The epidemiology, radiology and biological characteristics of interval breast cancers in population mammography screening.

An interval breast cancer is a cancer that emerges following a negative mammographic screen. This overview describes the epidemiology, and the radiological and biological characteristics of interval breast cancers in population mammography screening. Notwithstanding possible differences in ascertainment of interval breast cancers, there was broad variability in reported interval breast cancer rates (range 7.0 to 49.3 per 10,000 screens) reflecting heterogeneity in underlying breast cancer rates, screening rounds (initial or repeat screens), and the length and phase of the inter-screening interval. The majority of studies (based on biennial screening) reported interval breast cancer rates in the range of 8.4 to 21.1 per 10,000 screens spanning the two-year interval with the larger proportion occurring in the second year. Despite methodological limitations inherent in radiological surveillance (retrospective mammographic review) of interval breast cancers, this form of surveillance consistently reveals that the majority of interval cancers represent either true interval or occult cancers that were not visible on the index mammographic screen; approximately 20-25% of interval breast cancers are classified as having been missed (false-negatives). The biological characteristics of interval breast cancers show that they have relatively worse tumour prognostic characteristics and biomarker profile, and also survival outcomes, than screen-detected breast cancers; however, they have similar characteristics and prognosis as breast cancers occurring in non-screened women. There was limited evidence on the effect on interval breast cancer frequency and outcomes following transition from film to digital mammography screening

Overview of tomosynthesis (3D mammography) for breast cancer screening.

This review of the evidence on digital breast tomosynthesis, a 3D-mammography technology, for breast cancer (BC) screening describes two types of studies. Prospective trials comparing tomosynthesis (combined with 2D mammography) with 2D mammography alone in the same participants were based on doublereading practice in mostly biennial screening. These showed incremental BC detection attributed to use of tomosynthesis ranging from 2.2 to 2.7 per 1000 screens. Retrospective studies reported the difference in BC detection between women screened with tomosynthesis (2D plus 3D mammography) or with 2D mammography alone, using single-reading and mostly annual screening. Differences in cancer detection ranged between 0.2 and 2.1 per 1000 screens favoring tomosynthesis. The impact of using tomosynthesis on recall was heterogeneous; however, significant reduction in recall rates was observed among the retrospective studies

Can an incentive-based intervention increase physical activity and reduce sitting among adults? the ACHIEVE (Active Choices IncEntiVE) feasibility study

BackgroundDespite recent interest in the potential of incentivisation as a strategy for motivating healthier behaviors, little remains known about the effectiveness of incentives in promoting physical activity and reducing sedentary behavior, and improving associated health outcomes.This pre-post-test design study investigated the feasibility, appeal and effects of providing non-financial incentives for promoting increased physical activity, reduced sedentary time, and reduced body mass index (BMI) and blood pressure among inactive middle-aged adults.MethodsInactive men (n&thinsp;=&thinsp;36) and women (n&thinsp;=&thinsp;46) aged 40&ndash;65 years were recruited via a not-for-profit insurance fund and participated in a 4 month pre-post design intervention. Baseline and post-intervention data were collected on self-reported physical activity and sitting time (IPAQ-Long), BMI and blood pressure. Participants were encouraged to increase physical activity to 150 mins/week and reduce sedentary behavior by 150 mins/week in progressive increments. Incentives included clothing, recipe books, store gift vouchers, and a chance to win one of four Apple iPad Mini devices. The incentive component of the intervention was supported by an initial motivational interview and text messaging to encourage participants and provide strategies to increase physical activity and reduce sedentary behaviors.ResultsOnly two participants withdrew during the program, demonstrating the feasibility of recruiting and retaining inactive middle-aged participants. While two-thirds of the sample qualified for the easiest physical activity incentive (by demonstrating 100 mins physical activity/week or 100 mins reduced sitting time/week), only one third qualified for the most challenging incentive. Goals to reduce sitting appeared more challenging, with 43% of participants qualifying for the first incentive, but only 20% for the last incentive. More men than women qualified for most incentives. Mean leisure-time physical activity increased by 252 mins/week (leisure-time), with 65% of the sample achieving at least 150 mins/week; and sitting time decreased by 3.1 h/day (both p&thinsp;&lt;&thinsp;0.001) between baseline and follow-up. BMI, systolic and diastolic (men only) blood pressure all significantly decreased. Most participants (50&ndash;85%) reported finding the incentives and other program components helpful/motivating.ConclusionsAcknowledging the uncontrolled design, the large pre-post changes in behavioral and health-related outcomes suggest that the ACHIEVE incentives-based behavior change program represents a promising approach for promoting physical activity and reducing sitting, and should be tested in a randomized controlled trial.<br /

The landscape of COVID-19 trials in Australia

This perspective explores the landscape of COVID-19 trials recruiting in Australia using trial registry data. We identified 56 trials addressing treatment and prevention of COVID-19, and 12 trials addressing indirect effects of the pandemic. Whilst there was substantial innovation in drug development and digital health, the potential of innovation in methodology, such as adaptive trials, remains largely untapped. Data sharing intentions were low, sample sizes were too small to detect differences in clinical outcomes, such as mortality, and lack of core outcome collection precludes evidence synthesis. Infrastructure for innovation would support coordination of research efforts, and reduce research waste

Systematic review and network meta-analysis with individual participant data on cord management at preterm birth (iCOMP): study protocol

Introduction Timing of cord clamping and other cord management strategies may improve outcomes at preterm birth. However, it is unclear whether benefits apply to all preterm subgroups. Previous and current trials compare various policies, including time-based or physiology-based deferred cord clamping, and cord milking. Individual participant data (IPD) enable exploration of different strategies within subgroups. Network meta-analysis (NMA) enables comparison and ranking of all available interventions using a combination of direct and indirect comparisons. Objectives (1) To evaluate the effectiveness of cord management strategies for preterm infants on neonatal mortality and morbidity overall and for different participant characteristics using IPD meta-analysis. (2) To evaluate and rank the effect of different cord management strategies for preterm births on mortality and other key outcomes using NMA. Methods and analysis Systematic searches of Medline, Embase, clinical trial registries, and other sources for all ongoing and completed randomised controlled trials comparing cord management strategies at preterm birth (before 37 weeks’ gestation) have been completed up to 13 February 2019, but will be updated regularly to include additional trials. IPD will be sought for all trials; aggregate summary data will be included where IPD are unavailable. First, deferred clamping and cord milking will be compared with immediate clamping in pairwise IPD meta-analyses. The primary outcome will be death prior to hospital discharge. Effect differences will be explored for prespecified participant subgroups. Second, all identified cord management strategies will be compared and ranked in an IPD NMA for the primary outcome and the key secondary outcomes. Treatment effect differences by participant characteristics will be identified. Inconsistency and heterogeneity will be explored. Ethics and dissemination Ethics approval for this project has been granted by the University of Sydney Human Research Ethics Committee (2018/886). Results will be relevant to clinicians, guideline developers and policy-makers, and will be disseminated via publications, presentations and media releases

Interval breast cancer rates for digital breast tomosynthesis versus digital mammography population screening: An individual participant data meta-analysis

Background: Digital breast tomosynthesis (DBT) improves breast cancer (BC) detection compared to mammography, however, it is unknown whether this reduces interval cancer rate (ICR) at follow-up. Methods: Using individual participant data (IPD) from DBT screening studies (identified via periodic literature searches July 2016 to November 2019) we performed an IPD meta-analysis. We estimated ICR for DBT-screened participants and the difference in pooled ICR for DBT and mammography-only screening, and compared interval BC characteristics. Two-stage meta-analysis (study-specific estimation, pooled synthesis) of ICR included random-effects, adjusting for study and age, and was estimated in age and density subgroups. Comparative screening sensitivity was calculated using screen-detected and interval BC data. Findings: Four prospective DBT studies, from European population-based programs, contributed IPD for 66,451 DBT-screened participants: age-adjusted pooled ICR was 13.17/10,000 (95%CI: 8.25-21.02). Pooled ICR was higher in the high-density (21.08/10,000; 95%CI: 6.71-66.27) than the low-density (8.63/10,000; 95%CI: 5.25-14.192) groups (P = 0.03) however estimates did not differ across age-groups (P = 0.32). Based on two studies that also provided data for 153,800 mammography screens (age-adjusted ICR 17.69/10,000; 95%CI: 13.22-23.66), DBT's pooled ICR was 16.83/10,000 (95%CI: 11.89-23.82). Comparative meta-analysis showed a non-significant difference in ICR (-0.44/10,000; 95%CI: -11.00-10.11) and non-significant difference in screening sensitivity (6.79%; 95%CI: -0.73-14.87%) between DBT and DM but a significant pooled difference in cancer detection rate of 33.49/10,000 (95%CI: 23.88-43.10). Distribution of interval BC prognostic characteristics did not differ between screening modalities except that those occurring in DBT-screened participants were significantly more likely to be negative for axillary-node metastases (P = 0.005). Interpretation: Although heterogeneity in ICR estimates and few datasets limit recommendations, there was no difference between DBT and mammography in pooled ICR despite DBT increasing cancer detection. (C) 2021 The Author(s). Published by Elsevier Ltd

The AEDUCATE Collaboration. Comprehensive antenatal education birth preparation programmes to reduce the rates of caesarean section in nulliparous women. Protocol for an individual participant data prospective meta-analysis

Introduction: Rates of medical interventions in normal labour and birth are increasing. This prospective meta-analysis (PMA) proposes to assess whether the addition of a comprehensive multicomponent birth preparation programme reduces caesarean section (CS) in nulliparous women compared with standard hospital care. Additionally, do participant characteristics, intervention components or hospital characteristics modify the effectiveness of the programme? Methods and analysis: Population: women with singleton vertex pregnancies, no planned caesarean section (CS) or epidural. Intervention: in addition to hospital-based standard care, a comprehensive antenatal education programme that includes multiple components for birth preparation, addressing the three objectives: preparing women and their birth partner/support person for childbirth through education on physiological/hormonal birth (knowledge and understanding); building women’s confidence through psychological preparation (positive mindset) and support their ability to birth without pain relief using evidence-based tools (tools and techniques). The intervention could occur in a hospital-based or community setting. Comparator: standard care alone in hospital-based maternity units. Outcomes: Primary: CS. Secondary: epidural analgesia, mode of birth, perineal trauma, postpartum haemorrhage, newborn resuscitation, psychosocial well-being. Subgroup analysis: parity, model of care, maternal risk status, maternal education, maternal socio-economic status, intervention components. Study design: An individual participant data (IPD) prospective meta-analysis (PMA) of randomised controlled trials, including cluster design. Each trial is conducted independently but share core protocol elements to contribute data to the PMA. Participating trials are deemed eligible for the PMA if their results are not yet known outside their Data Monitoring Committees. Ethics and dissemination: Participants in the individual trials will consent to participation, with respective trials receiving ethical approval by their local Human Research Ethics Committees. Individual datasets remain the property of trialists, and can be published prior to the publication of final PMA results. The overall data for meta-analysis will be held, analysed and published by the collaborative group, led by the Cochrane PMA group. Trial registration number: CRD42020103857

Latest update of the clinical trials landscape in Australia (2006 – 2020)

The latest update of the clinical trials landscape in Australia (2006 – 2020) uses trial registration data to gain an understanding of the clinical trials occurring in Australia. This report is an update of the original report covering 2006-2015 and includes new data from 2016 to 2020. These data are sourced from the Australian New Zealand Clinical Trials Registry (ANZCTR) and US-based ClinicalTrials.gov registry. The purpose of this report is to provide a comprehensive outline of the key characteristics of clinical trials over time. Reporting on clinical trial activity is a crucial step in understanding where improvements may be needed in the clinical trials sector. This report can be used as a reference point when promoting Australian clinical trial activity at national or international forums. It is intended to be used by all those working in or with clinical trials including clinical trial investigators, researchers, funders, industry, policymakers, trial participants and the public. Previous reports analysing trial activity in Australia have helped to identify research gaps and prioritise funding schemes and to inform the design of new national infrastructure that facilitates clinical trial data sharing. We hope this updated report will be of similar use and help to inform the health research agenda in government and industry

Latest update of the clinical trials landscape in Australia (2006 – 2020)

The latest update of the clinical trials landscape in Australia (2006 – 2020) uses trial registration data to gain an understanding of the clinical trials occurring in Australia. This report is an update of the original report covering 2006-2015 and includes new data from 2016 to 2020. These data are sourced from the Australian New Zealand Clinical Trials Registry (ANZCTR) and US-based ClinicalTrials.gov registry. The purpose of this report is to provide a comprehensive outline of the key characteristics of clinical trials over time. Reporting on clinical trial activity is a crucial step in understanding where improvements may be needed in the clinical trials sector. This report can be used as a reference point when promoting Australian clinical trial activity at national or international forums. It is intended to be used by all those working in or with clinical trials including clinical trial investigators, researchers, funders, industry, policymakers, trial participants and the public. Previous reports analysing trial activity in Australia have helped to identify research gaps and prioritise funding schemes and to inform the design of new national infrastructure that facilitates clinical trial data sharing. We hope this updated report will be of similar use and help to inform the health research agenda in government and industry