Neurofibromatosis 1 (NF1) is a monogenic model for syndromic autism. Statins rescue the social and cognitive phenotype in animal knockout models, but translational trials with subjects > 8 years ...using cognition/behaviour outcomes have shown mixed results. This trial breaks new ground by studying statin effects for the first time in younger children with NF1 and co-morbid autism and by using multiparametric imaging outcomes.
A single-site triple-blind RCT of simvastatin vs. placebo was done. Assessment (baseline and 12-week endpoint) included peripheral MAPK assay, awake magnetic resonance imaging spectroscopy (MRS; GABA and glutamate+glutamine (Glx)), arterial spin labelling (ASL), apparent diffusion coefficient (ADC), resting state functional MRI, and autism behavioural outcomes (Aberrant Behaviour Checklist and Clinical Global Impression).
Thirty subjects had a mean age of 8.1 years (SD 1.8). Simvastatin was well tolerated. The amount of imaging data varied by test. Simvastatin treatment was associated with (i) increased frontal white matter MRS GABA (
(12) = - 2.12,
= .055), GABA/Glx ratio (
(12) = - 2.78,
= .016), and reduced grey nuclei Glx (ANCOVA
< 0.05, Mann-Whitney
< 0.01); (ii) increased ASL perfusion in ventral diencephalon (Mann-Whitney
< 0.01); and (iii) decreased ADC in cingulate gyrus (Mann-Whitney
< 0.01). Machine-learning classification of imaging outcomes achieved 79% (
< .05) accuracy differentiating groups at endpoint against chance level (64%,
= 0.25) at baseline. Three of 12 (25%) simvastatin cases compared to none in placebo met 'clinical responder' criteria for behavioural outcome.
We show feasibility of peripheral MAPK assay and autism symptom measurement, but the study was not powered to test effectiveness. Multiparametric imaging suggests possible simvastatin effects in brain areas previously associated with NF1 pathophysiology and the social brain network.
EU Clinical Trial Register (EudraCT) 2012-005742-38 (www.clinicaltrialsregister.eu).
We investigated the early sociocognitive battery (ESB), a novel measure of preverbal social communication skills, in children with autism participating in the Paediatric Autism Communication ...Trial-Generalised (PACT-G). The associations between ESB scores, language and autism symptoms were assessed in 249 children aged 2–11 years. The results show that ESB subscale scores (social responsiveness, joint attention and symbolic comprehension) were significantly associated with concurrent autism symptoms and receptive and expressive language levels. The pattern of association between the ESB subscale scores differed between the ADOS-2 symptom domains and expressive and receptive language. These findings indicate the potential utility of the ESB as a measure of preverbal social communication in children with autism.
High response rates are essential when questionnaires are used within research, as representativeness can affect the validity of studies and the ability to generalise the findings to a wider ...population. The study aimed to measure the response rate to questionnaires from a large longitudinal epidemiological study and sought to determine if any changes made throughout data collection had a positive impact on the response to questionnaires and addressed any imbalance in response rates by participants' levels of deprivation.
Data were taken from a prospective, comparative study, designed to examine the effects of the reintroduction of water fluoridation on children's oral health over a five-year period. Response rates were analysed for the first year of data collection. During this year changes were made to the questionnaire layout and cover letter to attempt to increase response rates. Additionally a nested randomised control trial compared the effect on response rates of three different reminders to complete questionnaires.
Data were available for 1824 individuals. Sending the complete questionnaire again to non-responders resulted in the highest level of response (25%). A telephone call to participants was the only method that appeared to address the imbalance in deprivation, with a mean difference in deprivation score of 2.65 (95% CI -15.50 to 10.20) between the responders and non-responders.
Initially, low response rates were recorded within this large, longitudinal study giving rise to concerns about non-response bias. Resending the entire questionnaire again was the most effective way of reminding participants to complete the questionnaire. As this is a less labour intensive method than for example, calling participants, more time can then be spent targeting groups who are underrepresented. In order to address these biases, data can be weighted in order to draw conclusions about the population.
Background
Marginalized groups are more likely to experience problems with technology-related access, motivation, and skills. This is known as the “digital divide.” Technology-related exclusion is a ...potential barrier to the equitable implementation of digital health. SlowMo therapy was developed with an inclusive, human-centered design to optimize accessibility and bridge the “digital divide.” SlowMo is an effective, blended digital psychological therapy for paranoia in psychosis.
Objective
This study explores the “digital divide” and mobile app engagement in the SlowMo randomized controlled trial.
Methods
Digital literacy was assessed at baseline, and a multidimensional assessment of engagement (ie, adherence via system analytics and self-report and self-reported user experience) was conducted at 12 weeks after therapy. Engagement was investigated in relation to demographics (ie, gender, age, ethnicity, and paranoia severity).
Results
Digital literacy data demonstrated that technology use and confidence were lower in Black people and older people (n=168). The engagement findings indicated that 80.7% (96/119) of therapy completers met the a priori analytics adherence criteria. However, analytics adherence did not differ by demographics. High rates of user experience were reported overall (overall score: mean 75%, SD 17.1%; n=82). No differences in user experience were found for ethnicity, age, or paranoia severity, although self-reported app use, enjoyment, and usefulness were higher in women than in men.
Conclusions
This study identified technology-related inequalities related to age and ethnicity, which did not influence engagement with SlowMo, suggesting that the therapy design bridged the “digital divide.” Intervention design may moderate the influence of individual differences on engagement. We recommend the adoption of inclusive, human-centered design to reduce the impact of the “digital divide” on therapy outcomes.
Trial Registration
ISRCTN Registry ISRCTN32448671; https://www.isrctn.com/ISRCTN32448671
Interpersonal violence can significantly reduce adolescents' opportunities for becoming happy and healthy adults. Central America is the most violent region in the world and it is estimated that ...adolescents are involved in 82% of all homicides in this region. Family skills training programmes have been designed to prevent interpersonal violence in adolescents. Several studies in high-income countries suggest they are effective. However, there are no published trials assessing effectiveness of these programmes in low- and middle-income countries (LMIC). The aim of this study is to test the effectiveness of the Strengthening Families Programme 10-14 (SFP 10-14 or "Familias Fuertes") in Panama, a LMIC in Central America. An embedded process evaluation will examine the extent to which the intervention is delivered as intended, variation across trial sites, influences on implementation and intervention-context interactions. Cost-effectiveness will also be assessed.
This is a cluster randomised controlled trial. The 28 townships with the highest homicide rates in Panama will be randomly allocated to implementation of SFP 10-14 alongside services-as-usual or to services-as-usual only. Approximately 30 families will be recruited in each township, a total sample of 840 families. Families will be assessed at baseline, approximately eight weeks after baseline (i.e. post intervention), six months and 12 months after. The primary outcome measure will be the parent reported externalising subscale of the Child Behaviour Checklist at T3 (i.e., which is approximately 12 months after baseline). For the process evaluation, recruitment, attendance, fidelity and receipt will be measured. Qualitative interviews with facilitators, trainers, parents and adolescents will explore barriers/facilitators to implementation and intervention receipt. For the cost-effectiveness analysis, service use information will be gathered from parents and adolescents with a three-month recall period. Costs and consequences associated with implementation of the intervention will be identified.
This trial will be the first to evaluate SFP 10-14 in a LMIC. Results have the potential to guide public policies for the prevention of interpersonal violence in Central America and beyond.
ISRCTN Registry, 14023111 . Registered on 13 July 2017.
Approximately 1-2% of mothers may experience severe mental illness (SMI) requiring admission to an inpatient Mother and Baby Unit (MBU). MBUs aim to provide mental health assessment and treatment and ...strengthen the mother-infant relationship, essential for infant development. Whilst MBUs offer various interventions, they do not routinely offer structured parenting interventions. The Baby Triple P Positive Parenting Program (BTP) was developed to enhance parenting competence, psychological coping and the quality of partner and other social support. Guided by lived experience consultation, we aimed to determine the feasibility and acceptability of delivering BTP plus Treatment as Usual (TAU) in this setting.
A multi-site, parallel-group, single-blind pilot randomized controlled trial (registration: ISRCTN12765736) comparing BTP+TAU to TAU in participants, recruited from two MBUs in England. The Baby Triple P intervention consisted of eight parenting sessions, with the final four being delivered over the telephone following MBU discharge. Feasibility outcomes were participant intervention engagement and study retention. Clinical outcomes including maternal parenting competence, bonding and mental health outcomes were assessed at baseline, post-baseline/intervention (10 weeks) and six-month follow-up. Data were analyzed using descriptive statistics and linear regression models. An economic feasibility analysis was also conducted.
Thirty-seven of the 67 eligible participants consented; 34 were randomized (16 to BTP+TAU and 18 to TAU), of whom 20 were retained at post-intervention data collection and 21 at six-month follow-up. Twelve participants (75%) completed the intervention, which was rated as highly acceptable. Clinical outcomes signaled potential improvements in maternal parenting competence, bonding, mood and mental health symptomatology in participants who received the intervention. Healthcare resource use and EQ-5D-5L questionnaires were well-completed by participants. Delivering BTP in this setting is estimated to cost £443-822 per participant.
This is the first trial of a parenting intervention in a MBU setting. BTP is feasible and acceptable to mothers with SMI, with a promising signal for treatment efficacy. Although minor modifications may be required for the collection of observer-rated measures post-MBU discharge, the findings indicate that a larger, definitive trial could be conducted, especially if the setting is extended to include perinatal mental health community settings.
There is growing interest in tailoring psychological interventions for distressing voices and a need for reliable tools to assess phenomenological features which might influence treatment response. ...This study examines the reliability and internal consistency of the Voice Characterisation Checklist (VoCC), a novel 10-item tool which assesses degree of voice characterisation, identified as relevant to a new wave of relational approaches.
The sample comprised participants experiencing distressing voices, recruited at baseline on the AVATAR2 trial between January 2021 and July 2022 (
= 170). Inter-rater reliability (IRR) and internal consistency analyses (Cronbach's alpha) were conducted.
The majority of participants reported some degree of voice personification (94%) with high endorsement of voices as distinct auditory experiences (87%) with basic attributes of gender and age (82%). While most identified a voice intention (75%) and personality (76%), attribution of mental states (35%) to the voice ('What are they thinking?') and a known historical relationship (36%) were less common. The internal consistency of the VoCC was acceptable (10 items, α = 0.71). IRR analysis indicated acceptable to excellent reliability at the item-level for 9/10 items and moderate agreement between raters' global (binary) classification of more vs. less highly characterised voices, κ = 0.549 (95% CI, 0.240-0.859),
< 0.05.
The VoCC is a reliable and internally consistent tool for assessing voice characterisation and will be used to test whether voice characterisation moderates treatment outcome to AVATAR therapy. There is potential wider utility within clinical trials of other relational therapies as well as routine clinical practice.
Previous research has suggested that the way bipolar patients respond to depressive mood impacts on the future course of the illness, with rumination prolonging depression and risk-taking possibly ...triggering hypomania. However, the relationship over time between variables such as mood, self-esteem, and response style to negative affect is complex and has not been directly examined in any previous study--an important limitation, which the present study seeks to address.
In order to maximize ecological validity, individuals diagnosed with bipolar disorder (N = 48) reported mood, self-esteem and response styles to depression, together with contextual information, up to 60 times over a period of six days, using experience sampling diaries. Entries were cued by quasi-random bleeps from digital watches. Longitudinal multilevel models were estimated, with mood and self-esteem as predictors of subsequent response styles. Similar models were then estimated with response styles as predictors of subsequent mood and self-esteem. Cross-sectional associations of daily-life correlates with symptoms were also examined.
Cross-sectionally, symptoms of depression as well as mania were significantly related to low mood and self-esteem, and their increased fluctuations. Longitudinally, low mood significantly predicted rumination, and engaging in rumination dampened mood at the subsequent time point. Furthermore, high positive mood (marginally) instigated high risk-taking, and in turn engaging in risk-taking resulted in increased positive mood. Adaptive coping (i.e. problem-solving and distraction) was found to be an effective coping style in improving mood and self-esteem.
This study is the first to directly test the relevance of response style theory, originally developed to explain unipolar depression, to understand symptom changes in bipolar disorder patients. The findings show that response styles significantly impact on subsequent mood but some of these effects are modulated by current mood state. Theoretical and clinical implications are discussed.
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