Hierarchical models in the analysis of trends in prevalence of congenital anomalies and risks associated with first trimester medications.

PhDAbstract Background Early identification of risk factors, in particular first trimester teratogenic medications, for congenital anomalies (CAs) is essential. Despite similarities between different CAs and between different medications, current surveillance methods in Europe examine each CA and each medication separately. This thesis aims to investigate whether the use of hierarchical statistical methods combining information in groups can improve CA surveillance methods. Methods EUROCAT is a European network of population-based CA registries, with EUROmediCAT comprising those registries with additional information on medication use in pregnancy. Trends in CAs from 2003-2012 in 18 EUROCAT registries (n=81,147) were analysed using Poisson regression models considering each CA separately and using hierarchical models combining related subgroups. First trimester medication exposures from 1995-2011 in 13 EUROmediCAT registries (n=15,058) were analysed. Firstly, groupings of medications and/or CAs were considered when determining the statistical significance of each medication-CA combination, using False Discovery Rate (FDR) procedures to adjust for multiple testing. Secondly, Bayesian hierarchical models were applied to directly model the group effects. The Australian classification system for prescribing medicines in pregnancy was used to independently identify “high risk” medications. The number of “high risk” medications identified by the FDR methods and Bayesian models were compared. Results For analysis of trends, grouping EUROCAT CA subgroups using hierarchical models did not provide additional information over that obtained from independent analyses of each subgroup. The double FDR method grouping medications by ATC3 level codes performed better than other FDR methods. Use of Bayesian hierarchical models did not produce enough of an improvement to justify the increased effort of implementing such models.This work was supported by the Medical Research Council [Award reference: 1504916] and the Wolfson Institute of Preventive Medicine

Associations between commuting modes and risk of 16 site-specific cancers in the UK Biobank

Background: The choice of transport mode may influence cancer risk by affecting physical activity level, sedentary behaviour, and exposure to environmental pollution. This study investigated the associations between commuting modes and 16 site-specific cancers in the UK Biobank. Methods: The UK Biobank is a prospective cohort study involving about 500 000 participants. Information on transport modes was collected at recruitment, and incident cancer cases were identified through linkage to national cancer registries. Multivariable Cox proportional hazards models were used. Results: There were 252 334 employed participants included, and 15 828 incident cancer cases were identified over a median follow-up of 11.7 years. Compared to the car-only mode, cycling (exclusively or combined with any other modes) was associated with a lower risk of colon [hazard ratio (HR): 0.72; 95% confidence interval: 0.53–0.96], renal (HR: 0.60; 0.38–0.96), and stomach (HR: 0.27; 0.10–0.71) cancers. Walking (exclusively or combined with any motorized mode) was associated with a lower risk of renal (HR: 0.67; 0.49–0.92) and liver (HR: 0.55; 0.31–0.98) cancers. Public transport users were less engaged in other physical activities, and its use was associated with a higher risk of bladder cancer (HR: 1.39; 1.01–1.90). Conclusions: Active commuting, even combined with motorized modes, is associated with a lower risk of some common cancers

Outcomes from low-risk ductal carcinoma in situ: a systematic review and meta-analysis

Purpose: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches. Methods: PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast. Results: Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk. Conclusion: This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials

Keeping kids safe for active travel to school: A mixed method examination of school policies and practices and children's school travel behaviour.

Active school travel contributes to children's physical, mental and social wellbeing. The prevalence of children's active school travel, however, has been declining in many developed countries. Gaining insights into school culture and environments in relation to school travel behaviour is crucial to inform interventions. Using a multiphase mixed methods approach, this study aimed to provide a comprehensive understanding of how school policies and practices supported or inhibited school travel behaviour in Auckland, New Zealand. Data were drawn from Neighbourhoods for Active Kids, a cross-sectional study of 1085 children aged 8-13 years between February 2015 and December 2016. School representatives were interviewed regarding their policies and practices related to school travel behaviour and traffic around school, and the data were analysed thematically. An overarching theme, sub-themes and categories were contextualised for quantitative modelling using objectively measured school variables (school socioeconomic status, active school travel programme, built environments around school). Mixed effects multinomial logistic regression models were employed to determine associations between school travel mode and objectively measured child (sociodemographic characteristics, traffic safety perceptions) and school variables. Safety was the core concept of school travel policies, procedures and programmes. Significant differences in child variables, school socioeconomic status, and cycle lanes and traffic lights around school were found between children who actively travelled or used public transport to school and those driven to school. Overall, this study demonstrated the important role of school policy and procedures and the potential application of an intersectoral approach for interventions to support changes in school travel behaviour.This work was supported by the Health Research Council of New Zealand [grant number 14/436]; and the Medical Research Council [MC_UU_12015/7]. The work was undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which was funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust. Melody Smith was supported by a Health Research Council of New Zealand Sir Charles Hercus Research Fellowship [17/013]. Suzanne Mavoa was supported by an Australian National Health and Medical Research Council Early Career Fellowship [No. 1121035]

Incidence trends of ductal carcinoma in situ in New Zealand women between 1999 and 2022

Background: In New Zealand, BreastScreen Aotearoa (BSA), a biennial national breast screening programme, was implemented in 1998. This study examines the incidence trends of ductal carcinoma in situ (DCIS) in New Zealand women from 1999 to 2022. Methods: All women with a primary diagnosis of DCIS over the 24-year study period were identified from the New Zealand Cancer Registry and BSA records. Age-standardised incidence rates (ASIR), detection rates (ASDR) and average annual percent changes were calculated. Results: The annual ASIR was 13.5 per 100,000 New Zealand women, and increased by 0.91% (95% confidence interval (CI): 0.26%, 1.66%) annually. Among women aged 45–69 years during 2006–2022, the annual ASIR was 36.3 for programme-detected DCIS, increasing 1.29% (95%CI: 0.13%, 2.73%) per year, and 14.2 for non-programme-detected DCIS, with no significant changes over the study period. The programme-detected ASIRs were highest for Pacific (38.6), Asian (38.2), and Māori (38.0) women. The programme ASDR was 0.55 per 1000 women screened, with no significant changes over time, and was highest for Asian (0.69), and Māori and Pacific (both at 0.65) women. Conclusion: DCIS incidence increased in New Zealand women from 1999 to 2022, driven by an increase in screening participation, and varied by ethnicity

Interaction Between Allelic Variations in Vitamin D Receptor and Retinoid X Receptor Genes on Metabolic Traits

Low vitamin D status has been shown to be a risk factor for several metabolic traits such as obesity, diabetes and cardiovascular disease. The biological actions of 1, 25-dihydroxyvitamin D, are mediated through the vitamin D receptor (VDR), which heterodimerizes with retinoid X receptor, gamma (RXRG). Hence, we examined the potential interactions between the tagging polymorphisms in the VDR (22 tag SNPs) and RXRG (23 tag SNPs) genes on metabolic outcomes such as body mass index, waist circumference, waist-hip ratio (WHR), high- and low-density lipoprotein (LDL) cholesterols, serum triglycerides, systolic and diastolic blood pressures and glycated haemoglobin in the 1958 British Birth Cohort (1958BC, up to n = 5,231). We used Multifactor- dimensionality reduction (MDR) program as a non-parametric test to examine for potential interactions between the VDR and RXRG gene polymorphisms in the 1958BC. We used the data from Northern Finland Birth Cohort 1966 (NFBC66, up to n = 5,316) and Twins UK (up to n = 3,943) to replicate our initial findings from 1958BC

Quantifying Reliable Walking Activity with a Wearable Device in Aged Residential Care: How Many Days Are Enough?

Strong associations exist between quality of life and physical activity for those living in aged residential care (ARC). Suitable and reliable tools are required to quantify physical activity for descriptive and evaluative purposes. We calculated the number of days required for reliable walking outcomes indicative of physical activity in an ARC population using a trunk-worn device. ARC participants (n = 257) wore the device for up to 7 days. Reasons for data loss were also recorded. The volume, pattern, and variability of walking was calculated. For 197 participants who wore the device for at least 3 days, linear mixed models determined the impact of week structure and number of days required to achieve reliable outcomes, collectively and then stratified by care level. The average days recorded by the wearable device was 5.2 days. Day of the week did not impact walking activity. Depending on the outcome and level of care, 2–5 days was sufficient for reliable estimates. This study provides informative evidence for future studies aiming to use a wearable device located on the trunk to quantify physical activity walking out in the ARC population

Comparison of Percentile Tables and Algorithm-Based Calculators for Classification of Blood Pressures in Children and Adolescents with Obesity: A Secondary Analysis of a Clinical Trial

AIM: Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in a cohort of children affected by obesity using tables versus digital calculations in two sets of guidelines. METHODS: This study was a secondary analysis of data collected from a randomised clinical trial of a multidisciplinary life-style assessment and intervention program. Baseline data from 237 children with a body mass index \u3e99th percentile or \u3e91st percentile with weight-related comorbidities and available BP measurements were analysed. We assessed agreement between tables and algorithms in classification of elevated BP/pre-hypertension and hypertension based on the American Academy of Paediatrics (AAP) clinical practice guidelines (CPG) and the older Fourth Report using Cohen\u27s weighted kappa. The prevalence of hypertensive diagnoses was also compared between the two guidelines. RESULTS: Agreement between BP tables and algorithmic calculation of percentiles was discordant, though improved in the AAP CPG compared to the Fourth Report (Cohen\u27s kappa = 0.70 vs. 0.57, respectively). None (0%) were missed diagnoses, and 59 (24.9%) were false positives for the Fourth Report, and 0 (0%) were missed diagnoses, and 49 (20.9%) were false positives for the AAP CPG. Under the recent guidelines, there was an increase in prevalence of 6.0% (95% confidence interval (CI) 2.5-9.4%; P = 0.0001) for BP ≥90th percentile, and of 3.0% (95% CI 0.4-5.6%; p = 0.016) for hypertension (BP ≥ 95th percentile) in the cohort (18.0% and 6.8%, respectively, increased from 12.0% and 3.8%). CONCLUSIONS: Digital calculators over tables in clinical practice are recommended where possible to improve the accuracy of paediatric BP classification. Substantial rates of elevated BP/Hypertension were found in this cohort of children and adolescents with overweight and obesity

Children's Transport Built Environments: A Mixed Methods Study of Associations between Perceived and Objective Measures and Relationships with Parent Licence for Independent Mobility in Auckland, New Zealand.

Children's independent mobility is declining internationally. Parents are the gatekeepers of children's independent mobility. This mixed methods study investigates whether parent perceptions of the neighbourhood environment align with objective measures of the neighbourhood built environment, and how perceived and objective measures relate to parental licence for children's independent mobility. Parents participating in the Neighbourhood for Active Kids study (n = 940) answered an open-ended question about what would make their neighbourhoods better for their child's independent mobility, and reported household and child demographics. Objective measures of the neighbourhood built environment were generated using geographic information systems. Content analysis was used to classify and group parent-reported changes required to improve their neigbourhood. Parent-reported needs were then compared with objective neighbourhood built environment measures. Linear mixed modelling examined associations between parental licence for independent mobility and (1) parent neighbourhood perceptions; and (2) objectively assessed neighbourhood built environment features. Parents identified the need for safer traffic environments. No significant differences in parent reported needs were found by objectively assessed characteristics. Differences in odds of reporting needs were observed for a range of socio-demographic characteristics. Parental licence for independent mobility was only associated with a need for safer places to cycle (positive) and objectively assessed cycling infrastructure (negative) in adjusted models. Overall, the study findings indicate the importance of safer traffic environments for children's independent mobility

Evaluating the effects of an exercise program (Staying UpRight) for older adults in long-term care on rates of falls: study protocol for a randomised controlled trial

Background: Falls are two to four times more frequent amongst older adults living in long-term care (LTC) than community-dwelling older adults and have deleterious consequences. It is hypothesised that a progressive exercise program targeting balance and strength will reduce fall rates when compared to a seated exercise program and do so cost effectively. Methods/design: This is a single blind, parallel-group, randomised controlled trial with blinded assessment of outcome and intention-to-treat analysis. LTC residents (age ≥ 65 years) will be recruited from LTC facilities in New Zealand. Participants (n = 528 total, with a 1:1 allocation ratio) will be randomly assigned to either a novel exercise program (Staying UpRight), comprising strength and balance exercises designed specifically for LTC and acceptable to people with dementia (intervention group), or a seated exercise program (control group). The intervention and control group classes will be delivered for 1 h twice weekly over 1 year. The primary outcome is rate of falls (per 1000 person years) within the intervention period. Secondary outcomes will be risk of falling (the proportion of fallers per group), fall rate relative to activity exposure, hospitalisation for fall-related injury, change in gait variability, volume and patterns of ambulatory activity and change in physical performance assessed at baseline and after 6 and 12 months. Cost-effectiveness will be examined using intervention and health service costs. The trial commenced recruitment on 30 November 2018. Discussion: This study evaluates the efficacy and cost-effectiveness of a progressive strength and balance exercise program for aged care residents to reduce falls. The outcomes will aid development of evidenced-based exercise programmes for this vulnerable population. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12618001827224. Registered on 9 November 2018. Universal trial number U1111-1217-7148