A smartphone app effectively facilitates mothers' mind-mindedness: A randomized controlled trial.

The efficacy of a smartphone app intervention (BabyMind©) in facilitating mind-mindedness was investigated in a randomized controlled trial, assigning mothers and their 6-month-olds (N = 152; 72 girls, 146 White) to intervention or active control conditions. Mothers who had received the BabyMind© app intervention scored higher for appropriate (d = .61, 95% CI .28, .94) and lower for non-attuned (d = -.55, 95% CI -.92, -.18) mind-related comments at follow-up (age 12 months), compared with their control group counterparts. Adjusting for missing data did not alter this pattern of findings. Mothers' baseline parental reflective functioning did not moderate these relations. Results are discussed in terms of the benefits of early intervention and exploring the efficacy of the app in more diverse populations.

Is behavioural activation an effective treatment for depression in children and adolescents? An updated systematic review and meta-analysis.

Behavioural Activation (BA)-a brief therapy based on the scheduling of enjoyable, purposeful and rewarding activities-is an effective and cost-effective treatment for depression in adults that shows promise for children and adolescents. We provide an update on a previous systematic review of evidence on BA-delivered in-person, telephone, or online-for depression and comorbid anxiety in children and adolescents. We conducted systematic literature searches in 6 databases up to February 2024. We included all study designs evaluating BA with participants up to 18 years old with diagnosable depression, as established by a validated screening tool or diagnostic manual. We used the Moncrieff Scale and the Cochrane Risk of Bias tool to assess study quality. We summarised the findings of all study types with a narrative synthesis and of randomised controlled trials (RCTs) with a meta-analysis. Overall, 24 studies (6 RCTs, 18 pre-post evaluations, n = 2,758) met our inclusion criteria. A meta-analysis of 4 RCTs (n = 156) showed that BA has a small effect of 0.24 (Hedge's adjusted g) in reducing depression symptoms compared to a waiting-list control, usual care and other therapies. Online and telephone-facilitated BA was shown to be feasible in 3 studies and effective in 1. Outcomes on comorbid anxiety were mixed. No economic evaluations met our inclusion criteria. BA shows sufficient promise as an intervention for reducing depression symptoms in children and adolescents to justify the need for further RCTs, providing that five conditions are met: studies are powered to detect a minimal clinically important difference; BA materials are fit-for-purpose to produce clinically meaningful change; follow-ups are longer than 6 months; primary outcomes are child-reported; and intervention costs, resource use and adverse events are reported.

One session treatment (OST) is equivalent to multi-session cognitive behavioral therapy (CBT) in children with specific phobias (ASPECT): results from a national non-inferiority randomized controlled trial.

BACKGROUND: 5%-10% children and young people (CYP) experience specific phobias that impact daily functioning. Cognitive Behaviour Therapy (CBT) is recommended but has limitations. One Session Treatment (OST), a briefer alternative incorporating CBT principles, has demonstrated efficacy. The Alleviating Specific Phobias Experienced by Children Trial (ASPECT) investigated the non-inferiority of OST compared to multi-session CBT for treating specific phobias in CYP. METHODS: ASPECT was a pragmatic, multi-center, non-inferiority randomized controlled trial in 26 CAMHS sites, three voluntary agency services, and one university-based CYP well-being service. CYP aged 7-16 years with specific phobia were randomized to receive OST or CBT. Clinical non-inferiority and a nested cost-effectiveness evaluation was assessed 6-months post-randomization using the Behavioural Avoidance Task (BAT). Secondary outcome measures included the Anxiety Disorder Interview Schedule, Child Anxiety Impact Scale, Revised Children's Anxiety Depression Scale, goal-based outcome measure, and EQ-5DY and CHU-9D, collected blind at baseline and six-months. RESULTS: 268 CYPs were randomized to OST (n = 134) or CBT (n = 134). Mean BAT scores at 6 months were similar across groups in both intention-to-treat (ITT) and per-protocol (PP) populations (CBT: 7.1 (ITT, n = 76), 7.4 (PP, n = 57), OST: 7.4 (ITT, n = 73), 7.6 (PP, n = 56), on the standardized scale-adjusted mean difference for CBT compared to OST -0.123, 95% CI -0.449 to 0.202 (ITT), mean difference -0.204, 95% CI -0.579 to 0.171 (PP)). These findings were wholly below the standardized non-inferiority limit of 0.4, suggesting that OST is non-inferior to CBT. No between-group differences were found on secondary outcomes. OST marginally decreased mean service use costs and maintained similar mean Quality Adjusted Life Years compared to CBT. CONCLUSIONS: One Session Treatment has similar clinical effectiveness to CBT for specific phobias in CYP and may be a cost-saving alternative.

Cost and effectiveness of one session treatment (OST) for children and young people with specific phobias compared to multi-session cognitive behavioural therapy (CBT): results from a randomised controlled trial.

BACKGROUND: In the UK, around 93,000 (0.8%) children and young people (CYP) are experiencing specific phobias that have a substantial impact on daily life. The current gold-standard treatment-multi-session cognitive behavioural therapy (CBT) - is effective at reducing specific phobia severity; however, CBT is time consuming, requires specialist CBT therapists, and is often at great cost and limited availability. A briefer variant of CBT called one session treatment (OST) has been found to offer similar clinical effectiveness for specific phobia as multi-session CBT. The aim of this study was to assess the cost-effectiveness of OST compared to multi-session CBT for CYP with specific phobias through the Alleviating Specific Phobias Experienced by Children Trial (ASPECT), a two-arm, pragmatic, multi-centre, non-inferiority randomised controlled trial. METHODS: CYP aged seven to 16 years with specific phobias were recruited nationally via Health and Social Care pathways, remotely randomised to the intervention group (OST) or the control group (CBT-based therapies) and analysed (n = 267). Resource use based on NHS and personal social services perspective and quality adjusted life years (QALYs) measured by EQ-5D-Y were collected at baseline and at six-month follow-up. Incremental cost-effectiveness ratio (ICER) was calculated, and non-parametric bootstrapping was conducted to capture the uncertainty around the ICER estimates. The results were presented on a cost-effectiveness acceptability curve (CEAC). A set of sensitivity analyses (including taking a societal perspective) were conducted to assess the robustness of the primary findings. RESULTS: After adjustment and bootstrapping, on average CYP in the OST group incurred less costs (incremental cost was -£302.96 (95% CI -£598.86 to -£28.61)) and maintained similar improvement in QALYs (QALYs gained 0.002 (95% CI - 0.004 to 0.008)). The CEAC shows that the probability of OST being cost-effective was over 95% across all the WTP thresholds. Results of a set of sensitivity analyses were consistent with the primary outcomes. CONCLUSION: Compared to CBT, OST produced a reduction in costs and maintained similar improvement in QALYs. Results from both primary and sensitivity analyses suggested that OST was highly likely to be cost saving. TRIAL REGISTRATION: ISRCTN19883421 (30/11/2016).

Mind-mindedness versus mentalistic interpretations of behavior: Is mind-mindedness a relational construct?

Mind-mindedness is a measure of the tendency to represent significant others in internal state terms and is central to supportive parent-infant relationships. The two studies reported here explored whether mind-mindedness generalizes to representations of unknown individuals, using a novel task that assessed individual differences in adults' tendency to interpret others' behavior with reference to their internal states: the Unknown Mother-Infant Interaction Task (UMIIT). We compared UMIIT performance with measures of mind-mindedness from (a) adults' descriptions of close friends and partners (Study 1, N = 96) and (b) mothers' appropriate versus nonattuned comments on their infants' internal states (Study 2, N = 56). In line with the proposal that mind-mindedness is a relational construct, UMIIT performance was unrelated to mind-mindedness in both studies.

La consciente mentalidad es una medida que tiende a representar a quienes nos son importantes en términos de un estado interno y es esencial para las relaciones de mucho apoyo entre progenitores e infantes. Los dos estudios que se reportan aquí exploraron si la mentalidad consciente generaliza al punto de representar a individuos desconocidos, usando una novedosa tarea que evalúa las diferencias individuales en la tendencia de los adultos a interpretar la conducta de otros en función de sus estados mentales: El Trabajo de la Interacción Madre Desconocida-Infante (UMIIT). Comparamos la actuación de UMIIT con las medidas de mentalidad consciente de (a) descripciones de adultos sobre amigos cercanos y parejas (Estudio 1, N = 96), y (b) los comentarios apropiados de las madres versus sus no armonizados comentarios con respecto a los estados internos de sus infantes (Estudio 2, N = 56). Alineado con la propuesta de que la mentalidad consciente es un concepto de la relación, la actuación de UMIIT no estuvo relacionada con la mentalidad consciente en ninguno de los estudios.

L'esprit-qualité mentale (en anglais mind-mindedness) est une mesure de la tendance à représenter les personnes qui nous sont chères en des termes d'état interne. Elle est centrale aux relations parent-enfant positives. Les deux études dont on fait état ici ont exploré si l'esprit-qualité mentale généralise les représentations d'individus inconnus, en utilisant une tâche nouvelle qui a évalué les différences individuelles dans la tendance des adultes à interpréter le comportement des autres en référence à leurs états internes: la Tâche de Mère Inconnue-Interaction du Nourrisson (UMIIT en anglais, soit Unknown Mother-Infant Interaction Task). Nous avons comparé la performance UMIIT aux mesures de l'esprit-qualité mentale de (a) descriptions d'adultes de leurs amis proches et de leurs partenaires (Etude 1, N = 96) et (b) de commentaires appropriés par rapport à pas trop appropriés des mères sur les états internes de leurs nourrissons (Etude 2, N = 56). Conformément à la proposition selon laquelle l'esprit-qualité mentale est une construction relationnelle, la performance de l'UMIIT n'était pas liée à l'esprit-qualité mentale dans les deux études.

Relationship between cognitive functioning, mood, and other patient factors on quality of life in metastatic brain cancer.

OBJECTIVE: Neurocognitive functioning (NCF), mood disturbances, physical functioning, and social support all share a relationship with health-related quality of life (HRQOL). However, investigations into these relationships have not been conducted in persons with brain metastases (BM). PATIENTS AND METHODS: Ninety-three newly diagnosed persons with BM were administered various cognitive batteries. Data were collected across a wide range of categories (ie, cognitive, demographic, disease/treatment, mood, social support, physical functioning). The Functional Assessment of Cancer Treatment (FACT) scale was used to measure HRQOL. RESULTS: Mood and physical function correlated with lower HRQOL in every measured domain. Verbal learning and memory correlated with every FACT subscale except emotional quality of life. Social support also correlated with several HRQOL domains. Stepwise linear regression revealed that mood predicted general well-being and several FACT subscales, including physical, emotional and cognitive well-being. Social support and physical health were predictive of general well-being. Verbal learning and memory predicted cognitive well-being. CONCLUSION: HRQOL is a complex construct affected by numerous variables. In particular, mood, physical functioning, and learning and memory were important predictors of HRQOL, and clinicians are encouraged to obtain information in these areas during baseline assessments in persons with BM.

Chiral versus achiral crystal structures of 4-benzyl-1H-pyrazole and its 3,5-di-amino derivative.

The crystal structures of 4-benzyl-1H-pyrazole (C10H10N2, 1) and 3,5-di-amino-4-benzyl-1H-pyrazole (C10H12N4, 2) were measured at 150 K. Although its different conformers and atropenanti-omers easily inter-convert in solution by annular tautomerism and/or rotation of the benzyl substituent around the C(pyrazole)-C(CH2) single bond (as revealed by 1H NMR spectroscopy), 1 crystallizes in the non-centrosymmetric space group P21. Within its crystal structure, the pyrazole and phenyl aromatic moieties are organized into alternating bilayers. Both pyrazole and phenyl layers consist of aromatic rings stacked into columns in two orthogonal directions. Within the pyrazole layer, the pyrazole rings form parallel catemers by N-H⋯N hydrogen bonding. Compound 2 adopts a similar bilayer structure, albeit in the centrosymmetric space group P21/c, with pyrazole N-H protons as donors in N-H⋯π hydrogen bonds with neighboring pyrazole rings, and NH2 protons as donors in N-H⋯N hydrogen bonds with adjacent pyrazoles and other NH2 moieties. The crystal structures and supra-molecular features of 1 and 2 are contrasted with the two known structures of their analogs, 3,5-dimethyl-4-benzyl-1H-pyrazole and 3,5-diphenyl-4-benzyl-1H-pyrazole.

Adapting and validating the Autism Diagnostic Interview - Revised for use with deaf children and young people.

LAY ABSTRACT: Autism assessment processes need to improve for deaf children as they are currently being diagnosed later than their hearing counterparts and misdiagnosis can occur. We took one of the most commonly used parent developmental interviews for autism spectrum disorder the Autism Diagnostic Interview-Revised and adapted it using international expert advice. Modifications were proposed and agreed by the expert panel for 45% of items; the remaining 55% of items were unchanged. We then tested the revised version, adapted for deaf children (Autism Diagnostic Interview-Revised Deaf Adaptation), in a UK sample of 78 parents/carers of deaf children with autism spectrum disorder and 126 parents/carers with deaf children without autism spectrum disorder. When compared to National Institute for Health and Care Excellence guideline standard clinical assessments, the Autism Diagnostic Interview-Revised Deaf Adaptation diagnostic algorithm threshold scores could identify those deaf children with a definite diagnosis (true autism spectrum disorder positives) well (sensitivity of 89% (79%-96%)) and those deaf children who did not have autism spectrum disorder (true autism spectrum disorder negatives) well (specificity of 81% (70%-89%)). Our findings indicate that the Autism Diagnostic Interview-Revised Deaf Adaptation is likely to prove a useful measure for the assessment of deaf children with suspected autism spectrum disorder and that further research would be helpful.

One-session treatment for specific phobias: Barriers, facilitators and acceptability as perceived by children & young people, parents, and clinicians.

Between 2015 and 2020 the Alleviating Specific Phobias Experienced by Children Trial (ASPECT) was conducted in the UK to examine the non-inferiority of One-Session Treatment in comparison to Cognitive Behavioural Therapy based interventions for children and young people with specific phobias. A nested qualitative evaluation was conducted as part of this trial to examine the acceptability of One-Session Treatment. Qualitative interviews were conducted with children and young people taking part in the trial, their parents/guardians, and clinicians delivering the intervention, about their experiences and the acceptability of One Session Treatment. Interviews were digitally recorded and transcribed verbatim. Analysis followed a qualitative framework approach, a widely used method of analysing primary qualitative data pertaining to healthcare practices with policy relevance. Stakeholder groups found One Session Treatment to be an acceptable intervention and barriers and facilitators for its implementation into services were also identified. Potential barriers included challenges to patient flow and treatment scepticism, whilst facilitators included adopting a child-centred approach, child readiness and suitability, opportunity for increased momentum, parental support and involvement, and proximal and distal gains. For One Session Treatment's successful implementation into services, consideration of these barriers is needed and suitability guidance for its use in this population should be developed. Further research exploring children and young people's experiences of receiving Cognitive Behavioural Therapy and its acceptability in comparison to One Session Treatment would be welcomed.

Adapting and validating the Autism Diagnostic Observation Schedule Version 2 for use with deaf children and young people.

We report a Delphi Consensus modification and first validation study of the Autism Diagnostic Observation Schedule - 2 with deaf children and young people (ADOS-2 Deaf adaptation). Validation included 122 deaf participants (aged 2-18 years), 63 with an Autism Spectrum Disorder (ASD). This was compared to a National Institute for Health and Clinical Excellence (NICE) guideline standard clinical assessment by blinded independent specialist clinicians. Results showed overall sensitivity 73% (95%CI 60%, 83%); specificity 71% (95%CI 58%, 82%), and for the more common modules 1-3 (combined as in previous studies) sensitivity 79% (95% CI 65-89%); specificity 79% (95% CI 66-89%) suggesting this instrument will be a helpful addition for use with deaf children and young people.

One-session treatment compared with multisession CBT in children aged 7-16 years with specific phobias: the ASPECT non-inferiority RCT.

BACKGROUND: Up to 10% of children and young people have a specific phobia that can significantly affect their mental health, development and daily functioning. Cognitive-behavioural therapy-based interventions remain the dominant treatment, but limitations to their provision warrant investigation into low-intensity alternatives. One-session treatment is one such alternative that shares cognitive-behavioural therapy principles but has a shorter treatment period. OBJECTIVE: This research investigated the non-inferiority of one-session treatment to cognitive-behavioural therapy for treating specific phobias in children and young people. The acceptability and cost-effectiveness of one-session treatment were examined. DESIGN: A pragmatic, multicentre, non-inferiority randomised controlled trial, with embedded economic and qualitative evaluations. SETTINGS: There were 26 sites, including 12 NHS trusts. PARTICIPANTS: Participants were aged 7-16 years and had a specific phobia defined in accordance with established international clinical criteria. INTERVENTIONS: Participants were randomised 1 : 1 to receive one-session treatment or usual-care cognitive-behavioural therapy, and were stratified according to age and phobia severity. Outcome assessors remained blind to treatment allocation. MAIN OUTCOME MEASURES: The primary outcome measure was the Behavioural Avoidance Task at 6 months' follow-up. Secondary outcomes included the Anxiety Disorder Interview Schedule, Child Anxiety Impact Scale, Revised Children's Anxiety and Depression Scale, a goal-based outcome measure, Child Health Utility 9D, EuroQol-5 Dimensions Youth version and resource usage. Treatment fidelity was assessed using the Cognitive Behaviour Therapy Scale for Children and Young People and the One-Session Treatment Rating Scale. RESULTS: A total of 274 participants were recruited, with 268 participants randomised to one-session treatment (n = 134) or cognitive-behavioural therapy (n = 134). A total of 197 participants contributed some data, with 149 participants in the intention-to-treat analysis and 113 in the per-protocol analysis. Mean Behavioural Avoidance Task scores at 6 months were similar across treatment groups when both intention-to-treat and per-protocol analyses were applied [cognitive-behavioural therapy: 7.1 (intention to treat), 7.4 (per protocol); one-session treatment: 7.4 (intention to treat), 7.6 (per protocol); on the standardised scale adjusted mean difference for cognitive-behavioural therapy compared with one-session treatment -0.123, 95% confidence interval -0.449 to 0.202 (intention to treat), mean difference -0.204, 95% confidence interval -0.579 to 0.171 (per protocol)]. These findings were wholly below the standardised non-inferiority limit of 0.4, which suggests that one-session treatment is non-inferior to cognitive-behavioural therapy. No between-group differences in secondary outcome measures were found. The health economics evaluation suggested that, compared with cognitive-behavioural therapy, one-session treatment marginally decreased the mean service use costs and maintained similar mean quality-adjusted life-year improvement. Nested qualitative evaluation found one-session treatment to be considered acceptable by those who received it, their parents/guardians and clinicians. No adverse events occurred as a result of phobia treatment. LIMITATIONS: The COVID-19 pandemic meant that 48 children and young people could not complete the primary outcome measure. Service waiting times resulted in some participants not starting therapy before follow-up. CONCLUSIONS: One-session treatment for specific phobia in UK-based child mental health treatment centres is as clinically effective as multisession cognitive-behavioural therapy and highly likely to be cost-saving. Future work could involve improving the implementation of one-session treatment through training and commissioning of improved care pathways. TRIAL REGISTRATION: This trial is registered as ISRCTN19883421. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 42. See the NIHR Journals Library website for further project information.

A phobia is an intense, ongoing fear of an everyday object or situation. The phobia causes distress and the person with the phobia avoids that object or situation. Many children and young people have phobias that affect their daily lives. Cognitive­behavioural therapy helps by changing what people do or think when they have a phobia and is the most common treatment approach. However, cognitive­behavioural therapy is expensive, takes time and is not always easy to get. Different treatments are needed to help children and young people with specific phobias. One such therapy is one-session treatment, which works in similar ways to cognitive­behavioural therapy but takes place over one main 3-hour session. Our study, called ASPECT (Alleviating Specific Phobias Experienced by Children Trial), compared these two treatments to examine whether or not one-session treatment is as effective as cognitive­behavioural therapy. Overall, 274 children and young people aged 7­16 years from 26 sites nationally helped with our research, of whom 268 received either cognitive­behavioural therapy or one-session treatment. The results at 6 months found that one-session treatment and cognitive­behavioural therapy worked as well as each other for treating phobias in children and young people. We also found evidence that one-session treatment is cheaper than cognitive­behavioural therapy. We spoke with children and young people, their parents/guardians and the therapists of the single-session treatment, and we found one-session treatment to be acceptable for their needs. Future research could explore how to make one-session treatment more easily available for children and young people with specific phobias because it can save time and money, and works just as well as cognitive­behavioural therapy.

Targeting the HuR Oncogenic Role with a New Class of Cytoplasmic Dimerization Inhibitors.

The development of novel therapeutics that exploit alterations in the activation state of key cellular signaling pathways due to mutations in upstream regulators has generated the field of personalized medicine. These first-generation efforts have focused on actionable mutations identified by deep sequencing of large numbers of tumor samples. We propose that a second-generation opportunity exists by exploiting key downstream "nodes of control" that contribute to oncogenesis and are inappropriately activated due to loss of upstream regulation and microenvironmental influences. The RNA-binding protein HuR represents such a node. Because HuR functionality in cancer cells is dependent on HuR dimerization and its nuclear/cytoplasmic shuttling, we developed a new class of molecules targeting HuR protein dimerization. A structure-activity relationship algorithm enabled development of inhibitors of HuR multimer formation that were soluble, had micromolar activity, and penetrated the blood-brain barrier. These inhibitors were evaluated for activity validation and specificity in a robust cell-based assay of HuR dimerization. SRI-42127, a molecule that met these criteria, inhibited HuR multimer formation across primary patient-derived glioblastoma xenolines (PDGx), leading to arrest of proliferation, induction of apoptosis, and inhibition of colony formation. SRI-42127 had favorable attributes with central nervous system penetration and inhibited tumor growth in mouse models. RNA and protein analysis of SRI-42127-treated PDGx xenolines across glioblastoma molecular subtypes confirmed attenuation of targets upregulated by HuR. These results highlight how focusing on key attributes of HuR that contribute to cancer progression, namely cytoplasmic localization and multimerization, has led to the development of a novel, highly effective inhibitor. SIGNIFICANCE: These findings utilize a cell-based mechanism of action assay with a structure-activity relationship compound development pathway to discover inhibitors that target HuR dimerization, a mechanism required for cancer promotion.

Modifying and validating the social responsiveness scale edition 2 for use with deaf children and young people.

A Delphi consensus methodology was used to adapt a screening tool, the Social Responsiveness Scale- 2 (SRS-2), for use with deaf children including those whose preferred communication method is sign language. Using this approach; 27 international experts (The Delphi International Expert Panel), on the topic of autism spectrum disorder (ASD) in deaf people, contributed to the review of item content. A criterion for agreement was set at 80% of experts on each item (with 75% acceptable in the final fourth round). The agreed modifications are discussed. The modified SRS-2 research adaptation for deaf people (referred to here as the "SRS-2 Deaf adaptation") was then translated into British Sign Language using a robust translation methodology and validated in England in a sample of 198 deaf children, 76 with Autism Spectrum Disorders (ASD) and 122 without ASD. The SRS-2 Deaf adaptation was compared blind to a NICE (National Institute for Health and Care Excellence) guideline standard clinical assessment. The area under the Receiver Operating (ROC) curve was 0.811 (95% CI: 0.753, 0.869), with an optimal cut-off value of 73, which gave a sensitivity of 82% and a specificity of 67%. The Cronbach Alpha coefficient was 0.968 suggesting high internal consistency. The Intraclass Correlation Coefficient was 0.897, supporting test-retest reliability. This performance is equivalent to similar instruments used for screening ASD in the hearing population.

Proof of concept of a smartphone app to support delivery of an intervention to facilitate mothers' mind-mindedness.

The present study reports on the first evaluation of a parenting intervention utilizing a smartphone app, BabyMind. The intervention aimed to facilitate mothers' mind-mindedness-attunement to their infants' internal states. Mothers in the intervention group (n = 90) used the BabyMind app from their infants' births and were followed up at age 6 months (n = 66). Mothers in the control group (n = 151) were recruited when their infants were age 6 months and had never used the BabyMind app. Mind-mindedness when interacting with their infants was significantly higher in intervention group mothers than in control group mothers. The intervention was equally effective in facilitating mind-mindedness in young and older mothers. These findings are discussed in terms of the potential for interventions utilizing smartphone apps to improve parenting and children's developmental outcome in vulnerable and hard-to-reach groups.