Investigating the impact of developmental coordination difficulties across home, school, and community settings: Findings from the Australian Impact for DCD survey.

AIM: To evaluate the participation difficulties experienced by children with developmental coordination disorder (DCD) in home, school, and community environments. METHODS: The Impact for DCD survey was completed by primary caregivers of 4-18-year-old children with DCD (or synonymous diagnosis) (n = 429). OUTCOMES AND RESULTS: The greatest participation difficulties experienced at home included dressing, eating with utensils, self-care tasks and drawing/writing reported by over 70% of families. At school, fine motor difficulties were also frequently reported, with additional difficulties keeping up or completing tasks, and not feeling supported at school. Socialisation challenges and bullying were also commonly reported (34.9%). As a result of participation difficulties at school, 5.4% were home schooled. Many children engaged in community activity, with 72.0% currently engaged in at least one organised sports-based activity. CONCLUSIONS AND IMPLICATIONS: Increased recognition of the widespread impact of DCD in a child's life is crucial at an individual and societal level. Parents reported their children experiencing significant participation restrictions and difficulties. The findings of this large-scale study have revealed that most children with DCD are not receiving the support they need to thrive, especially at school. This largely reflects a lack of understanding and recognition of the condition and its associated challenges.

Psychosocial wellbeing, parental concerns, and familial impact of children with developmental coordination disorder.

BACKGROUND: Developmental Coordination Disorder (DCD) is a neurodevelopmental condition impacting motor skill acquisition and competence. While previous studies have identified adverse psychosocial outcomes in DCD, they are limited by small or population-screened, community-based samples. AIMS: To understand the psychosocial difficulties, parental concerns, and familial impacts of childhood DCD in a large population-based sample. METHODS AND PROCEDURES: Parents of 310 children aged 4 - 18 years with a diagnosis of DCD (or synonymous term) completed the Impact for DCD survey. Parent-rated measures of emotional problems, peer problems, and prosocial behaviour were compared to normative data. Parental concerns for the impact of DCD on participation, interaction, emotional well-being, and the family system were examined. OUTCOMES AND RESULTS: Compared to typically developing children, children with DCD were rated significantly higher for emotional and peer problems, and significantly lower for prosocial behaviours. Parents most commonly reported concerns for their child's future and withdrawal from physical activity. The presence of one or more co-occurring disorders did not significantly influence outcomes. CONCLUSION AND IMPLICATIONS: Findings highlight the poor psychosocial outcomes for children with DCD. Crucially, poor psychosocial outcomes were just as likely in those with a single diagnosis of DCD as those with DCD and multiple co-occurring diagnoses. Parents reported concerns for their child (i.e., non-participation and social withdrawal) that are not targeted in existing DCD intervention modalities and emphasised the impact of DCD on the whole family unit. WHAT THIS PAPER ADDS: This paper presents data from the largest parent-reported survey of children with a known diagnosis of DCD (or synonymous labels). It highlights the significant impact of DCD on psychosocial outcomes in children across age groups. The children in this study were rated by their parents to have significantly higher levels of emotional and peer problems, and lower prosocial behaviours, than similarly aged Australian children without DCD. It also challenges the misconception that poor psychosocial outcomes in DCD are the result of co-occurring disorders, with outcomes observed to be as poor in children with a sole diagnosis of DCD in this sample. Furthermore, findings highlighted the significant worry and concern that parents with DCD face, particularly around their child's participation and their emotional health. Finally, parents reported on the considerable impact that DCD had on their family unit, regularly causing worry and concern, influencing their choice of activities, and causing financial strain. These concerns and impacts are not addressed in current intervention models for DCD and highlight the need for support mechanisms moving forward.

Reliability of the Commonly Used and Newly-Developed Autism Measures.

PURPOSE: The aim of the present study was to compare scale and conditional reliability derived from item response theory analyses among the most commonly used, as well as several newly developed, observation, interview, and parent-report autism instruments. METHODS: When available, data sets were combined to facilitate large sample evaluation. Scale reliability (internal consistency, average corrected item-total correlations, and model reliability) and conditional reliability estimates were computed for total scores and for measure subscales. RESULTS: Generally good to excellent scale reliability was observed for total scores for all measures, scale reliability was weaker for RRB subscales of the ADOS and ADI-R, reflecting the relatively small number of items for these measures. For diagnostic measures, conditional reliability tended to be very good (> 0.80) in the regions of the latent trait where ASD and non-ASD developmental disability cases would be differentiated. For parent-report scales, conditional reliability of total scores tended to be excellent (> 0.90) across very wide ranges of autism symptom levels, with a few notable exceptions. CONCLUSIONS: These findings support the use of all of the clinical observation, interview, and parent-report autism symptom measures examined, but also suggest specific limitations that warrant consideration when choosing measures for specific clinical or research applications.

Interactions between the lipidome and genetic and environmental factors in autism.

Autism omics research has historically been reductionist and diagnosis centric, with little attention paid to common co-occurring conditions (for example, sleep and feeding disorders) and the complex interplay between molecular profiles and neurodevelopment, genetics, environmental factors and health. Here we explored the plasma lipidome (783 lipid species) in 765 children (485 diagnosed with autism spectrum disorder (ASD)) within the Australian Autism Biobank. We identified lipids associated with ASD diagnosis (n = 8), sleep disturbances (n = 20) and cognitive function (n = 8) and found that long-chain polyunsaturated fatty acids may causally contribute to sleep disturbances mediated by the FADS gene cluster. We explored the interplay of environmental factors with neurodevelopment and the lipidome, finding that sleep disturbances and unhealthy diet have a convergent lipidome profile (with potential mediation by the microbiome) that is also independently associated with poorer adaptive function. In contrast, ASD lipidome differences were accounted for by dietary differences and sleep disturbances. We identified a large chr19p13.2 copy number variant genetic deletion spanning the LDLR gene and two high-confidence ASD genes (ELAVL3 and SMARCA4) in one child with an ASD diagnosis and widespread low-density lipoprotein-related lipidome derangements. Lipidomics captures the complexity of neurodevelopment, as well as the biological effects of conditions that commonly affect quality of life among autistic people.

Profiles of circumscribed interests in autistic youth.

Circumscribed interests (CI) encompass a range of different interests and related behaviors that can be characterized by either a high intensity but otherwise usual topic [referred to as restricted interests (RI)] or by a focus on topics that are not salient outside of autism [referred to as unusual interests (UI)]. Previous research has suggested that there is pronounced variability across individuals in terms of the endorsement of different interests, however, this variability has not been quantified using formal subtyping approaches. Therefore, using Latent Profile Analysis in a sample of 1,892 autistic youth (Mage = 10.82, SDage = 4.14; 420 females), this study aimed to identify subgroups based on the RU and UI profiles. Three profiles of autistic individuals were identified. They were characterized as Low CI, Predominantly RI, and Predominantly UI. Importantly, profiles differed on several key demographic and clinical variables, including age, sex composition, IQ, language level, social and communication abilities, anxiety, and obsessive-compulsive behaviors. Although replication across other samples is needed, the profiles identified in this study are potentially promising for future research given their distinct profiles of RI and UI and unique patterns of associations with key cognitive and clinical variables. Therefore, this study represents an important initial step towards more individualized assessment and support for diverse presentations of CI in autistic youth.

Parent-reported atypical development in the first year of life and age of autism diagnosis.

This study examined whether parent-reported atypical development in their child's first year was associated with age of diagnosis and age when parents first needed to consult a specialist about their child's development. It involved 423 children who participated in the Australian Autism Biobank. Most parents retrospectively identified ≥ 1 domain of atypical child development. Atypical development in most domains was associated with an earlier age when parents felt specialist consultation was needed. Atypical development in the "gaze abnormalities", "lack of response to social stimuli", and "no social communication" subdomains within the social domain was associated with an earlier age of diagnosis, as was atypical development in the "hypo/hypersensitivity" and "preoccupation with parts of objects" subdomains within the stereotyped/restricted behavior domain.

Dental care experiences and clinical phenotypes in children on the autism spectrum.

AIMS: Children diagnosed with autism spectrum disorder may be at higher likelihood of experiencing poorer oral health and difficulties accessing dental health care. However, identifying which children on the autism spectrum may be more vulnerable to experiencing dental care difficulties is still unknown. This study investigated parental reports of oral health and dental service needs of children diagnosed with autism and explored relationships with clinical phenotypes. METHODS AND RESULTS: Participants (n = 140) were parents of children on the autism spectrum who had participated in a large national biobank study, the Australian Autism Biobank, invited to complete additional surveys about oral health, service use, and barriers to care. One third of parents reported their child's oral health was worse than other children the same age, with 26% reporting untreated dental problems. A third of children were reported to have undergone general anaesthesia at least once for dental procedures. Children who had undergone general anaesthesia were more likely to have intellectual disability and greater functional difficulties. Parents of children with greater functional limitations and sensory challenges reported experiencing barriers to accessing dental care more frequently. CONCLUSION: These results have important implications for paediatric dentists working with children diagnosed with autism with co-occurring intellectual, functional, and sensory challenges. Findings may inform the development of more personalised autism-specific supports.

Characterizing restricted and unusual interests in autistic youth.

A broad range of interests characterized by unusual content and/or intensity, labeled as circumscribed interests (CI), are a core diagnostic feature of autism. Recent evidence suggests that a distinction can be drawn between interests that, although characterized by unusually high intensity and/or inflexibility, are otherwise common in terms of their content (e.g., an interest in movies or animals), labeled as restricted interests (RI), and interests that are generally not salient outside of autism (e.g., an interest in traffic lights or categorization), labeled as unusual interests (UI). The current study aimed to further characterize RI and UI by exploring their association with age, sex, IQ, and social motivation, as well as to examine differences in the adaptive benefits and negative impacts of these two subdomains. Parents of 1892 autistic children and adolescents (Mage  = 10.82, SDage  = 4.14; 420 females) completed an online survey including the Dimensional Assessment of Restricted and Repetitive Behaviors and the Social Communication Questionnaire. Both RI and UI were found to be highly frequent. Sex-based differences were observed in the content, but not intensity, of CI such that females were more likely to show interests with a social component. Finally, RI and UI showed distinct patterns of association with age, sex, IQ, and social motivation, as well as metrics of adaptive benefits and negative impacts. Findings afford a more nuanced understanding of sex-based differences in CI and, crucially, provide preliminary evidence that RI and UI represent distinct constructs that should be studied independently in future research.

Understanding the heterogeneity of anxiety in autistic youth: A person-centered approach.

The present study aimed to examine anxiety profiles among children and adolescents on the autism spectrum. It further aimed to characterize the association between the identified anxiety profiles and key clinical and developmental variables. The Spence Children's Anxiety Scale-Parent Version (SCAS-P) data from a large international pooled sample of 870 caregivers of autistic children and adolescents (Mage  = 11.6 years, SDage  = 2.77; 107 females) was used. Latent profile analysis identified a three-anxiety profile solution exhibiting high entropy (0.80) and high latent profile probabilities, with good classification accuracy. Identified profiles fell along the severity spectrum and were named as the mild (n = 498), moderate (n = 272) and severe (n = 100) anxiety profiles. There were no statistically significant differences between the three anxiety profiles in terms of sex distribution. Participants in the mild profile were significantly younger than those in the severe profile, had significantly fewer social communication difficulties than youth in the moderate anxiety profile group and had significantly fewer restricted and repetitive behaviors and lower cognitive functioning scores compared to participants in moderate and severe anxiety profiles. This is the first study to move beyond identifying associations and group-level differences to exploring and identifying characteristics of anxiety-based subgroups at an individual level that differ on key clinical and developmental variables. The subgroups identified in this study are a preliminary, yet important, first step towards informing future assessment and individualized interventions aiming to support young people on the autism spectrum to reduce and manage anxiety. LAY SUMMARY: This study tried to understand if there are subgroups of autistic young people who may have similar anxiety profiles. We found that we could meaningfully group young people into three groups based on how severe the anxiety symptoms their caregivers reported were: a group with low levels of anxiety, those with moderate anxiety, and those with more severe anxiety. We also found that the young people in the mild group were younger, had fewer autism traits and lower levels of intellectual functioning than young people in the other two groups.

An investigation of a novel broad autism phenotype: increased facial masculinity among parents of children on the autism spectrum.

The broad autism phenotype commonly refers to sub-clinical levels of autistic-like behaviour and cognition presented in biological relatives of autistic people. In a recent study, we reported findings suggesting that the broad autism phenotype may also be expressed in facial morphology, specifically increased facial masculinity. Increased facial masculinity has been reported among autistic children, as well as their non-autistic siblings. The present study builds on our previous findings by investigating the presence of increased facial masculinity among non-autistic parents of autistic children. Using a previously established method, a 'facial masculinity score' and several facial distances were calculated for each three-dimensional facial image of 192 parents of autistic children (58 males, 134 females) and 163 age-matched parents of non-autistic children (50 males, 113 females). While controlling for facial area and age, significantly higher masculinity scores and larger (more masculine) facial distances were observed in parents of autistic children relative to the comparison group, with effect sizes ranging from small to medium (0.16 ≤ d ≤ .41), regardless of sex. These findings add to an accumulating evidence base that the broad autism phenotype is expressed in physical characteristics and suggest that both maternal and paternal pathways are implicated in masculinized facial morphology.

The Effects of Using the Sun Safe App on Sun Health Knowledge and Behaviors of Young Teenagers: Results of Pilot Intervention Studies.

BACKGROUND: A balanced approach toward sun exposure and protection is needed by young people. Excessive sun exposure increases their risk for skin cancers such as melanoma, whereas some exposure is necessary for vitamin D and healthy bones. We have developed a new iOS smartphone app-Sun Safe-through a co-design process, which aims to support healthy and balanced decision-making by young teenagers (aged 12-13 years). OBJECTIVE: The aim of this study was to test the capacity of Sun Safe to improve sun health knowledge and behaviors of young teenagers in 3 pilot intervention studies completed in 2020. METHODS: Young teenagers (aged 12-13 years; N=57) were recruited through the web or through a local school via an open-access website and given access to Sun Safe (29/57, 51%) or a placebo (SunDial) app (28/57, 49%). Participants completed sun health questionnaires and knowledge quizzes before and after the 6-week intervention (either on the web or in class) and rated the quality of the app they used via a survey. RESULTS: Of the 57 participants, 51 (89%) participants (26, 51% for placebo arm and 25, 49% for the Sun Safe arm) completed these studies, with most (>50%) reporting that they used a smartphone to access their designated app either "once a fortnight" or "once/twice in total." Improved sun health knowledge-particularly about the UV Index-was observed in participants who were given access to Sun Safe compared with those who used the placebo (-6.2 [percentage correct] difference in predicted means, 95% CI -12.4 to -0.03; P=.049; 2-way ANOVA). Unexpectedly, there were significantly more sunburn events in the Sun Safe group (relative risk 1.7, 95% CI 1.1-1.8; P=.02; Fisher exact test), although no differences in time spent outdoors or sun-protective behaviors were reported. COVID-19 pandemic-related community-wide shutdowns during April 2020 (when schools were closed) reduced the time spent outdoors by >100 minutes per day (-105 minutes per day difference in predicted means, 95% CI -150 to -59 minutes per day; P=.002; paired 2-tailed Student t test). Sun Safe was well-rated by participants, particularly for information (mean 4.2, SD 0.6 out of 5). CONCLUSIONS: Access to the Sun Safe app increased sun health knowledge among young teenagers in these pilot intervention studies. Further investigations with larger sample sizes are required to confirm these observations and further test the effects of Sun Safe on sun-protective behaviors.

Characterising the Early Presentation of Motor Difficulties in Autistic Children.

This study aimed to explore the rates of motor difficulties in children from the Australian Autism Biobank, and how early motor concerns impacted on children functionally. Children with autism aged 2-7 years, including 441 with a Vineland Adaptive Behavior Scale (VABS-II) motor subscale and 385 with a Mullen Scales of Early Learning (MSEL) fine motor subscale were included (n total = 514; 80% male). Approximately 60% of children on the MSEL and ~ 25% on the VABS-II had clinically significant motor impairments. More children with delayed sitting and walking motor milestones had early childhood parent reported motor difficulties (p < 0.001). Early motor delays or concerns may assist identifying individuals who will likely benefit from early ongoing developmental monitoring and early support.

Toward better characterization of restricted and unusual interests in youth with autism.

LAY ABSTRACT: Despite being highly prevalent among people with autism, restricted and unusual interests remain under-researched and poorly understood. This article confirms that restricted interests are very frequent and varied among children and adolescents with autism. It also further extends current knowledge in this area by characterizing the relationship between the presence, number, and type of restricted interests with chronological age, sex, cognitive functioning, and social and communication symptoms.

Autism-related dietary preferences mediate autism-gut microbiome associations.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Developing an Online Tool to Promote Safe Sun Behaviors With Young Teenagers as Co-researchers.

Despite education about the risks of excessive sun exposure, teenagers in Australia are sun-seeking, with sunburn common in summer. Conversely, some regular (time-limited) exposure to sunlight (that avoids sunburn) is necessary for vitamin D and healthy bones and other molecules important for immune and metabolic health. New interventions are thus required to better support teenagers to make healthy and balanced decisions about their sun behaviors. This paper describes the development of a prototype online tool-a smartphone app-that aimed to foster safe sun practices in teenagers. We recruited young adolescents (aged 12-13 years, n = 24) as "co-researchers" to provide ongoing input into the nature and design of the online tool. This age group was selected, as it is a critical time when young people transition from primary education, where "SunSmart" behaviors are entrenched in Australian schools, to high school, where risky behaviors emerge. Through a series of interviews and workshops, we codesigned an Apple iOS smartphone app with the co-researchers, leading health promotion professionals, researchers, and app designers. The developed app, Sun Safe, contains educational content relevant to teenagers about safe sun behaviors, complemented by other features requested by co-researchers and stakeholders to help engage young people, including gamified quizzes to test their sun health knowledge, real-time weather data on the UV Index and temperature, a sunscreen application timer, and reminders to check the UV Index. The developed prototype app was rated well by co-researchers, suggesting it is suitable for further feasibility and efficacy testing as an intervention tool to improve knowledge and promote safe sun behaviors by young adolescents.

Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis.

Importance: Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date. Objective: To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period. Design, Setting, and Participants: This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020. Interventions: Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians. Main Outcomes and Measures: Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05. Results: Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group. Conclusions and Relevance: Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years. Trial Registration: http://anzctr.org.au identifier: ACTRN12616000819426.

Facial asymmetry in parents of children on the autism spectrum.

Greater facial asymmetry has been consistently found in children with autism spectrum disorder (ASD) relative to children without ASD. There is substantial evidence that both facial structure and the recurrence of ASD diagnosis are highly heritable within a nuclear family. Furthermore, sub-clinical levels of autistic-like behavioural characteristics have also been reported in first-degree relatives of individuals with ASD, commonly known as the 'broad autism phenotype'. Therefore, the aim of the current study was to examine whether a broad autism phenotype expresses as facial asymmetry among 192 biological parents of autistic individuals (134 mothers) compared to those of 163 age-matched adults without a family history of ASD (113 females). Using dense surface-modelling techniques on three dimensional facial images, we found evidence for greater facial asymmetry in parents of autistic individuals compared to age-matched adults in the comparison group (p = 0.046, d = 0.21 [0.002, 0.42]). Considering previous findings and the current results, we conclude that facial asymmetry expressed in the facial morphology of autistic children may be related to heritability factors. LAY ABSTRACT: In a previous study, we showed that autistic children presented with greater facial asymmetry than non-autistic children. In the current study, we examined the amount of facial asymmetry shown on three-dimensional facial images of 192 parents of autistic children compared to a control group consisting of 163 similarly aged adults with no known history of autism. Although parents did show greater levels of facial asymmetry than those in the control group, this effect is statistically small. We concluded that the facial asymmetry previously found in autistic children may be related to genetic factors.

Repetitive transcranial magnetic stimulation (rTMS) in autism spectrum disorder: protocol for a multicentre randomised controlled clinical trial.

INTRODUCTION: There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a funded multicentre randomised controlled clinical trial to investigate whether a course of rTMS to the right temporoparietal junction (rTPJ), which has demonstrated abnormal brain activation in ASD, can improve social communication in adolescents and young adults with ASD. METHODS AND ANALYSIS: This study will evaluate the safety and efficacy of a 4-week course of intermittent theta burst stimulation (iTBS, a variant of rTMS) in ASD. Participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (n=150, aged 14-40 years) will receive 20 sessions of either active iTBS (600 pulses) or sham iTBS (in which a sham coil mimics the sensation of iTBS, but no active stimulation is delivered) to the rTPJ. Participants will undergo a range of clinical, cognitive, epi/genetic, and neurophysiological assessments before and at multiple time points up to 6 months after iTBS. Safety will be assessed via a structured questionnaire and adverse event reporting. The study will be conducted from November 2020 to October 2024. ETHICS AND DISSEMINATION: The study was approved by the Human Research Ethics Committee of Monash Health (Melbourne, Australia) under Australia's National Mutual Acceptance scheme. The trial will be conducted according to Good Clinical Practice, and findings will be written up for scholarly publication. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12620000890932).