The Pediatric Autism Research Cohort (PARC) Study: protocol for a patient-oriented prospective study examining trajectories of functioning in children with autism.

INTRODUCTION: The developmentally variable nature of autism poses challenges in providing timely services tailored to a child's needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child's day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the Pediatric Autism Research Cohort (PARC) Study. In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning. METHODS AND ANALYSIS: We aim to recruit 1300 children under 7 years of age with a recent (within 12 months) diagnosis of autism from seven sites: six in Canada; one in Israel. Participants will be followed prospectively from diagnosis to age 8 years, with assessments at 6-month intervals. Parents/caregivers will complete questionnaires administered via a customized online research portal. Following each assessment timepoint, families will receive a research summary report describing their child's progress on adaptive functioning and related domains. Analysis of the longitudinal data will map trajectories and examine child, family and service characteristics associated with chronogeneity (interindividual and intraindividual heterogeneity over time) and possible trajectory turning points around sensitive periods like the transition to school. ETHICS AND DISSEMINATION: Ethics approvals have been received by all sites. All parents/respondents will provide informed consent when enrolling in the study. Using an integrated knowledge translation approach, where stakeholders are directly engaged in the research process, the PARC Study will identify factors associated with trajectories of functioning in children with autism. Resulting evidence will be shared with government policy makers to inform provincial and national programs. Findings will be disseminated at conferences and published in peer-reviewed journals.

Trajectory research in children with an autism diagnosis: A scoping review.

LAY ABSTRACT: The types of outcomes studied in children on the autism spectrum include clinical characteristics, such as social functioning, communication, language, or autism symptoms. Research that measures these outcomes at multiple timepoints is useful to improve our understanding of what to expect as children develop. In trajectory studies, researchers assess outcomes at three or more timepoints. This method has advantages over two-timepoint studies because it allows researchers to describe changes in the speed of development, such as accelerations, plateaus, or slowdowns. We identified and reviewed 103 published trajectory studies in children (to age 18 years) with an autism diagnosis. Importantly, we did not include studies of treatments or their effects, nor did we summarize the results of studies. Instead, this review summarizes the characteristics of the available published research, including the methods used, the many different outcomes that have been studied over time and the ages over which they have been studied. This summary may be of interest to autistic people and caregivers (parents) who want to know about the existence of research that provides answers about what to expect during an autistic child's development. We have recommended that future trajectory research efforts try to make up for the lack of studies from low- and middle-income countries; that more attention is given to the following outcomes that are meaningful to caregivers and autistic people; and to try to fill in the age gaps where more outcome-specific data are needed.

Service access experiences of immigrant and refugee caregivers of autistic children in Canada: A scoping review.

Primary caregivers are the main mediators of care for children with an autism diagnosis in Canada, and the navigation process to gain access to autism-related services is known to be a major burden. These challenges to service access are compounded for newcomers to Canada, which include immigrants and refugees. The purpose of this scoping review is to describe the available research on Canadian newcomer caregiver experiences navigating and accessing autism-related services. After a systematic search and screening process, 28 studies were included. Data were extracted regarding the populations, study aims, and themes reported. Included studies characterized barriers and facilitators to service access and navigation specific to immigrants, while limited information was available for refugees. Based on the existing literature, the authors provide recommendations for possible research approaches, populations to include, and themes to examine in future research to promote health equity in Canadian autism service access.

Knowledge translation strategies for sharing evidence-based health information with older adults and their caregivers: findings from a persona-scenario method.

BACKGROUND: By understanding the information seeking behaviors of older adults, we can better develop or iterate effective information technologies, such as the McMaster Optimal Aging Portal, that provide evidence-based health information to the public. This paper reports health-related information seeking and searching behaviours and provides strategies for effective knowledge translation (KT) to increase awareness and use of reliable health information. METHODS: We conducted a qualitative study with eighteen older adults using the persona-scenario method, whereby participants created personas and scenarios describing older adults seeking health information. Scenarios were analyzed using a two-phase inductive qualitative approach, with the personas as context. From the findings related to pathways of engaging with health information, we identified targeted KT strategies to raise awareness and uptake of evidence-based information resources. RESULTS: Twelve women and six men, 60 to 81 years of age, participated. In pairs, they created twelve personas that captured rural and urban, male and female, and immigrant perspectives. Some scenarios described older adults who did not engage directly with technology, but rather accessed information indirectly through other sources or preferred nondigital modes of delivery. Two major themes regarding KT considerations were identified: connecting to information via other people and personal venues (people included healthcare professionals, librarians, and personal networks; personal venues included clinics, libraries, pharmacies, and community gatherings); and health information delivery formats, (e.g., printed and multimedia formats for web-based resources). For each theme, and any identified subthemes, corresponding sets of suggested KT strategies are presented. CONCLUSIONS: Our findings underline the importance of people, venues, and formats in the actions of older adults seeking trusted health information and highlight the need for enhanced KT strategies to share information across personal and professional networks of older adults. KT strategies that could be employed by organizations or communities sharing evidence-based, reliable health information include combinations of educational outreach and materials, decision support tools, small group sessions, publicity campaigns, champions/opinion leaders, and conferences.

Investigating the Associations Between Child Autistic Symptoms, Socioeconomic Context, and Family Life: A Pilot Study.

Objective: The day-to-day experience of families with an Autistic child may be shaped by both, child characteristics and available resources, which often are influenced by the socioeconomic context of the family. Using a socioecological approach, this study explored the quantitative associations between child autistic symptoms, family socioeconomic status, and family life. Methods: Data came from the Pediatric Autism Research Cohort-PARC Study (pilot). Parents of children with a recent diagnosis of autism completed a set of assessments, including the Autism Family Experience Questionnaire, Autism Impact Measure, and a Sociodemographic Questionnaire. A series of multiple, iterative linear regression models were constructed to ascertain quantitative associations between child autistic symptoms, socioeconomic context, and family life. Results: A total of 50 children (mean age: 76 months; SD: 9.5 months; and 84% male) with data on the variables of interest were included in the analysis. The frequency of child autistic symptoms was associated with family life outcomes (p = 0.02 and R 2 = 24%). Once autistic symptom frequency, symptom impact, and sociodemographic variables were considered, parents of higher educational attainment reported worse family life outcomes compared to their lesser-educated counterparts. This cumulative regression model had considerable explanatory capability (p = 0.01, R 2 = 40%). Conclusion: This study demonstrates the utility of using a socioecological approach to examine the dynamic interplay between child characteristics and family circumstances. Our findings suggest that family life for parents (of an autistic child) who have obtained higher education is reported (by the parents themselves) as less satisfactory compared to that of parents without higher education, once adjusted for the autistic symptom frequency of child, symptom impact, and income. These findings can inform the design and delivery of more family-centered care pathways during the years following a diagnosis of autism.

Coming to understand the child has autism: A process illustrating parents' evolving readiness for engaging in care.

LAY ABSTRACT: What is already known about the topic? Parents of children with autism often learn about their child's autism before diagnosis and can spend long periods seeking care (including assessment) before receiving a diagnosis. Meanwhile, parents' readiness to engage in care at this early stage can vary from parent to parent. What this paper adds? This study revealed how parents come to understand their child has autism-on their own terms, rather than from just talking to professionals. It also explained how parents' growing awareness of their child's autism leads them to feel more motivated to engage in care by seeking information and pursuing services. Four "optional steps" described how parents' growing readiness to engage in care at this early stage can vary, depending on their personal process. Implications for practice, research, or policy The results suggest ways that professionals can be more sensitive (a) to parents' varying awareness of autism and (b) to their varying readiness for being involved in early care. They also suggest ways to tailor parent supports to their individual situation and design care that is more family centered. Not all parents want high levels of involvement. Depending on their personal process, some parents may need care and support that is directed at them before feeling ready for professionals to engage them in care directed at the child.

Using qualitative research perspectives to inform patient engagement in research.

PLAIN ENGLISH SUMMARY: In Canada, and internationally, there is an increased demand for patient engagement in health care research. Patients are being involved throughout the research process in a variety of roles that extend beyond the traditional passive participant role. These practices, referred to collectively as 'patient engagement', have raised questions about how to engage patients in the research process. Specifically, researchers have noted a lack of theory underpinning patient engagement and are looking for guidance on how to select patients and engage patients throughout the research process. In this commentary, we draw on qualitative research perspectives to generate theoretical and methodological ideas that novice or experienced researchers can apply to facilitate patient engagement in research. ABSTRACT: Despite the recent advancements in patient engagement in health care research, there is limited research evidence regarding the best strategies for developing and supporting research partnerships with patients and caregivers. Three particular outstanding concerns that have been reported in the literature and that we will explore in this commentary are: (i) the lack of theoretical underpinning to inform the practice of patient engagement in research; (ii) the lack of knowledge regarding how to select patients to engage in research; and (iii) the lack of clear guidance about the best methods for engaging patients in research. We draw on qualitative research perspectives to reflect on these three areas of concern and propose insights into the theory and methods that we believe are useful for engaging patients in research.

Parent engagement in autism-related care: a qualitative grounded theory study.

Parents of children with autism assume substantial responsibility for navigating intervention to address autism-related concerns, including involvement in therapy. Little is known, from the perspective of these parents, regarding how to best engage and support them in this navigating process as it evolves over the child's development. In this article, we present findings from a large qualitative study that investigated how parents of children with autism navigate intervention, to construct an in-depth theoretical account of how this group comes to be engaged in individual-level care. Using grounded theory methods and a symbolic interactionist framework, we analyzed select documents and 45 intensive interviews conducted with 32 mothers and 9 expert professionals from urban and rural regions of Ontario, Canada. Parent-defined concerns are the central impetus for the core process of navigating intervention, labeled using parents' language making your own way. We describe how this process is analogous to engaging in care. Four meaning-making processes - defining concerns, informing the self, seeing what is involved, and adapting emotionally - all interacting in an ongoing fashion, together account for parents' evolving readiness and motivation for taking action to navigate intervention. We illustrate how parents' readiness and motivation for navigating intervention (and thus for engagement) evolves over a generalized trajectory, according to three highly overlapping processes experienced by most parents: coming to understand their child has autism, going into high gear, and easing off. These findings indicate multiple empirical conditions and factors affecting engagement that service planners and professionals will likely want to consider when seeking parent involvement as a means to improve outcomes in autism. Additionally, theoretical aspects are relevant to the developing understanding of how healthcare consumers in general become engaged in individual care, with implications for patient-centered care.

Reviewing the research methods literature: principles and strategies illustrated by a systematic overview of sampling in qualitative research.

BACKGROUND: Overviews of methods are potentially useful means to increase clarity and enhance collective understanding of specific methods topics that may be characterized by ambiguity, inconsistency, or a lack of comprehensiveness. This type of review represents a distinct literature synthesis method, although to date, its methodology remains relatively undeveloped despite several aspects that demand unique review procedures. The purpose of this paper is to initiate discussion about what a rigorous systematic approach to reviews of methods, referred to here as systematic methods overviews, might look like by providing tentative suggestions for approaching specific challenges likely to be encountered. The guidance offered here was derived from experience conducting a systematic methods overview on the topic of sampling in qualitative research. RESULTS: The guidance is organized into several principles that highlight specific objectives for this type of review given the common challenges that must be overcome to achieve them. Optional strategies for achieving each principle are also proposed, along with discussion of how they were successfully implemented in the overview on sampling. We describe seven paired principles and strategies that address the following aspects: delimiting the initial set of publications to consider, searching beyond standard bibliographic databases, searching without the availability of relevant metadata, selecting publications on purposeful conceptual grounds, defining concepts and other information to abstract iteratively, accounting for inconsistent terminology used to describe specific methods topics, and generating rigorous verifiable analytic interpretations. Since a broad aim in systematic methods overviews is to describe and interpret the relevant literature in qualitative terms, we suggest that iterative decision making at various stages of the review process, and a rigorous qualitative approach to analysis are necessary features of this review type. CONCLUSIONS: We believe that the principles and strategies provided here will be useful to anyone choosing to undertake a systematic methods overview. This paper represents an initial effort to promote high quality critical evaluations of the literature regarding problematic methods topics, which have the potential to promote clearer, shared understandings, and accelerate advances in research methods. Further work is warranted to develop more definitive guidance.

Factors explaining the heterogeneity of effects of patient decision aids on knowledge of outcome probabilities: a systematic review sub-analysis.

BACKGROUND: There is considerable unexplained heterogeneity in previous meta-analyses of randomized controlled trials (RCTs) evaluating the effects of patient decision aids on the accuracy of knowledge of outcome probabilities. The purpose of this review was to explore possible effect modification by three covariates: the type of control intervention, decision aid quality and patients' baseline knowledge of probabilities. METHODS: A sub-analysis of studies previously identified in the 2011 Cochrane review on decision aids for people facing treatment and screening decisions was conducted. Additional unpublished data were requested from relevant study authors to maximize the number of eligible studies. RCTs (to 2009) comparing decision aids with standardized probability information to control interventions (lacking such information) and assessing the accuracy of patient knowledge of outcome probabilities were included. The proportions of patients with accurate knowledge of outcome probabilities in each group were converted into relative effect measures. Intervention quality was assessed using the International Patient Decision Aid Standards instrument (IPDASi) probabilities domain. RESULTS: A main effects analysis of 17 eligible studies confirmed that decision aids significantly improve the accuracy of patient knowledge of outcome probabilities (relative risk = 1.80 [1.51, 2.16]), with considerable heterogeneity (87%). The type of control did not modify effects. Meta-regression suggested that the IPDASi probabilities domain score (reflecting decision aid quality) is a potential effect modifier (P = 0.037), accounting for a quarter of the variability (R² = 0.28). Meta-regression indicated the control event rate (reflecting baseline knowledge) is a significant effect modifier (P = 0.001), with over half the variability in ln(OR) explained by the linear relationship with log-odds for the control group (R² = 0.52); this relationship was slightly strengthened after correcting for the statistical dependence of the effect measure on the control event rate. CONCLUSIONS: Patients' baseline level of knowledge of outcome probabilities is an important variable that explains the heterogeneity of effects of decision aids on improving accuracy of this knowledge. Greater relative effects are observed when the baseline proportion of patients with accurate knowledge is lower. This may indicate that decision aids are more effective in populations with lower knowledge.

Inconsistent definitions for intention-to-treat in relation to missing outcome data: systematic review of the methods literature.

BACKGROUND: Authors of randomized trial reports seem to hold a variety of views regarding the relationship between missing outcome data (MOD) and intention to treat (ITT). The objectives of this study were to systematically investigate how authors of methodology articles define ITT in the presence of MOD, how they recommend handling MOD under ITT, and to make a proposal for potential improvement in the definition and use of ITT in relation to MOD. METHODS AND FINDINGS: We systematically searched MEDLINE in February 2009 for methodological articles written in English that devoted at least one paragraph to ITT and two other paragraphs to either ITT or MOD. We excluded original trial reports, observational studies, and clinical systematic reviews. Working in teams of two, we independently extracted relevant information from each eligible article. Of 1007 titles and abstracts reviewed, 66 articles met eligibility criteria. Five (8%) did not provide a definition of ITT; 25 (38%) mentioned MOD but did not discuss its relationship to ITT; and 36 (55%) discussed the relationship of MOD with ITT. These 36 articles described one or more of three statements: complete follow-up is required for ITT (58%); ITT and MOD are separate issues (17%); and ITT requires a specific strategy for handling MOD (78%); 17 (47%) endorsed more than one relationship. The most frequently mentioned strategies for handling MOD within ITT were: using the last outcome carried forward (50%); sensitivity analysis (50%); and use of available data to impute missing data (46%). CONCLUSION: We found that there is no consensus on the definition of ITT in relation to MOD. For conceptual clarity, we suggest that both reports of randomized trials and systematic reviews separately consider and describe how they deal with participants with complete data and those with MOD.

Activity-dependent synaptic plasticity in the supraoptic nucleus of the rat hypothalamus.

Activity-dependent long-term synaptic changes were investigated at glutamatergic synapses in the supraoptic nucleus (SON) of the rat hypothalamus. In acute hypothalamic slices, high frequency stimulation (HFS) of afferent fibres caused long-term potentiation (LTP) of the amplitude of AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) recorded with the whole-cell patch-clamp technique. LTP was also obtained in response to membrane depolarization paired with mild afferent stimulation. On the other hand, stimulating the inputs at 5 Hz for 3 min at resting membrane potential caused long-term depression (LTD) of excitatory transmission in the SON. These forms of synaptic plasticity required the activation of NMDA receptors since they were abolished in the presence of D-AP5 or ifenprodil, two selective blockers of these receptors. Analysis of paired-pulse facilitation and trial-to-trial variability indicated that LTP and LTD were not associated with changes in the probability of transmitter release, thereby suggesting that the locus of expression of these phenomena was postsynaptic. Using sharp microelectrode recordings in a hypothalamic explant preparation, we found that HFS also generates LTP at functionally defined glutamatergic synapses formed between the organum vasculosum lamina terminalis and SON neurons. Taken together, our findings indicate that glutamatergic synapses in the SON exhibit activity-dependent long-term synaptic changes similar to those prevailing in other brain areas. Such forms of plasticity could play an important role in the context of physiological responses, like dehydration or lactation, where the activity of presynaptic glutamatergic neurons is strongly increased.