Longitudinal mediation analysis using natural effect models

Mediation analysis is concerned with the decomposition of the total effect of an exposure on an outcome into the indirect effect, through a given mediator, and the remaining direct effect. This is ideally done using longitudinal measurements of the mediator, which capture the mediator process more finely. However, longitudinal measurements pose challenges for mediation analysis, because the mediators and outcomes measured at a given time point can act as confounders for the association between mediators and outcomes at a later time point; these confounders are themselves affected by the prior exposure and outcome. Such posttreatment confounding cannot be dealt with using standard methods (e.g., generalized estimating equations). Analysis is further complicated by the need for so-called cross-world counterfactuals to decompose the total effect. This work addresses these challenges. In particular, we introduce so-called natural effect models, which parameterize the direct and indirect effect of a baseline exposure with respect to a longitudinal mediator and outcome. These can be viewed as a generalization of marginal structural mean models to enable effect decomposition. We introduce inverse probability weighting techniques for fitting these models, adjusting for (measured) time-varying confounding of the mediator-outcome association. Application of this methodology uses data from the Millennium Cohort Study, a longitudinal study of children born in the United Kingdom between September 2000 and January 2002

Nearest neighbour imputation and variance estimation methods.

In large-scale surveys, non-response is a common phenomenon. This non-response can be of two types; unit and item non-response. In this thesis we deal with item non-response as other responses from the survey unit can be used for adjustment. Usually non-response adjustment is carried out in one of three ways; weighting, imputation and no adjustments. Imputation is the most commonly used adjustment method, either as single imputation or multiple imputations. In this thesis we study single imputation, in particular nearest neighbour methods, and we have developed a new method. Our method is based on dissimilarity measures and is nonparametric and handles categorical and continuous covariates without requiring any transformations. One drawback with this method was that it is relatively computer intensive, so we investigated data reduction methods. For data reduction we developed a new method that uses propensity scores. Propensity score is used as it has properties that suggest that it would make a good method for matching the respondents and non-respondents. We also looked at subset selection of the covariates using graphical modelling and principal component analysis. We found that the data reduction methods gave as good a result as when using all variables and there was considerable reduction in computation time especially with the propensity score method. As the imputed values are not true values, estimating the variance of the parameter of interest using standard methods would underestimate the variance if no allowance is made for the extra uncertainty due to imputed data being used. We examined various existing methods of variance estimation, particularly the bootstrap method, because both nearest neighbour imputation and bootstrap are non parametric. Also bootstrap is a unified method for estimating smooth as well as non-smooth parameters. Shao and Sitter (1996) proposed a bootstrap method, but for some extreme situations this method has problems. We have modified the bootstrap method of Shao and Sitter to overcome this problem and simulations indicate that both methods give good results. The conclusions from the study are that our new method of multivariate nearest neighbour is at least as good as regression based nearest neighbour and is often better. For large data sets, data reduction may be desirable and we recommend our propensity score method as it was observed to be the fastest among the subset selection methods as well as have some other advantages over the others. Imputing using any of the subsets methods we looked at appear to have similar results to imputing using all covariates. To compute the variance of the imputed data, we recommend the method proposed by Shao and Sitter or our modification of Shao and Sitter's method

A dyadic perspective on coping and its effects on relationship quality and psychological distress in couples living with chronic pain : a longitudinal study

Objective Dyadic coping is a process of coping within couples that is intended not only to support the patient with chronic pain but also to maintain equilibrium in the relationship. This study aims to investigate the effect of patient-perceived and spouse-reported dyadic coping on both the patient and their partner's relationship quality and anxiety, stress, and depression over time. Methods One hundred thirty-nine couples, with one partner experiencing chronic pain, participated in this study. Spanning three measurements over six months, couples reported on their anxiety, stress, depression, relationship quality, and dyadic coping. Results Patient-perceived supportive dyadic coping was positively associated with both partners' relationship quality but was negatively associated with spouses' stress over time. Patient-perceived negative dyadic coping was negatively associated with both partners' relationship quality and positively associated with patients' depression and spouses' depression and stress over time. Spouse-reported supportive dyadic coping showed a positive association with their own relationship quality and a negative association with spouses' depression at baseline and patients' depression at three-month follow-up. Spouse-reported negative dyadic coping was negatively associated with their relationship quality at baseline and positively associated with their partner's anxiety and stress at six-month and three-month follow-up, respectively. Similar inference was observed from the findings of growth curve model. Conclusions As compared with spouse report, patient perception of dyadic coping is a better predictor of both partners' relationship quality and psychological outcomes over time. Both partners may benefit from early psychosocial intervention to improve their dyadic coping, relationship quality, and psychological outcomes

Influence of Fear of Pain and Coping Strategies on Health-Related Quality of Life and Patient-Anticipated Outcomes in Patients With Chronic Pain: Cross-Sectional Study Protocol

Background: Fear of pain and coping strategies are emotional-behavioral responses to pain and are known to play an important role in the development and maintenance of pain. It is highly likely that fear of pain and coping strategies influence each other, potentially affecting the course of chronic pain. To our knowledge, the relationship between pain, fear of pain and coping strategies, and how they influence patient-anticipated outcomes and health-related quality of life, have not been investigated. Objective: The aims of this study are to test (1) if both fear of pain and/or coping strategies are sufficient causes for maintaining pain; and (2) whether fear of pain influences coping strategies and pain intensity. The study will also examine the impact of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Methods: The cross-sectional study will be conducted using an online survey. The Fear of Pain Questionnaire-III (FPQ-III), the Brief Coping Inventory (COPE), and EuroQoL-5d (EQ-5D) validated questionnaires will be used to collect data. Information pertaining to demographic factors, pain-related factors, and patient-anticipated outcomes will also be collected. The study has ethics approval from the Human Research Ethics Committee of the University of Adelaide. Study participants will be individuals aged 18 years and above who are experiencing chronic pain (ie, pain lasting more than 6 months). Effect measure modification technique (EMMM) will be used to examine if fear of pain acts as a moderator or mediator between coping strategies and pain. Simple and multinomial logistic regression analysis will be used to examine the effect of fear of pain and coping strategies on health-related quality of life and patient-anticipated outcomes. Results: Recruitment began July 2017 and it is anticipated that data collection will be completed by October 2017. Findings from this study will help to extend our understanding of fear of pain and coping strategies, their interaction, and their impact on health-related quality of life and patient-anticipated outcomes. Conclusions: Fear of pain and coping strategies have significant influence on the experience of chronic pain and its course. This study will help enhance our understanding of the relationship between fear of pain and coping strategies, which may help in developing patient-centered care practices

assessment of pain-related fear in individuals with chronic painful conditions

Background: Heightened fear and anxiety related to pain may result in emotional and behavioral avoidance responses causing disability, distress, and depression. Fear and anxiety associated with pain can potentially change the course of the pain experience. It is plausible that fear and anxiety related to pain affect the duration and frequency of pain experienced by the patient. Aim: The study aimed to examine the applicability of the Fear of Pain Questionnaire-III (FPQ-III) in identifying who are likely to report longer duration and greater frequency of pain experience. Methods: To test this hypothesis, a cross-sectional study was conducted with 579 individuals from a community-based sample living with chronic pain. The factor structure and validity of FPQ-III in the community-based sample were also tested. Results: The findings suggest higher fear of severe pain but lower fear of medical pain, associ- ated with longer duration and more frequent pain experience. The analysis also confirmed the three-factor structure of FPQ-III, demonstrating good internal consistency for fear of severe pain (0.71) and fear of medical pain (0.73) and acceptable range for fear of minor pain (0.65). Conclusion: These findings suggest that the FPQ-III can be potentially applied to identify individuals at risk for prolonged continuous pain and as a screening tool to measure fear and anxiety related to pain

Efficacy of infant simulator programmes to prevent teenage pregnancy: a school-based cluster randomised trial in Western Australia

Background: Infant simulator-based programmes seek to prevent teenage pregnancy. They are utilised in western and developing countries but, despite growing popularity, there is no published evidence of their long-term impact. The aim of this trial was to investigate the effect of such a programme, the Virtual Infant Parenting (VIP) Programme, on the pregnancy outcomes of birth and induced abortion. Methods: Fifty-seven of 66 eligible schools (86%) in Perth, Western Australia enrolled in the pragmatic clustered (by school) randomised trial (ISRCTN24952438) with even randomisation to the intervention and control groups. Between 2003 and 2006, the VIP programme was administered to 1,267 girls in the intervention schools, while 1,567 girls in the control schools received the standard health education curriculum. Participants were aged 13-15 years and were followed until age 20 via data linkage to hospital medical and abortion clinic records. Log binomial and Cox proportional hazards regression was used to test for differences in pregnancy rates between study groups. Findings: Compared to girls Findings: Compared to girls in the control group, a higher proportion of girls in the intervention group recorded at least one birth (7.6%, n=97; 4·3%, n=67) or at least one abortion as the first pregnancy event (8.9%, n=113; 6.4%, n=101). After adjustment for potential confounding, the intervention group had a higher overall pregnancy risk (RR = 1·36, 95% CI 1.10–1·67, p=0.003) compared to the control group. Similar results were obtained using proportional hazard models (HR = 1.35, 95% CI 1.10–1·67, p=0·016). Interpretation: The infant-simulator based VIP Programme did not achieve its aim of reducing teenage pregnancy. Girls in the intervention group were more likely to experience a birth or an induced abortion than those in the control group before turning 20 years of age. Funding: The Health Promotion Research Foundation of Western Australia (Healthway), Lotteries WA, the Western Australian Department of Education and Training and the Western Australian Department of Health

Changes in socioeconomic inequality in Indonesian children's cognitive function from 2000 to 2007: a decomposition analysis

Background: Measuring social inequalities in health is common; however, research examining inequalities in child cognitive function is more limited. We investigated household expenditure-related inequality in children’s cognitive function in Indonesia in 2000 and 2007, the contributors to inequality in both time periods, and changes in the contributors to cognitive function inequalities between the periods. Methods: Data from the 2000 and 2007 round of the Indonesian Family Life Survey (IFLS) were used. Study participants were children aged 7–14 years (n = 6179 and n = 6680 in 2000 and 2007, respectively). The relative concentration index (RCI) was used to measure the magnitude of inequality. Contribution of various contributors to inequality was estimated by decomposing the concentration index in 2000 and 2007. Oaxaca-type decomposition was used to estimate changes in contributors to inequality between 2000 and 2007. Results: Expenditure inequality decreased by 45% from an RCI = 0.29 (95% CI 0.22 to 0.36) in 2000 to 0.16 (95% CI 0.13 to 0.20) in 2007 but the burden of poorer cognitive function was higher among the disadvantaged in both years. The largest contributors to inequality in child cognitive function were inequalities in per capita expenditure, use of improved sanitation and maternal high school attendance. Changes in maternal high school participation (27%), use of improved sanitation (25%) and per capita expenditures (18%) were largely responsible for the decreasing inequality in children’s cognitive function between 2000 and 2007. Conclusions: Government policy to increase basic education coverage for women along with economic growth may have influenced gains in children’s cognitive function and reductions in inequalities in Indonesia.Amelia Maika, Murthy N. Mittinty, Sally Brinkman, Sam Harper, Elan Satriawan, John W. Lync

A preference based measure of complementary feeding quality: Application to the Avon Longitudinal Study of Parents and Children

This paper presents the development of the Complementary Feeding Utility Index (CFUI), a composite index aimed to measure adherence to infant feeding guidelines. Through an axiomatic characterization this paper shows the advantages in using the CFUI are the following: it avoids the use of arbitrary cut-offs, and by converting observed diet preferences into utilities, summing the score is meaningful. In addition, as the CFUI is designed to be scored continuously, it allows the transition from intake of beneficial foods (in low quantities) and intake of detrimental foods (in high quantities) to be more subtle. The paper first describes the rationale being the development of the CFUI and then elaborates on the methodology used to develop the CFUI, including the process of selecting the components. The methodology is applied to data collected from the Avon Longitudinal Study of Parents and Children to show the advantages of the CFUI over traditional diet index approaches. Unlike traditional approaches, the distribution of the CFUI does not peak towards mean value but distributes evenly towards the tails of the distribution.Murthy N. Mittinty, Rebecca K. Golley, Lisa G. Smithers, Laima Brazionis, John W. Lync

Do early life cognitive ability and self-regulation skills explain socio-economic inequalities in academic achievement? An effect decomposition analysis in UK and Australian cohorts

SSocio-economic inequalities in academic achievement emerge early in life and are observed across the globe. Cognitive ability and “non-cognitive” attributes (such as self-regulation) are the focus of many early years’ interventions. Despite this, little research has compared the contributions of early cognitive and self-regulation abilities as separate pathways to inequalities in academic achievement. We examined this in two nationally representative cohorts in the UK (Millennium Cohort Study, n = 11,168; 61% original cohort) and Australia (LSAC, n = 3028; 59% original cohort). An effect decomposition method was used to examine the pathways from socio-economic disadvantage (in infancy) to two academic outcomes: ‘low’ maths and literacy scores (based on bottom quintile) at age 7–9 years. Risk ratios (RRs, and bootstrap 95% confidence intervals) were estimated with binary regression for each pathway of interest: the ‘direct effect’ of socio-economic disadvantage on academic achievement (not acting through self-regulation and cognitive ability in early childhood), and the ‘indirect effects’ of socio-economic disadvantage acting via self-regulation and cognitive ability (separately). Analyses were adjusted for baseline and intermediate confounding. Children from less advantaged families were up to twice as likely to be in the lowest quintile of maths and literacy scores. Around two-thirds of this elevated risk was ‘direct’ and the majority of the remainder was mediated by early cognitive ability and not self-regulation. For example in LSAC: the RR for the direct pathway from socio-economic disadvantage to poor maths scores was 1.46 (95% CI: 1.17–1.79). The indirect effect of socio-economic disadvantage through cognitive ability (RR = 1.13 [1.06–1.22]) was larger than the indirect effect through self-regulation (1.05 [1.01–1.11]). Similar patterns were observed for both outcomes and in both cohorts. Policies to alleviate social inequality (e.g. child poverty reduction) remain important for closing the academic achievement gap. Early interventions to improve cognitive ability (rather than self-regulation) also hold potential for reducing inequalities in children's academic outcomes.Anna Pearce, Alyssa C.P. Sawyer, Catherine R. Chittleborough Murthy N. Mittinty Catherine Law, John W. Lync

Do dietary trajectories between infancy and toddlerhood influence IQ in childhood and adolescence? Results from a prospective birth cohort study

Extent: 9 p.OBJECTIVE: We examined whether trajectories of dietary patterns from 6 to 24 months of age are associated with intelligence quotient (IQ) in childhood and adolescence. METHODS: Participants were children enrolled in a prospective UK birth cohort (n = 7652) who had IQ measured at age 8 and/or 15 years. Dietary patterns were previously extracted from questionnaires when children were aged 6, 15 and 24 months using principal component analysis. Dietary trajectories were generated by combining scores on similar dietary patterns across each age, using multilevel mixed models. Associations between dietary trajectories and IQ were examined in generalized linear models with adjustment for potential confounders. RESULTS: Four dietary pattern trajectories were constructed from 6 to 24 months of age and were named according to foods that made the strongest contribution to trajectory scores; Healthy (characterised by breastfeeding at 6 months, raw fruit and vegetables, cheese and herbs at 15 and 24 months); Discretionary (biscuits, chocolate, crisps at all ages), Traditional (meat, cooked vegetables and puddings at all ages) and, Ready-to-eat (use of ready-prepared baby foods at 6 and 15 months, biscuits, bread and breakfast cereals at 24 months). In fully-adjusted models, a 1 SD change in the Healthy trajectory was weakly associated with higher IQ at age 8 (1.07 (95%CI 0.17, 1.97)) but not 15 years (0.49 (20.28, 1.26)). Associations between the Discretionary and Traditional trajectories with IQ at 8 and 15 years were as follows; Discretionary; 8 years 20.35(21.03, 0.33), 15 years 20.73(21.33, 20.14) Traditional; 8 years 20.19(20.71, 0.33)15 years 20.41(20.77, 20.04)). The Ready-to-eat trajectory had no association with IQ at either age (8 years 0.32(24.31, 4.95), 15 years 1.11(23.10, 5.33). CONCLUSIONS: The Discretionary and Traditional dietary pattern trajectories from 6 to 24 months of age, over the period when food patterns begin to emerge, are weakly associated with IQ in adolescence.Lisa G. Smithers, Rebecca K. Golley, Murthy N. Mittinty, Laima Brazionis, Kate Northstone, Pauline Emmett and John W. Lync