Faculty Bibliography

OBJECTIVE:To further the precision medicine goal of tailoring medical treatment to individual patient characteristics by providing a method of analysis of the effect of test treatment, T, compared to a reference treatment, R, in participants in a RCT who are likely responders to T. METHODS:Likely responders to T are individuals whose expected response at baseline exceeds a prespecified minimum. A prognostic score, the expected response predicted as a function of baseline covariates, is obtained at trial completion. It is a balancing score that can be used to match likely responders randomized to T with those randomized to R; the result is comparable treatment groups that have a common covariance distribution. Treatments are compared based on observed outcomes in this enriched sample. The approach is illustrated in a RCT comparing two treatments for opioid use disorder. RESULTS:A standard statistical analysis of the opioid use disorder RCT found no treatment difference in the total sample. However, a subset of likely responders to T were identified and in this group, T was statistically superior to R. CONCLUSION/CONCLUSIONS:The causal treatment effect of T relative to R among likely responders may be more important than the effect in the whole target population. The prognostic score function provides quantitative information to support patient specific treatment decisions regarding T furthering the goal of precision medicine.

The impact of COVID-19-related stress on perinatal women is of heightened public health concern given the established intergenerational impact of maternal stress-exposure on infants and fetuses. There is urgent need to characterize the coping styles associated with adverse psychosocial outcomes in perinatal women during the COVID-19 pandemic to help mitigate the potential for lasting sequelae on both mothers and infants. This study uses a data-driven approach to identify the patterns of behavioral coping strategies that associate with maternal psychosocial distress during the COVID-19 pandemic in a large multicenter sample of pregnant women (N = 2876) and postpartum women (N = 1536). Data was collected from 9 states across the United States from March to October 2020. Women reported behaviors they were engaging in to manage pandemic-related stress, symptoms of depression, anxiety and global psychological distress, as well as changes in energy levels, sleep quality and stress levels. Using latent profile analysis, we identified four behavioral phenotypes of coping strategies. Critically, phenotypes with high levels of passive coping strategies (increased screen time, social media, and intake of comfort foods) were associated with elevated symptoms of depression, anxiety, and global psychological distress, as well as worsening stress and energy levels, relative to other coping phenotypes. In contrast, phenotypes with high levels of active coping strategies (social support, and self-care) were associated with greater resiliency relative to other phenotypes. The identification of these widespread coping phenotypes reveals novel behavioral patterns associated with risk and resiliency to pandemic-related stress in perinatal women. These findings may contribute to early identification of women at risk for poor long-term outcomes and indicate malleable targets for interventions aimed at mitigating lasting sequelae on women and children during the COVID-19 pandemic.

Prenatal nutrition may significantly impact brain aging. Results from the Dutch Famine Birth Cohort indicated that prenatal undernutrition is negatively associated with cognition, brain volumes, perfusion and structural brain aging in late life, predominantly in men. This study investigates the association between prenatal undernutrition and late-life functional brain network connectivity. In an exploratory resting-state functional magnetic resonance imaging study of 112 participants from the Dutch Famine Birth Cohort, we investigated whether the within- and between-network functional connectivity of the default mode network, salience network and central executive network differ at age 68 in men (N = 49) and women (N = 63) either exposed or unexposed to undernutrition in early gestation. Additionally, we explored sex-specific effects. Compared to unexposed participants, exposed participants revealed multiple clusters of different functional connectivity within and between the three networks studied. Sex-specific analyses suggested a pattern of network desegregation fitting with brain aging in men and a more diffuse pattern of group differences in women. This study demonstrates that associations between prenatal undernutrition and brain network functional connectivity extend late into life.

INTRODUCTION/BACKGROUND:Little is known about how early (eg, commencing antenatally or in the first 12 months after birth) obesity prevention interventions seek to change behaviour and which components are or are not effective. This study aims to (1) characterise early obesity prevention interventions in terms of target behaviours, delivery features and behaviour change techniques (BCTs), (2) explore similarities and differences in BCTs used to target behaviours and (3) explore effectiveness of intervention components in preventing childhood obesity. METHODS AND ANALYSIS/UNASSIGNED:Annual comprehensive systematic searches will be performed in Epub Ahead of Print/MEDLINE, Embase, Cochrane (CENTRAL), CINAHL, PsycINFO, as well as clinical trial registries. Eligible randomised controlled trials of behavioural interventions to prevent childhood obesity commencing antenatally or in the first year after birth will be invited to join the Transforming Obesity in CHILDren Collaboration. Standard ontologies will be used to code target behaviours, delivery features and BCTs in both published and unpublished intervention materials provided by trialists. Narrative syntheses will be performed to summarise intervention components and compare applied BCTs by types of target behaviours. Exploratory analyses will be undertaken to assess effectiveness of intervention components. ETHICS AND DISSEMINATION/UNASSIGNED:The study has been approved by The University of Sydney Human Research Ethics Committee (project no. 2020/273) and Flinders University Social and Behavioural Research Ethics Committee (project no. HREC CIA2133-1). The study's findings will be disseminated through peer-reviewed publications, conference presentations and targeted communication with key stakeholders. PROSPERO REGISTRATION NUMBER/UNASSIGNED:CRD42020177408.

INTRODUCTION/BACKGROUND:Behavioural interventions in early life appear to show some effect in reducing childhood overweight and obesity. However, uncertainty remains regarding their overall effectiveness, and whether effectiveness differs among key subgroups. These evidence gaps have prompted an increase in very early childhood obesity prevention trials worldwide. Combining the individual participant data (IPD) from these trials will enhance statistical power to determine overall effectiveness and enable examination of individual and trial-level subgroups. We present a protocol for a systematic review with IPD meta-analysis to evaluate the effectiveness of obesity prevention interventions commencing antenatally or in the first year after birth, and to explore whether there are differential effects among key subgroups. METHODS AND ANALYSIS/UNASSIGNED:Systematic searches of Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo and trial registries for all ongoing and completed randomised controlled trials evaluating behavioural interventions for the prevention of early childhood obesity have been completed up to March 2021 and will be updated annually to include additional trials. Eligible trialists will be asked to share their IPD; if unavailable, aggregate data will be used where possible. An IPD meta-analysis and a nested prospective meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome will be body mass index z-score at age 24±6 months using WHO Growth Standards, and effect differences will be explored among prespecified individual and trial-level subgroups. Secondary outcomes include other child weight-related measures, infant feeding, dietary intake, physical activity, sedentary behaviours, sleep, parenting measures and adverse events. ETHICS AND DISSEMINATION/UNASSIGNED:Approved by The University of Sydney Human Research Ethics Committee (2020/273) and Flinders University Social and Behavioural Research Ethics Committee (HREC CIA2133-1). Results will be relevant to clinicians, child health services, researchers, policy-makers and families, and will be disseminated via publications, presentations and media releases. PROSPERO REGISTRATION NUMBER/UNASSIGNED:CRD42020177408.

Substance use is increasing throughout Africa, with the prevalence of alcohol, tobacco, cannabis, and other substance use varying regionally. Concurrently, sub-Saharan Africa bears the world's largest HIV burden, with 71% of people living with HIV (PWH) living in Africa. Problematic alcohol, tobacco, and other substance use among PWH is associated with multiple vulnerabilities comprising complex behavioral, physiological, and psychological pathways that include high-risk behaviors (e.g., sexual risk-taking), HIV disease progression, and mental health problems, all of which contribute to nonadherence to antiretroviral therapy. Physiologically, severe substance use disorders are associated with increased levels of biological markers of inflammation; these, in turn, are linked to increased mortality among PWH. The biological mechanisms that underlie the increased risk of substance use among PWH remain unclear. Moreover, the biobehavioral mechanisms by which substance use contributes to adverse health outcomes are understudied in low- and middle-income countries (LMIC). Syndemic approaches to understanding the co-occurrence of substance use and HIV have largely been limited to high-income countries. We propose a syndemic coupling conceptual model to disentangle substance use from vulnerabilities to elucidate underlying disease risk for PWH. This interventionist perspective enables assessment of biobehavioral mechanisms and identifies malleable targets of intervention.

Cancer health disparities remain a significant problem in the USA, compounded by lack of access to care, language barriers and systemic biases in health care. These disparities are particularly evident in areas such as genetics/genomics. For example, Latinas at high risk for hereditary breast and ovarian cancer (HBOC) have extremely low rates of genetic counseling/testing. Long-standing barriers and inequities in access to services such as genetic counseling and testing require innovative solutions. One solution can involve training community outreach and education professionals (CORE-Ps) to bridge the gap between underserved communities and genetic specialists. We sought to develop and pilot test a training program for English-Spanish bilingual CORE-Ps to reduce disparities in access to and uptake of genetic services among Latino populations. Guided by Adult Learning Theory and with input from multiple stakeholders, we developed ÁRBOLES Familiares (Family Trees), an in-person and online training program for bilingual CORE-Ps to facilitate identification, referral, and navigation of Latinas to genetic counseling/testing. We conducted a pilot test of 24 CORE-Ps recruited from across the United States and assessed knowledge, genetic literacy, and self-efficacy at baseline and follow-up. At follow-up, participants in the pilot with complete baseline and follow-up data (N = 15) demonstrated significant improvements in HBOC knowledge, genetic literacy, self-efficacy and reports of fewer barriers to identify/navigate Latinas (ps < .05). Qualitative assessment identified ways to improve the training curriculum. Pilot results suggest ÁRBOLES is a promising approach for training CORE-Ps to identify and refer high-risk Latinas to genetic services. Next steps involve further refinement of ÁRBOLES, development of an online toolkit, and adaptation for virtual delivery.

Cancer and its treatment can precipitate a range of physical and psychological health issues, particularly in old age. Older adult cancer patients have reported experiencing heightened levels of anxiety, depression, and isolation. The current study aims to understand the role of social engagement in influencing older adult cancer patients’ subjective well-being through a Stress and Coping Framework lens. Using National Health and Aging Trends Study data, this research examines frequency of social engagement and its relationship with subjective well-being. Results indicate that greater social engagement improves subjective well-being in older adult cancer patients. Respondents who are unmarried and experiencing greater anxiety and depressive symptoms are at risk of having poor subjective well-being. Efforts to improve subjective well-being in older adults with cancer should consider promoting social engagement. Special attention should be paid to older adult cancer patients who are unmarried or experiencing elevated anxiety or depressive symptoms. Greater research should examine the mechanisms by which social engagement might impact subjective well-being and how this might vary among different racial/ethnic groups.

PURPOSE/OBJECTIVE:AYAs with cancer have unique psychosocial needs, with reproductive health being a primary concern. The ECHO training program provides reproductive health communication training to individuals providing care for AYAs with cancer. The purpose of this project is to describe the growth of ECHO and evaluate changes in learner engagement over a 5-year period. METHODS:ECHO is an 8-week online training program offered annually, with the program including learning modules, discussion topics and reflections, and synchronous discussions. Reflection quality scores and number of words were compared between the 5 cohorts using ANOVA with a p < .05 level of significance. Descriptive statistics summarized module topics, reflections, and synchronous discussions. RESULTS:The average number of reflections per unique learner increased each year (1.4 in cohort 1 vs 4.1 in cohort 5), as did average length and quality of reflections (72.1 words in cohort 1 vs 203.4 words in cohort 5, p < .0001; score of 1.21 in cohort 1 vs 4.46 in cohort 5, p < .0001). The percentage of learners in attendance at synchronous discussions increased between cohorts 4 and 5 (4.8% of learners in cohort 4 vs 18.8% of learners cohort 5). CONCLUSIONS:The ECHO program has seen significant growth and improvement in learner engagement over a 5-year period. This is particularly important given that student learning outcomes in online courses can be predicted by the level of engagement with online content. IMPLICATIONS FOR CANCER SURVIVORS/CONCLUSIONS:As fertility and reproductive health remain a top life goal and discussion priority for AYAs surviving cancer, increasing clinical competencies of AHPs in oncofertility is essential.

Social policies have great potential to improve population health and reduce health disparities. Thus, increasing empirical research seeks to quantify the health effects of social policies by exploiting variation in the timing of policy changes across places. Multiple social policies are often adopted simultaneously or in close succession in the same locations, creating co-occurrence which must be handled analytically for valid inferences. Although this is a substantial methodological challenge for studies aiming to isolate social policy effects, limited prior work has systematically considered analytic solutions within a causal framework or assessed whether these solutions are being adopted. We designated seven analytic solutions to policy co-occurrence, including efforts to disentangle individual policy effects and efforts to estimate the combined effects of co-occurring policies. We leveraged an existing systematic review of social policies and health to evaluate how often policy co-occurrence is identified as a threat to validity and how often each analytic solution is applied in practice. Of the 55 studies, only 17 (31%) reported checking for any co-occurring policies, although 36 (67%) used at least one approach that helps address policy co-occurrence. The most common approaches were: adjusting for measures of co-occurring policies; defining the outcome on subpopulations likely to be affected by the policy of interest (but not other co-occurring policies); and selecting a less-correlated measure of policy exposure. As health research increasingly focuses on policy changes, we must systematically assess policy co-occurrence and apply analytic solutions to strengthen future studies on the health effects of social policies.