Risk of persistent or recurrent cervical neoplasia in patients with 'pure' adenocarcinoma-in-situ (AIS) or mixed AIS and high-grade cervical squamous neoplasia (cervical intra-epithelial neoplasia grades 2 and 3 (CIN 2/3)): a population-based study.

OBJECTIVE: To compare outcomes of patients with pure adenocarcinoma-in-situ (AIS) and mixed AIS/CIN 2/3 lesions including the incidence of AIS persistence, recurrence and progression to adenocarcinoma. DESIGN: Retrospective cohort study. SETTING: Statewide population in Western Australia. POPULATION: Women diagnosed with AIS between 2001 and 2012. METHODS: We conducted a retrospective, population-based cohort study. MAIN OUTCOME MEASURES: De-identified linked data were utilised to ascertain the association between patient age at excisional treatment, margin status, lesion type, lesion size, and risk of persistent AIS (defined as the presence of AIS <12 months from treatment), recurrent AIS (≥12 months post-treatment), and adenocarcinoma. RESULTS: 636 patients were eligible for analysis. The mean age was 32.3 years and median follow-up interval was 2.5 years. Within the study cohort, 266 patients (41.8%) had pure AIS and 370 (58.2%) had mixed AIS/CIN 2/3. Overall, 47 patients (7.4%) had AIS persistence/recurrence and 12 (1.9%) had adenocarcinoma. Factors associated with persistence/recurrence were pure AIS (hazard ratio (HR) 2.3; 95%CI 1.28-3.94; P = 0.005), age >30 years (HR 2.1; 95%CI 1.16-3.81; P = 0.015), positive endocervical margins (HR 5.8; 95%CI 3.05-10.92; P = <0.001) and AIS lesions >8 mm (HR 2.5; 95%CI 1.00-6.20; P = 0.049). A histologically positive AIS ectocervical margin was not associated with persistence/recurrence. CONCLUSION: In this study, pure AIS was associated with greater risk of persistence/recurrence than was mixed AIS/CIN 2/3. AIS lesions >8 mm and positive endocervical margins were significant predictors for persistent or recurrent disease. TWEETABLE ABSTRACT: Pure cervical adenocarcinoma-in-situ (AIS) may have greater risk of recurrence than AIS co-existing with CIN 2/3.

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.

Comparison of cold knife cone biopsy and loop electrosurgical excision procedure in the management of cervical adenocarcinoma in situ: What is the gold standard?

OBJECTIVE: To compare the outcomes of patients with cervical adenocarcinoma in situ (ACIS) treated with cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for the treatment of cervical adenocarcinoma in situ (ACIS). STUDY DESIGN: This is a retrospective, population-based cohort study of Western Australian patients with ACIS diagnosed between 2001 and 2012. Outcomes included pathological margin status and the incidence of persistent or recurrent endocervical neoplasia (ACIS and adenocarcinoma) during follow-up (<12 months) and surveillance (≥12 months) periods. RESULTS: The study group comprised 338 patients including 107 (32%) treated initially by LEEP and 231 (68%) treated by CKC biopsy. The mean age was 33.2 years (range 18 to 76 years) and median follow-up interval was 3.6 years (range <1 year to 11.8 years). Overall, 27 (8.0%) patients had ACIS persistence/recurrence while 9 (2.7%) were diagnosed with adenocarcinoma during the follow-up and surveillance periods. No patient died of cervical cancer within the study period. There were no significant differences in the incidence of persistent and/or recurrent endocervical neoplasia according to the type of excisional procedure. Patients with positive biopsy margins were 3.4 times more likely to have disease persistence or recurrence. CONCLUSION(S): LEEP and CKC biopsy appear equally effective in the treatment of ACIS for women wishing to preserve fertility. Patients undergoing conservative management for ACIS should be closely monitored, particularly if biopsy margins are positive in initial excision specimens. Patients and their clinicians should be aware of the potential risks of residual and recurrent disease.

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.

Factors influencing patients' length of stay.

This study was conducted to evaluate the ability of AN-DRG version 3.1 to predict variation in patients' length of stay in hospital (LOS) and identify other factors that can influence the LOS by using routinely collected hospital morbidity data. A total of 18 DRGs that comprised 4,589 episodes were analysed. Multiple regression was used to model length of stay as a function of a number of independent variables. Overall only 37.6% of variation in mean length of stay could be explained. DRGs predicted 30% of the total variation. Other factors such as age, payment classification, source of referral, specialty of doctor, and ethnic group also influenced patient length of stay. It was concluded that the limited explanation was a consequence of a lack of a better indicator of severity within DRGs.

Oral health and hospitalization in Western Australian children.

Over the past 20 years, the prevalence of dental disease in Western Australian children has diminished. The causes of this significant improvement in health are associated with better care models, water fluoridation and changes in lifestyle. In this study, the authors examine the reasons for hospitalization for oral health conditions in Western Australia for the calendar year 1995 using the Health Department of WA database. A total of 3,754 episodes of care (4,395 bed days) was recorded for dental conditions. Dental caries resulted in the fifth and sixth highest number of episodes of hospitalization in preschool (1-4 years) and primary-school age (5-12 years) children respectively. Abnormal tooth eruption resulted in the highest number of episodes of hospitalization in high-school age (13-17 years) children. From the age-stratified rates of hospitalization (per 1000), non-Aboriginal children were more than twice as likely to enter hospital for dental related conditions. The primary cause of this is the 15 times higher rate of hospitalization for high-school age non-Aboriginal children which clearly reflects the greater use of services for impacted third molars by the metropolitan non-Aboriginal community. Examination of the distribution by health service region revealed the hospitalization rate was significantly less than the state average for the Kimberley, Pilbara, Northern Goldfields and Wanneroo regions. These data reflect the paucity of oral health care available to residents of these regions, particularly the northwest, and does not reflect a diminished burden of disease. Similarly, the rate of hospitalization for Aboriginal children reflects population and service delivery differences particularly in regional and remote WA. These data highlight the need to develop new strategies in oral health care to target 'at risk' groups in the community, particularly new parents of young children. The preventive measures associated with good oral health in children are clearly aligned with those for good general health and can be integrated into existing health messages.

Determinants of length of stay: implications on differential funding for rural and metropolitan hospitals.

This study analysed and compared the determinants of length of inpatient stay between the rural and metropolitan public hospitals. The investigation was based on the 1998/99 Western Australia patient discharge data. A Cox regression model was used due to the high proportion of patient transfers in the rural hospitals. It was found that several variables were associated with length of stay (LOS) variations within Diagnosis Related Groups (DRG). The method provides additional insights to hospital management and clinicians in assessing the risk of prolonged hospitalisation. From a state government perspective, a DRG payment adjustment strategy may be developed for different categories of admitted patient episodes. The analysis has implications on the formulation of differential funding rates between rural and metropolitan hospitals.

Trends and patterns of drug-caused mortality in Australia and Western Australia.

OBJECTIVE: To estimate the number of drug-caused deaths and compare patterns and trends of drug-caused mortality in Western Australia (WA) and Australia. METHOD: Aetiologic fractions were applied to mortality data for WA (1985-96) and Australia (1991-96) to estimate the number of deaths due to alcohol, tobacco and other drugs. RESULTS: Age-standardised rates (ASR) for smoking and alcohol-caused deaths fell significantly, while the ASR for deaths caused by other drugs increased significantly. About 85% of drug-caused deaths occurred among people aged 50 years and above. Tobacco-caused deaths mainly occurred among the elderly. Alcohol-caused death rates showed a minor peak in those aged 20-24 years then, from middle age, began to rise steadily, peaking in the oldest age group. However, deaths due to other drugs occurred mainly among young people, particularly those aged 25-34 years. These age differences were reflected in the person years of life lost (PYLL). People who died from other drugs lost, on average, about 31 years of life, twice as many as people who died from alcohol-caused conditions and about six times the average number of PYLL per tobacco-caused death. CONCLUSIONS: Nearly a fifth of all deaths were due to drugs and 80% of drug-caused deaths were due to tobacco smoking. The patterns and trends of drug-caused mortality in WA were similar to those Australia wide. IMPLICATIONS: Strategies highlighting the negative impact of tobacco and alcohol on health need to be maintained as well as programs which target illicit drug use.

Estimating the cost of hospital treatment for injuries using linked morbidity data.

This paper describes the analysis of injury-related linked hospital morbidity data by admissions and by individual patients in Western Australia (WA) from 1990 to 1994. Over this five-year period, there were an average of 35,385 admissions and 30,524 people admitted each year for injuries in WA. The age-standardised rates for injury-related hospital admissions and persons admitted for injuries increased significantly, by 2.4% and 1.5% per year respectively, over the five-year period. The number of admissions and the number of persons admitted peaked in the 20-24 years age group but the highest rates were among those aged 75 years and above. Injuries accounted for nearly 10% of all hospital bed day costs and cost about $50 per head of population per year. The cost of hospitalisation rose steadily from $85.2 million in 1990 to $113.6 million in 1994, the average cost being nearly $100 million per year. The average cost per injury related hospital episode was $2,748. Generally, the cost per hospital episode was higher for males and increased with age, following a similar pattern to that for the average length of stay.

The Quality of Surgical Care Project: benchmark standards of open resection for abdominal aortic aneurysm in Western Australia.

BACKGROUND: The Quality of Surgical Care Project (QSCP) was established in May 1996, to evaluate surgical outcomes and where indicated, recommend changes to improve the quality of surgical care in Western Australia (WA). The purpose of this study is to establish benchmark standards in WA for operative mortality, 5-year survival and length of stay in all patients who were surgically treated for aneurysm of the abdominal aorta (AAA) in WA. METHODS: The WA Linked Database was used to link the morbidity and mortality records of all patients admitted and surgically treated for AAA in WA from 1985 to 1994. The linked chains of de-identified hospital morbidity and death records were selected using diagnostic and procedure codes pertaining to AAA. Three groups were separated for analysis: those admitted for rupture, those admitted for elective repair, and those who were admitted to hospital as an emergency without mention of rupture but who underwent repair for AAA. Independent analysis for gender and patients 80 years or more were included in the study. Patients were excluded from the study if they were less than 55 years of age. RESULTS: A total of 1475 cases (1257 males, 218 females) were identified. The mean age in elective cases was 70.4 years in males and 72.4 years in females, and for rupture the mean ages were 71.9 and 74.8 years, respectively. Median length of stay for males was 12 days for elective cases. Admission type or age did not significantly influence length of stay. Thirty-day mortality in males was 4.4% for elective repair and 36.7% for ruptured AAA and 5-year survival was 71.7 and 47.7%, respectively. The overall case fatality rate for ruptured AAA was 79.3% which included those cases who died from rupture without being admitted to hospital. CONCLUSIONS: These community-wide data provide a realistic measure of surgical performance for open repair of AAA. The outcomes for elective and rupture repair for AAA compare favourably with standards reported by international centres of excellence. They also support the use of this procedure in patients over 80 years of age with rupture. This information can be used for ongoing audit purposes and as a benchmark for the introduction of new treatment modalities.

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.

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.

The WA Hospital Morbidity Data System: an evaluation of its performance and the impact of electronic data transfer.

The paper evaluates the performance of the Hospital Morbidity Data System, maintained by the Health Statistics Branch (HSB) of the Health Department of Western Australia (WA). The time taken to process discharge summaries was compared in the first and second halves of 1995, using the number of weeks taken to process 90% of all discharges and the percentage of records processed within four weeks as indicators of throughput. Both the hospitals and the HSB showed improvements in timeliness during the second half of the year. The paper also examines the impact of a recently introduced electronic data transfer system for WA country public hospitals on the timeliness of morbidity data. The processing time of country hospital records by the HSB was reduced to a similar time as for metropolitan hospitals, but the processing time in the hospitals increased, resulting in little improvement in total processing time.

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.

In vivo fertility of rams in relation to sperm-zona pellucida binding and sperm-zona pellucida penetration of ovine oocytes.

Sperm-zona pellucida (zona) binding and sperm-zona penetration have been suggested for use as in vitro bioassays of fertility since both are essential steps in the fertilization process. The correlations of sperm-zona binding and sperm-zona penetration with the in vivo fertility of sheep were investigated in this study. In vivo fertility was estimated from a heterospermic insemination trial using cryopreserved ram semen. Neither zona binding, zona penetration nor the ability to undergo an acrosome reaction was significantly correlated with the in vivo fertility of the rams (P = 0.78, P = 0.66, and P = 0.85, respectively). These results suggest that the zona binding and zona penetration bioassays may not be useful estimators for assessing cryopreserved ram sperm fertility.

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.

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.

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)