that in humans omega 3 fatty acids are incorporated into platelet membrane phospholipid subclasses with a high degree of specificity.

Evaluation of ion-exchange microspheres as carriers for the anticancer drug doxorubicin: in-vitro studies.

A comparison study of doxorubicin loading, release characteristics and stability within sodium and hydrogen forms of ion-exchange resin microspheres has been performed. It was demonstrated that resins in the Na+ form, although having lower drug loading capacity, showed similar release profiles to resins in the H+ form but still maintain all the drug activity. Resins in the H+ form, despite having high drug loading capacity, caused drug degradation within microspheres due to their strong acidic nature. Therefore, in comparison with the H+ form, resins in the Na+ form can be considered as better carriers for doxorubicin in terms of sustaining the release of drug and maintaining drug activity. Other factors such as the degree of resin cross-linkage and drug/resin mixing time have also been examined in relation to drug loading and release characteristics. Overall, this study demonstrated the significance of the characteristics of matrix materials and their influence on the drug activity and microsphere performance in-vitro.

Improved efficacy of doxorubicin by simultaneous treatment with interferon-gamma and interleukin-2.

Doxorubicin (DOX) is a potent anticancer agent active against a wide range of human neoplasms, yet, as is characteristic of most chemotherapeutics, the treatment of cancer with DOX alone has met with only limited success. This study was designed to investigate the possibility that the therapeutic potential of DOX could be enhanced by combination with one or more biological response modifiers. Segments (1mm3) of a transplantable colonic adenocarcinoma were implanted into the hind limbs of male WAG rats (200-250g). Serial tumour measurements were taken 3 x weekly throughout the 4 week experimental period by measuring the longest and perpendicular lengths with calibrated calipers. All drug administration was via a chronic indwelling jugular catheter, commencing 12 days after tumour implant, with control animals receiving physiological saline. Treatment of animals with DOX (4.5mg/kg as a 15 minute i.v. infusion), interferon gamma (IFN-gamma) (5 x 10(5) U/kg/day bolus i.v. for 5 days) or interleukin-2 (IL-2) (1 x 10(5)U/rat/day continuous i.v. infusion for 5 days) retarded tumour growth by approximately 30% by the completion of the study period (P < 0.001). The combined administration of IFN-gamma with DOX did not significantly alter the antitumour activity of either DOX or IFN-gamma. Concurrent administration of IL-2 with DOX also showed this treatment to have no therapeutic activity over that achievable with either agent alone. However, treatment of animals with IL-2, IFN-gamma and DOX resulted in a significant increase in tumour growth inhibition compared to DOX with either single cytokine (P < 0.001) and this was achieved without any apparent increases in the gross toxicity of DOX.(ABSTRACT TRUNCATED AT 250 WORDS)

Lack of synergy between 5-fluorouracil and interferon-gamma in the treatment of malignancy in the rat.

Numerous in vivo studies have reported synergism between 5-fluorouracil (5-FU) and interferon-gamma (IFN-gamma) but this has not been the case in clinical trials. As the immunomodulatory effects of IFN may be of greater importance in vivo than its direct anti-proliferative activities, it was of interest to determine whether the myelosuppressive effects of high dose 5-FU were responsible for the lack of enhanced activity of the combined drug treatment in the clinical setting. Using an animal model, the anti-tumour activity of three doses of 5-FU (5, 10 and 20 mg/kg/day, continuous intravenous infusion of 7 days) and concurrent IFN-gamma (5 x 10(5) U/kg/day, bolus IV for 5 days) were compared to 5-FU alone. IFN-gamma treatment alone produced a significant anti-tumour response relative to control. No synergism was observed at any dose of 5-FU when combined with IFN-gamma treatment despite white blood cell counts being similar to that in the IFN-gamma group at the lowest dose of 5-FU treatment. Thus, a lack of synergism in vivo is unlikely to be due to myelosuppression resulting in diminished immune response. However, other factors such as tumour type, size and location may be important in determining the final outcome.

Public versus private hospital maternity length of stay: a gamma mixture modelling approach.

Application of a gamma mixture model to obstetrical diagnosis-related groups (DRGs) revealed heterogeneity of maternity length of stay (LOS). The proportion of long-stay subgroups identified, which can account for 30% of admissions, varied between DRGs. The burden of long-stay patients borne was estimated to be much higher in private hospitals than public hospitals for normal delivery, but vice versa for Caesarean section. Such differences highlights the impact of DRG-based casemix funding on inpatient LOS and have significant implications for health insurance companies to integrate casemix funding across the public and private sectors. The analysis also benefits hospital administrators and managers to budget expenditures accordingly.

A review of hospital medical record audits: implications for funding and training.

This paper summarises the findings of coding audits in seven hospitals and one re-audit conducted by the Health Department of Western Australia. The accuracy of the coding in the first audits, as measured by differences in AN-DRG assignment, varied from 83% to 93%. The accuracy of the coding in the re-audited hospital increased by 6% to 94.5%. The major coding problems related to incorrect abstraction of information from the medical record, inaccurate code assignment, non-application of the Australian Coding Standards, or poor documentation. On average, these coding problems resulted in a loss of nearly $400,000 per hospital per year in the surveyed hospitals.