Peter O'LEary

Purpose: Whilst computed tomography (CT) imaging has been a vital component of injury management, its increasing use has raised concern regarding ionising radiation exposure. This study aims to identify latent classes (underlying patterns) of CT use over a 3-year period following the incidence of injury and factors predicting the observed patterns. Method: A retrospective observational cohort study was conducted in 21,544 individuals aged 18 + years presenting to emergency departments (ED) of four tertiary public hospitals with new injury in Western Australia. Mixture modelling approach was used to identify latent classes of CT use over a 3-year period post injury. Results: Amongst injured people with at least one CT scan, three latent classes of CT use were identified including a: temporarily high CT use (46.4%); consistently high CT use (2.6%); and low CT use class (51.1%). Being 65 + years or older, having 3 + comorbidities, history with 3 + hospitalisations and history of CT use before injury were associated with consistently high use of CT. Injury to the head, neck, thorax or abdomen, being admitted to hospital after the injury and arriving to ED by ambulance were predictors for the temporarily high use class. Living in areas of higher socio-economic disadvantage was a unique factor associated with the low CT use class. Conclusions: Instead of assuming a single pattern of CT use for all patients with injury, the advanced latent class modelling approach has provided more nuanced understanding of the underlying patterns of CT use that may be useful for developing targeted interventions.

Background: There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening. Methods: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening. Individuals were categorized based on polygenic risk and family history of colorectal cancer. We varied screening strategies by start age, interval and test and estimated costs, and quality-adjusted life years (QALY). In our analysis, we (i) assessed the cost-effectiveness of uniform screening; (ii) developed personalized screening scenarios based on optimal screening strategies by risk group; and (iii) compared the cost-effectiveness of both. Results: At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual fecal immunochemical testing (FIT) from ages 50 to 74 years, whereas for personalized screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50 years. Although these scenarios gained the same number of QALYs (17,887), personalized screening was not cost-effective, costing an additional $428,953 due to costs associated with determining risk (assumed to be $240 per person). Personalized screening was cost-effective when these costs were less than ∼$48. Conclusions: Uniform colorectal cancer screening currently appears more cost-effective than personalized screening based on polygenic risk and family history. However, cost-effectiveness is highly dependent on the cost of determining risk. Impact: Personalized screening could become increasingly viable as costs for determining risk decrease.

Background: Contingent screening for trisomy 21 using non‐invasive prenatal testing has the potential to reduce invasive diagnostic testing and increase the detection of trisomy 21.Aim: To describe the diagnostic and economic performance of prenatal screening models for trisomy 21 that use non‐invasive prenatal testing as a contingent screen across a range of combined first trimester screening risk cut‐offs from a public health system perspective.Methods: Using a hypothetical cohort of 300 000 pregnancies, we modelled the outcomes of 25 contingent non‐invasive prenatal testing screening models and compared these to conventional screening, offering women with a high‐risk (1 > 300) combined first trimester screening result an invasive test. The 25 models used a range of risk cut‐offs. High‐risk women were offered invasive testing. Intermediate‐risk women were offered non‐invasive prenatal testing. We report the cost of each model, detection rate, costs per diagnosis, invasive tests per diagnosis and the number of fetal losses per diagnosis.Results: The cost per prenatal diagnosis of trisomy 21 using the conventional model was $51 876 compared to the contingent models which varied from $49 309–66 686. The number of diagnoses and cost per diagnosis increased as the intermediate‐risk threshold was lowered. Results were sensitive to trisomy 21 incidence, uptake of testing and cost of non‐invasive prenatal testing.Conclusion: Contingent non‐invasive prenatal testing models using more sensitive combined first trimester screening risk cut‐offs than conventional screening improved the detection rate of trisomy 21, reduced procedure‐related fetal loss and could potentially be provided at a lower cost per diagnosis than conventional screening.

Breast-fed infants may depend solely on an adequate supply of iodine in breast milk for the synthesis of thyroid hormones which are essential for optimal growth and cognitive development. This is the first study to measure breast milk iodine concentration (BMIC) among lactating women in Western Australian (n = 55). Breast milk samples were collected between 2014 and 2015 at a mean (±SD) of 38.5 (±5.5) days post-partum. The samples were analysed to determine median BMIC and the percentage of samples with a BMIC < 100 µg/L, a level considered adequate for breast-fed infants. The influence of (a) iodine-containing supplements and iodised salt use and (b) consumption of key iodine-containing foods on BMIC was also examined. The median (p25, p75) BMIC was 167 (99, 248) µg/L and 26% of samples had a BMIC < 100 µg/L. Overall, BMIC tended to be higher with iodine-containing supplement usage (ratio 1.33, 95% confidence interval (CI) (1.04, 1.70), p = 0.030), cow’s milk consumption (ratio 1.66, 95% CI (1.23, 2.23), p = 0.002) and lower for Caucasians (ratio 0.61, 95% CI (0.45, 0.83), p = 0.002), and those with secondary school only education (ratio 0.66, 95% CI (0.46, 0.96), p = 0.030). For most women, BMIC was adequate to meet the iodine requirements of their breast-fed infants. However, some women may require the use of iodine-containing supplements or iodised salt to increase BMIC to adequate levels for optimal infant nutrition.

The TSH-T4 relationship was thought to be inverse log-linear, but recent cross-sectional studies of selected populations report a complex, non-linear relationship. The TSH-T4 relationship has not been evaluated in an unselected, community-based cohort, and there are limited data regarding clinical factors which affect it. To analyse the TSH-free T4 relationship in a community-based cohort. In a cross-sectional, retrospective study, we analysed serum TSH and free T4 concentrations from 4427 participants (55% female) in the 1994 Busselton Health Study who were not taking thyroxine. Simple linear, segmented line and non-linear regression models of log₁₀TSH on free T4 were compared for goodness of fit. All 5 log TSH-free T4 models tested (separate lines, segmented conterminal line, quartic, error function, double-sigmoid curve) fitted significantly better than a simple linear model (each P<0.01 by Vuong test). Ranking by Akaike Information Criterion indicated that the segmented conterminal line and double-sigmoid models provided best fit, followed by the error function, quartic and separate lines models. From multiple regression analysis, age tertile, current smoking and TPOAb status each significantly influenced the TSH-free T4 relationship, whereas BMI category and diabetes did not. A sex difference in the TSH-free T4 relationship was apparent only in the lower part of the free T4 reference range. In a community-based setting, the relationship between log TSH and free T4 is complex, nonlinear and influenced by age, smoking and TPOAb status.

Introduction: CIN2 has a high rate of spontaneous regression in young women and may be managed conservatively in appropriately selected patients. This study aimed to investigate health outcomes in women aged 18–24 years with biopsy‐confirmed CIN2.Material and methods: A retrospective cohort study of Western Australian women aged 18–24 years diagnosed with CIN2 on cervical biopsy from 1 January 2001 to 31 December 2010. Women who had not received treatment at ≥4 months following CIN2 diagnosis were classified as managed ‘conservatively’. Subsequent cervical cytology and/or biopsy test results were used to report lesion regression (absence of dysplasia or an epithelial lesion of lower grade than CIN2) and disease persistence (CIN2, CIN3 or ACIS).Results: Follow‐up data were available for 2417 women of whom 924 (38.2%) were ‘conservatively’ managed. In all, 152 (16.4%) conservatively managed women had a lesion more severe than CIN2 detected within 24 months of initial diagnosis, of which 144 were CIN3 and eight were ACIS. There was no statistically significant association between rates of regression and patient age, Socio‐economic Indexes for Areas or Accessibility/Remoteness Index of Australia indices. The 2‐year regression rate for CIN2 was estimated to be 59.5% (95%CI 0.5–0.6) in this cohort of women.Conclusion: In conservatively managed young women with CIN2 there was a high rate of spontaneous disease regression. Thus, excisional or ablative treatments may be avoided in selected patients who receive appropriate counseling and who are able to comply with more intensive and prolonged follow‐up requirements.