The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia.

This corrects the article DOI: 10.1038/bjc.2017.310.

The Effect of Vasectomy Reversal on Prostate Cancer Risk: International Meta-Analysis of 684,660 Vasectomized Men.

PURPOSE: Evidence of the effect of vasectomy on prostate cancer is conflicting with the issue of detection bias a key criticism. We examined the effect of vasectomy reversal on prostate cancer risk in a cohort of vasectomized men. Evidence of a protective effect would be consistent with a harmful effect of vasectomy on prostate cancer risk while nullifying the issue of detection bias. MATERIALS AND METHODS: Data were sourced from a total of 5 population level linked health databases in Australia, Canada and the United Kingdom. Cox proportional hazards regression analysis was used to compare the risk of prostate cancer in 9,754 men with vasectomy reversal to the risk in 684,660 with vasectomy but no reversal. Data from each jurisdiction were combined in a meta-analysis. RESULTS: The combined analysis showed no protective effect of vasectomy reversal on the incidence of prostate cancer compared to that in men with vasectomy alone (HR 0.92, 95% CI 0.70-1.21). CONCLUSIONS: These results align with those of previous studies showing no evidence of a link between vasectomy and prostate cancer.

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia.

BACKGROUND: Rural Australians have poorer survival for most common cancers, due partially to later diagnosis. Internationally, several initiatives to improve cancer outcomes have focused on earlier presentation to healthcare and timely diagnosis. We aimed to measure the effect of community-based symptom awareness and general practice-based educational interventions on the time to diagnosis in rural patients presenting with breast, prostate, colorectal or lung cancer in Western Australia. METHODS: 2 × 2 factorial cluster randomised controlled trial. Community Intervention: cancer symptom awareness campaign tailored for rural Australians. GP intervention: resource card with symptom risk assessment charts and local cancer referral pathways implemented through multiple academic detailing visits. Trial Area A received the community symptom awareness and Trial Area B acted as the community campaign control region. Within both Trial Areas general practices were randomised to the GP intervention or control. PRIMARY OUTCOME: total diagnostic interval (TDI). RESULTS: 1358 people with incident breast, prostate, colorectal or lung cancer were recruited. There were no significant differences in the median or ln mean TDI at either intervention level (community intervention vs control: median TDI 107.5 vs 92 days; ln mean difference 0.08 95% CI -0.06-0.23 P=0.27; GP intervention vs control: median TDI 97 vs 96.5 days; ln mean difference 0.004 95% CI -0.18-0.19 P=0.99). There were no significant differences in the TDI when analysed by factorial design, tumour group or sub-intervals of the TDI. CONCLUSIONS: This is the largest trial to test the effect of community campaign or GP interventions on timeliness of cancer diagnosis. We found no effect of either intervention. This may reflect limited dose of the interventions, or the limited duration of follow-up. Alternatively, these interventions do not have a measurable effect on time to cancer diagnosis.

Value of Pathology Review in a Population-based Series of Ovarian Tumors.

Ovarian neoplasia comprises a heterogenous group of tumors with distinct clinicopathologic and molecular features and therefore assessment of potential risk factors should be tumor subtype specific. As part of ongoing epidemiological investigations of ovarian neoplasia in Western Australia, we performed an initial review of original pathology reports followed, in selected cases, by reassessment of histology material to optimize accurate diagnosis. Additional immunohistochemistry, often using antibodies unavailable at the time of initial assessment, was also performed as required. From an initial cohort of 1660 cases identified through the Western Australia Cancer Registry, benign, nonepithelial, nonovarian, miscellaneous, and indeterminate cases were excluded. Also excluded were 33 cases that were reclassified as ovarian metastases rather than primary ovarian tumors. Following exclusions there remained 1321 borderline and malignant epithelial neoplasms. The diagnosis was considered accurate in 1186 cases (89.8%) based upon information in the initial pathology reports and clinical follow-up data but uncertain in 135 cases (10.2%). Histologic review was possible in 92 of the latter tumors leading to an amended diagnosis in 63 cases (68.5%). The most common types of diagnostic amendment were the reclassification of high-grade carcinomas of undifferentiated, endometrioid, or transitional appearance as high-grade serous carcinoma, and the reclassification of most carcinomas of mixed epithelial type as "pure" carcinomas. This review illustrated specific pitfalls in the diagnosis of ovarian epithelial neoplasia and helped to maintain the accuracy of the Western Australia Cancer Registry. Accurate diagnosis will optimize further epidemiological studies assessing risk factors in specific subtypes of ovarian neoplasia.

Green tea consumption and glutathione S-transferases genetic polymorphisms on the risk of adult leukemia.

PURPOSE: Green tea may have a beneficial role of inhibiting leukemia. Glutathione S-transferases (GSTs) are known to detoxify certain carcinogens. We investigated the roles of green tea consumption and polymorphisms of GSTM1, GSTT1 and GSTP1 on the risk of adult leukemia, and to determine whether the associations varied within GSTs genotypes. METHODS: A multicenter case-control study was conducted in China, 2008-2013. It comprised 442 incident, hematologically confirmed adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium and study site. Data were collected by face-to-face interview using a validated questionnaire. Genetic polymorphisms were assayed by PCR. RESULTS: An inverse association between green tea consumption and adult leukemia risk was observed. Compared with non-tea drinkers, the adjusted odds ratios (95 % confidence intervals) were 0.50 (0.27-0.93), 0.31 (0.17-0.55) and 0.53 (0.29-0.99) for those who, respectively, consumed green tea >20 years, ≥2 cups daily and dried tea leaves >1000 g annually. In assessing the associations by GSTs genotypes, risk reduction associated with green tea consumption was stronger in individuals with the GSTT1-null genotype (OR 0.24; 95 % CI 0.11-0.53) than GSTT1-normal carriers (OR 0.67; 95 % CI 0.42-1.05; P interaction = 0.02). GSTM1 and GSTP1 did not significantly modify the inverse association of leukemia with green tea. CONCLUSIONS: The results suggest that regular daily green tea consumption may reduce leukemia risk in Chinese adults regardless of GSTM1 and GSTP1 polymorphic status. The association between green tea and adult leukemia risk varied with GSTT1 genotype and highlights further study.

Alcohol consumption and risk of myelodysplastic syndromes: a case-control study.

PURPOSE: Epidemiological studies on alcohol consumption and the risk of myelodysplastic syndromes (MDS) have been inconclusive. We evaluated the association between alcohol consumption and MDS risk in a Chinese population. METHODS: A hospital-based case-control study was conducted between 2012 and 2013 in Hangzhou, China. The analysis included 208 case-control pairs. Diagnosis of MDS was confirmed according to the 2008 World Health Organization classification system. Controls were individually matched to the cases by gender, birth quinquennium, and residential locality. Information on habitual alcohol consumption, diet, and lifestyle was sought from face-to-face interview using a validated questionnaire. Odds ratios (ORs) were calculated using conditional logistic regression. RESULTS: Fewer cases (36.5 %) were classified as alcohol drinkers compared with the controls (48.6 %). Compared with abstainers, the adjusted OR for alcohol drinkers was 0.41 (95 % CI 0.21-0.80), and significant reduced risks were found for light alcohol consumption (≤12.5 g/day of ethanol) and for wine consumption, adjusted ORs (95 % CIs) being 0.27 (0.12-0.61) and 0.12 (0.02-0.79), respectively. Compared with individuals who consumed neither alcohol nor cigarettes, the reduced risk associated with light alcohol consumption was only statistically significant among non-smokers (OR 0.19, 95 % CI 0.06-0.60). CONCLUSIONS: The findings suggest a favorable role of light alcohol consumption in MDS, particularly among non-smokers.

Polymorphisms of 5,10-methylenetetrahydrofolate reductase and thymidylate synthase, dietary folate intake, and the risk of leukemia in adults.

The 5,10-methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) are critical enzymes in folate metabolism. Previous studies have reported conflicting results on the associations between MTHFR/TS polymorphisms and adult leukemia risk, which may due to the lack of information on folate intake. We investigated the risks of adult leukemia with genetic polymorphisms of folate metabolic enzymes (MTHFR C677T, A1298C, and TS) and evaluated if the associations varied by dietary folate intake from a multicenter case-control study conducted in Chinese. This study comprised 442 incident adult leukemia cases and 442 outpatient controls, individually matched to cases by gender, birth quinquennium, and study site. Genotypes were determined by a polymerase chain reaction (PCR) or PCR-based restriction fragment length polymorphism assay. Dietary folate intake was assessed by face-to-face interviews using a validated food-frequency questionnaire. The MTHFR 677TT genotype conferred a significant higher risk of leukemia in males than in females and exhibited an increased risk of acute myeloid leukemia (AML) but a decreased risk of acute lymphoblastic leukemia (ALL). The MTHFR 1298AC genotype appeared to decrease the risks of leukemia in both genders, in AML and ALL. Stratified analysis by dietary folate intake showed the increased risks of leukemia with the MTHFR 677TT and TS 2R3R/2R2R genotypes were only significant in individuals with low folate intake. A significant interaction between TS polymorphism and dietary folate intake was observed (P = 0.03). This study suggests that dietary folate intake and gender may modify the associations between MTHFR/TS polymorphisms and adult leukemia risk.

"It has to be fixed": a qualitative inquiry into perceived ADHD behaviour among affected individuals and parents in Western Australia.

BACKGROUND: The use of stimulant medication for Attention Deficit Hyperactivity Disorder (ADHD) to improve classroom behaviour and sustained concentration is well known. Achieving a better academic grade has been reported as the prime motivation for stimulant use and is an increasingly discussed topic. The proliferation of stimulant use for ADHD has been a cause for public, medical and policy concern in Australia. This paper explores individuals' perceptions of ADHD, the meaning that the diagnosis carries for them and their attitudes to stimulant medication treatment. METHODS: This qualitative study was underpinned by a social constructivist approach and involved semi-structured interviews with eight participants. The participants were parents of children with ADHD or were adults who themselves had been diagnosed with ADHD. Interviews were audiotaped, transcribed verbatim and thematically analysed. RESULTS: There were three interrelated yet contradictory overarching themes: (i) An impairment to achieving success, which can be a double-edged sword, but has to be fixed; (ii) Diagnosis as a relief that alleviates fault and acknowledges familial inheritance; (iii) Responsibility to be normal and to fit in with societal expectations. Collectively, these perceptions and meanings were powerful drivers of stimulant use. CONCLUSIONS: Paying attention to perceptions of ADHD and reasons for seeking or not seeking stimulant treatment is important when planning appropriate interventions for this condition.

Glass half full: Survival analysis of new rural doctor retention in Western Australia.

OBJECTIVE: To measure the time trends in retention of new rural doctors in Western Australia (WA) and identify factors associated with improved retention. DESIGN: Retrospective inception cohort study of the 1154 doctors first commencing rural practice in WA in 2004-2013, who provided 1222 tours of service consisting of up to eight attachments at different rural practice settings. MAIN OUTCOME MEASURE: Failure of doctor retention as evidenced by an absence from the rural medical workforce of greater than 1 year and analysed using actuarial survival methods and Cox proportional hazards regression. RESULTS: Comparing 2009-2013 with 2004-2008, there was an improvement of 10 percentage points in retention of new rural doctors at 2 years (58% versus 48% ) and 7 percentage points at 5 years (38% versus 31%). The retention failure rate ratio was 0.68 (95% CI, 0.58-0.83). The improvement at 5 years was largely attributable to gains in retention of those who began as GP registrars (37% versus 14%). Failure of doctor retention was lower in those who possessed procedural skills (RR 0.61, 95% CI, 0.47-0.78) and lower in international medical graduates than in those trained in Australia (RR 0.75, 95% CI, 0.59-0.95). CONCLUSIONS: New rural GP retention in WA has improved substantially, an observation at least consistent with government initiatives delivering a positive return. However, it remains the case that the majority of new doctors have left rural practice within 5 years of commencing their tour of service.

Diet and risk of adult leukemia: a multicenter case-control study in China.

PURPOSE: Epidemiologic studies on diet and leukemia risk have shown inconsistent results. This study examined the associations between dietary factors and the risk of adult leukemia in Chinese populations. METHODS: A multicenter case-control study was conducted in southeast and northeast China between 2008 and 2013. It included 442 incident cases with hematologically confirmed leukemia and 442 controls, individually match to cases by gender, birth quinquennium, and study site. Information on diet was sought from face-to-face interviews using a validated and reliable 103-item food frequency questionnaire. Odds ratios (ORs) and confidence intervals (CIs) were estimated by conditional logistic regression. RESULTS: Vegetables intake was associated with decreased risk of adult leukemia, with a significant dose-response relationship and adjusted OR of 0.30 (95 % CI 0.18-0.50) for the highest versus the lowest quartiles intake. Compared with non-consumers, the adjusted OR was 0.51 (95 % CI 0.29-0.93) for those who consumed milk at the highest tertile. Intakes of fruits, red meat, poultry, and fish were not associated with the risk. Dietary nutrients, including dietary fiber, carotenoids, vitamins B1, B2, and C, niacin, and folate, were significantly associated with reduced risks. Elevated risk was related to dietary intake animal fat and dietary habits with frequent intakes of fat, deep-fried, and smoked foods ( p for trend <0.05). CONCLUSIONS: Our findings suggest that diets rich in vegetables and adequate amount of milk reduce the risk of adult leukemia, whereas diets preferring fat, deep-fried, and smoked foods increase the risk in Chinese populations.

Dietary isoflavone intake is associated with a reduced risk of myelodysplastic syndromes.

Isoflavones have been suggested to have protective effects on certain cancers. However, the association of soya foods or dietary isoflavones with the risk of myelodysplastic syndromes (MDS) has not been examined. Thus, the aim of this hospital-based case-control study undertaken in China in 2012-2013 was to investigate the association between dietary isoflavone intake and MDS risk. The analysis included 208 cases aged 19-85 years with MDS and 208 controls individually matched to the cases by sex, birth quinquennium and residential locality. Information on habitual food intakes, including nine items of soya foods, was sought from in-person interviews using a validated 107-item FFQ. Dietary intakes of daidzein, genistein, glycitein and total isoflavones were estimated using the 2008 US Department of Agriculture Isoflavone Database. OR were calculated from conditional logistic regression after adjustment for potential confounding by demographics, lifestyle and dietary factors. The mean daily intake of total isoflavones was 19·0 mg in cases and 23·0 mg in controls. Dietary intake of isoflavones was inversely associated with the risk of MDS. The adjusted OR in the highest tertile compared with the lowest tertile of intake were 0·43 (95 % CI 0·21, 0·85) for daidzein, 0·36 (95 % CI 0·18, 0·74) for genistein, 0·49 (95 % CI 0·25, 0·97) for glycitein and 0·40 (95 % CI 0·20, 0·81) for total isoflavones. The findings suggest that higher dietary intake of isoflavones is associated with a reduced risk of MDS in a Chinese population.

Transposon-mediated chromosomal integration of transgenes in the parasitic nematode Strongyloides ratti and establishment of stable transgenic lines.

Genetic transformation is a potential tool for analyzing gene function and thereby identifying new drug and vaccine targets in parasitic nematodes, which adversely affect more than one billion people. We have previously developed a robust system for transgenesis in Strongyloides spp. using gonadal microinjection for gene transfer. In this system, transgenes are expressed in promoter-regulated fashion in the F1 but are silenced in subsequent generations, presumably because of their location in repetitive episomal arrays. To counteract this silencing, we explored transposon-mediated chromosomal integration of transgenes in S. ratti. To this end, we constructed a donor vector encoding green fluorescent protein (GFP) under the control of the Ss-act-2 promoter with flanking inverted tandem repeats specific for the piggyBac transposon. In three experiments, free-living Strongyloides ratti females were transformed with this donor vector and a helper plasmid encoding the piggyBac transposase. A mean of 7.9% of F1 larvae were GFP-positive. We inoculated rats with GFP-positive F1 infective larvae, and 0.5% of 6014 F2 individuals resulting from this host passage were GFP-positive. We cultured GFP-positive F2 individuals to produce GFP-positive F3 L3i for additional rounds of host and culture passage. Mean GFP expression frequencies in subsequent generations were 15.6% in the F3, 99.0% in the F4, 82.4% in the F5 and 98.7% in the F6. The resulting transgenic lines now have virtually uniform GFP expression among all progeny after at least 10 generations of passage. Chromosomal integration of the reporter transgenes was confirmed by Southern blotting and splinkerette PCR, which revealed the transgene flanked by S. ratti genomic sequences corresponding to five discrete integration sites. BLAST searches of flanking sequences against the S. ratti genome revealed integrations in five contigs. This result provides the basis for two powerful functional genomic tools in S. ratti: heritable transgenesis and insertional mutagenesis.

Association between potentially inappropriate medications from the Beers criteria and the risk of unplanned hospitalization in elderly patients.

BACKGROUND: Predisposition to adverse drug events with advancing age has led to the development of lists of potentially inappropriate medications (PIMs) to be avoided in the elderly, such as the Beers Criteria. The prevalence of Beers medications has been studied widely, but it is still unclear whether PIM use is predictive of adverse events in older people. OBJECTIVES: To examine potential associations between exposure to PIMs from the general Beers list and unplanned hospitalizations in elderly Western Australians. METHODS: Using an enhanced case-time-control design and conditional logistic regression applied to the pharmaceutical claims and other linked health data of 251 305 Western Australians aged ≥65 years (1993-2005), odds ratios for unplanned hospitalization were obtained, from which attributable fractions, number and proportion of hospitalizations associated with drug exposure were derived. RESULTS: Based on the health profiles of 383 150 hospitalized index subjects, overall PIM exposure was associated with an elevated risk of unplanned hospitalization (adjusted odds ratio = 1.18; 95% confidence interval = 1.15-1.21), this estimated risk increasing with the number of different PIMs and PIM quantity taken. Fifteen percent of unplanned hospitalizations in exposed index subjects (1980 per year) were attributed to PIM exposure. Patients taking meperidine (pethidine), nitrofurantoin, promethazine, indomethacin, and thioridazine appeared to be at particularly high risk of unplanned hospitalization, whereas temazepam, oxazepam, diazepam, digoxin, amiodarone, ferrous sulfate, and naproxen were attributed the greatest numbers of unplanned hospitalizations. CONCLUSIONS: Due caution prescribing Beers medications in the elderly seems justified, paying particular attention to PIMs listed above and to the concurrent use of multiple PIMs. Our results also support the retention of specific medications on PIM lists in future developments.

Cohort study of Western Australia computed tomography utilisation patterns and their policy implications.

BACKGROUND: Computed tomography (CT) scanning is a relatively high radiation dose diagnostic imaging modality with increasing concerns about radiation exposure burden at the population level in scientific literature. This study examined the epidemiology of adult CT utilisation in Western Australia (WA) in both the public hospital and private practice settings, and the policy implications. METHODS: Retrospective cohort design using aggregate adult CT data from WA public hospitals and Medical Benefits Schedule (MBS) (mid-2006 to mid-2012). CT scanning trends by sex, age, provider setting and anatomical areas were explored using crude CT scanning rates, age-standardised CT scanning rates and Poisson regression modelling. RESULTS: From mid-2006 to mid-2012 the WA adult CT scanning rate was 129 scans per 1,000 person-years (PY). Females were consistently scanned at a higher rate than males. Patients over 65 years presented the highest scanning rates (over 300 scans per 1,000 PY). Private practice accounted for 73% of adult CT scans, comprising the majority in every anatomical area. In the private setting females predominately held higher age-standardised CT scanning rates than males. This trend reversed in the public hospital setting. Patients over 85 years in the public hospital setting were the most likely age group CT scanned in nine of ten anatomical areas. Patients in the private practice setting aged 85+ years were relatively less prominent across every anatomical area, and the least likely age group scanned in facial bones and multiple areas CT scans. CONCLUSION: In comparison to the public hospital setting, the MBS subsidised private sector tended to service females and relatively younger patients with a more diverse range of anatomical areas, constituting the majority of CT scans performed in WA. Patient risk and subsequent burden is greater for females, lower ages and some anatomical areas. In the context of a national health system, Australia has various avenues to monitor radiation exposure levels, improve physician training and modify funding mechanisms to ensure individual and population medical radiation exposure is as low as reasonably achievable.

In vitro fertilization is associated with an increased risk of borderline ovarian tumours.

OBJECTIVES: To compare the risk of borderline ovarian tumours in women having in vitro fertilization (IVF) with women diagnosed with infertility but not having IVF. METHODS: This was a whole-population cohort study of women aged 20-44 years seeking hospital infertility treatment or investigation in Western Australia in 1982-2002. Using Cox regression, we examined the effects of IVF treatment and potential confounders on the rate of borderline ovarian tumours. Potential confounders included parity, age, calendar year, socio-economic status, infertility diagnoses including pelvic inflammatory disorders and endometriosis and surgical procedures including hysterectomy and tubal ligation. RESULTS: Women undergoing IVF had an increased rate of borderline ovarian tumours with a hazard ratio (HR) of 2.46 (95% confidence interval [CI] 1.20-5.04). Unlike invasive epithelial ovarian cancer, neither birth (HR 0.89; 95% CI 0.43-1.88) nor hysterectomy (1.02; 0.24-4.37) nor sterilization (1.48; 0.63-3.48) appeared protective and the rate was not increased in women with a diagnosis of endometriosis (HR 0.31; 95% CI 0.04-2.29). CONCLUSIONS: Women undergoing IVF treatment are at increased risk of being diagnosed with borderline ovarian tumours. Risk factors for borderline ovarian tumours appear different from those for invasive ovarian cancer.

In vitro fertilization, endometriosis, nulliparity and ovarian cancer risk.

OBJECTIVES: To examine the risk of invasive epithelial ovarian cancer in a cohort of women seeking treatment for infertility. METHODS: Using whole-population linked hospital and registry data, we conducted a cohort study of 21,646 women commencing hospital investigation and treatment for infertility in Western Australia in the years 1982-2002. We examined the effects of IVF treatment, endometriosis and parity on risk of ovarian cancer and explored potential confounding by tubal ligation, hysterectomy and unilateral oophorectomy/salpingo-oophorectomy (USO). RESULTS: Parous women undergoing IVF had no observable increase in the rate of ovarian cancer (hazard ratio [HR] 1.01; 95% confidence interval [CI] 0.35-2.90); the HR in women who had IVF and remained nulliparous was 1.76 (95% CI 0.74-4.16). Women diagnosed with endometriosis who remained nulliparous had a three-fold increase in the rate of ovarian cancer (HR 3.11; 95% CI 1.13-8.57); the HR in parous women was 1.52 (95% CI 0.34-6.75). In separate analyses, women who had a USO without hysterectomy had a four-fold increase in the rate of ovarian cancer (HR 4.23; 95% CI 1.30-13.77). Hysterectomy with or without USO appeared protective. CONCLUSIONS: There is no evidence of an increased risk of ovarian cancer following IVF in women who give birth. There is some uncertainty regarding the effect of IVF in women who remain nulliparous. Parous women diagnosed with endometriosis may have a slightly increased risk of ovarian cancer; nulliparous women have a marked increase in risk.

Population versus hospital controls in the assessment of dietary intake of isoflavone for case-control studies on cancers in China.

To assess dietary isoflavone intake between population and hospital outpatient controls and examine if cancer risks estimated for isoflavone using hospital outpatient controls would be different from those using population controls. Three parallel case-control studies on leukemia, breast, and colorectal cancers in China in 2009-2010 were conducted, using population and hospital outpatient controls to separately match 560 incident cases at a 1:1 ratio. A validated food frequency questionnaire was administered by face-to-face interview. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The 2 control groups had closely similar distributions of dietary isoflavone intake. Risk estimates for breast cancers were adjusted ORs (95% CI) of 0.39 (0.23-0.66) and 0.31 (0.18-0.55) for daidzein, 0.35 (0.20-0.61) and 0.28 (0.16-0.52) for genistein, 0.66 (0.41-1.08) and 0.53 (0.32-0.88) for glycitein, and 0.53 (0.33-0.85) and 0.43 (0.26-0.71) for total isoflavone using hospital outpatient and population controls respectively. The study found that hospital outpatient controls were comparable to population controls in measured dietary intake of isoflavone in the Chinese hospital setting.

Ascertaining invasive breast cancer cases; the validity of administrative and self-reported data sources in Australia.

BACKGROUND: Statutory State-based cancer registries are considered the 'gold standard' for researchers identifying cancer cases in Australia, but research using self-report or administrative health datasets (e.g. hospital records) may not have linkage to a Cancer Registry and need to identify cases. This study investigated the validity of administrative and self-reported data compared with records in a State-wide Cancer Registry in identifying invasive breast cancer cases. METHODS: Cases of invasive breast cancer recorded on the New South Wales (NSW) Cancer Registry between July 2004 and December 2008 (the study period) were identified for women in the 45 and Up Study. Registry cases were separately compared with suspected cases ascertained from: i) administrative hospital separations records; ii) outpatient medical service claims; iii) prescription medicines claims; and iv) the 45 and Up Study baseline survey. Ascertainment flags included diagnosis codes, surgeries (e.g. lumpectomy), services (e.g. radiotherapy), and medicines used for breast cancer, as well as self-reported diagnosis. Positive predictive value (PPV), sensitivity and specificity were calculated for flags within individual datasets, and for combinations of flags across multiple datasets. RESULTS: Of 143,010 women in the 45 and Up Study, 2039 (1.4%) had an invasive breast tumour recorded on the NSW Cancer Registry during the study period. All of the breast cancer flags examined had high specificity (>97.5%). Of the flags from individual datasets, hospital-derived 'lumpectomy and diagnosis of invasive breast cancer' and '(lumpectomy or mastectomy) and diagnosis of invasive breast cancer' had the greatest PPV (89% and 88%, respectively); the later having greater sensitivity (59% and 82%, respectively). The flag with the highest sensitivity and PPV ≥ 85% was 'diagnosis of invasive breast cancer' (both 86%). Self-reported breast cancer diagnosis had a PPV of 50% and sensitivity of 85%, and breast radiotherapy had a PPV of 73% and a sensitivity of 58% compared with Cancer Registry records. The combination of flags with the greatest PPV and sensitivity was '(lumpectomy or mastectomy) and (diagnosis of invasive breast cancer or breast radiotherapy)' (PPV and sensitivity 83%). CONCLUSIONS: In the absence of Cancer Registry data, administrative and self-reported data can be used to accurately identify cases of invasive breast cancer for sample identification, removing cases from a sample, or risk adjustment. Invasive breast cancer can be accurately identified using hospital-derived diagnosis alone or in combination with surgeries and breast radiotherapy.

Use of case-time-control design in pharmacovigilance applications: exploration with high-risk medications and unplanned hospital admissions in the Western Australian elderly.

PURPOSE: To use a case-time-control design to derive preliminary estimates of unplanned hospitalisations attributable to suspected high-risk medications in elderly Western Australians. METHODS: Using pharmaceutical claims linked to inpatient and other health records, the study applied a case-time-control design and conditional logistic regression to estimate odds ratios (ORs) for unplanned hospital admissions associated with anticoagulants, antirheumatics, opioids, corticosteroids and four major groups of cardiovascular drugs. Attributable fractions (AFs) were derived from the ORs to estimate the number and proportion of admissions associated with drug exposure. Results were compared with those obtained from a more conventional method using International Classification of Diseases (ICD) external cause codes to identify admissions related to adverse drug events. RESULTS: The study involved 1 899 699 index hospital admissions. Six of the eight drug groups were associated with an increased risk of unplanned hospitalisation, opioids (adjusted OR = 1.81, 95%CI 1.75-1.88; AF = 44.9%) and corticosteroids (1.48, 1.42-1.54; 32.2%) linked with the highest risks. For all six, the estimated number of hospitalisations attributed to the medication in the exposed was higher (two to 31-fold) when derived from the case-time-control design compared with identification from ICD codes. CONCLUSIONS: This study provides an alternative approach for identifying potentially harmful medications and suggests that the use of ICD external causes may underestimate adverse drug events. It takes drug exposure into account, can be applied to individual medications and may overcome under-reporting issues associated with conventional methods. The approach shows great potential as part of a post-marketing pharmacovigilance monitoring system in Australia and elsewhere.

Pelvic organ prolapse surgery in Western Australia: a population-based analysis of trends and peri-operative complications.

INTRODUCTION AND HYPOTHESIS: We previously described a declining rate of surgery in the treatment of pelvic organ prolapse (POP) in Western Australia. This paper builds on previous work by examining temporal trends and the post-operative risk of in-hospital complications, following first time incident prolapse surgery in a population-based cohort of women. METHODS: We investigated rates of prolapse surgery between 1988 and 2005 according to age group and concomitant procedure type for 34,509 women whose data were extracted from the WA Data Linkage System. We investigated changes over time in the demographic characteristics of women undergoing surgery and whether the presence of selected concomitant procedures increased the risk of in-hospital complications. RESULTS: During the study period, 34,509 women underwent an incident surgery for POP. Concomitant hysterectomy was performed in more than half of all surgeries (52.4 %) and a concomitant urinary incontinence (UI) surgery was noted in 25.8 %. 10.9 % of patients experienced a complication of interest, with the highest percentage of complications recorded in women who underwent multi-concomitant surgery. After controlling for age, comorbidity and time period we found that concomitant UI surgery increases in-hospital complications (OR 1.61 95 % CI 1.42-1.83) only in women who have a repair procedure (colporrhaphy and/or enterocele repair). There was no significant effect of concomitant procedures in women who underwent a combined repair and apical prolapse procedure. CONCLUSIONS: Surgery to treat prolapse is common, has low mortality and concomitant surgery only increases complications when combined with simpler prolapse surgery.