Robotic assessment of sensorimotor and cognitive deficits in patients with temporal lobe epilepsy.

OBJECTIVE: Individuals with temporal lobe epilepsy (TLE) frequently demonstrate impairments in executive function, working memory, and/or declarative memory. It is recommended that screening for cognitive impairment is undertaken in all people newly diagnosed with epilepsy. However, standard neuropsychological assessments are a limited resource and thus not available to all. Our study investigated the use of robotic technology (the Kinarm robot) for cognitive screening. METHODS: 27 participants with TLE (17 left) underwent both a brief neuropsychological screening and a robotic (Kinarm) assessment. The degree of impairments and correlations between standardized scores from both approaches to assessments were analysed across different neurocognitive domains. Performance was compared between people with left and right TLE to look for laterality effects. Finally, the association between the duration of epilepsy and performance was assessed. RESULTS: Across the 6 neurocognitive domains (attention, executive function, language, memory, motor and visuospatial) assessed by our neuropsychological screening, all showed scores that significantly correlated with Kinarm tasks assessing the same cognitive domains except language and memory that were not adequately assessed with Kinarm. Participants with right TLE performed worse on most tasks than those with left TLE, including both visuospatial (typically considered right hemisphere), and verbal memory and language tasks (typically considered left hemisphere). No correlations were found between the duration of epilepsy and either the neuropsychological screening or Kinarm assessment. SIGNIFICANCE: Our findings suggest that Kinarm may be a useful tool in screening for neurocognitive impairment in people with TLE. Further development may facilitate an easier and more rapid screening of cognition in people with epilepsy and distinguishing patterns of cognitive impairment.

Rates of Preterm Birth and Low Birth Weight in an Adolescent Obstetric Clinic: Achieving Health Equity Through Trauma-Informed Care.

Objectives: Adolescents who are pregnant and identify as Black are exposed to more societal harms that increase their and their offspring's risk for poor health outcomes. The Colorado Adolescent Maternity Program (CAMP) offers comprehensive, multidisciplinary (medical, behavioral health, nutrition, case management), trauma-informed obstetric care to pregnant adolescents to ensure the healthiest pregnancy and birth possible and pursue health equity. The present study aimed to examine ethnic and racial disparities in preterm birth and low birth weight before and after implementation of a trauma-informed model of care. Methods: Participants were 847 pregnant adolescents (ages 12-22 years; 41% self-identified as Hispanic, 32% as non-Hispanic Black, 21% as non-Hispanic white) who received prenatal treatment-as-usual (TAU) or trauma-informed treatment. Demographic information, mental health symptoms, and birth outcomes were abstracted from medical records. Results: Overall, findings provided support that implementation of a trauma-informed model of prenatal care led to equitable birth outcomes across racial and ethnic groups. Specifically, Black adolescents in the TAU group were more than twice as likely to deliver preterm or low birth weight infants compared with white and Hispanic adolescents. In the trauma-informed group, however, there were no statistical differences in birth outcomes across racial/ethnic groups, indicating an elimination of disparities in both preterm birth and low birth weight in this population. These more equitable birth outcomes occurred even in the context of adolescents of color having reported more severe depression symptoms postimplementation. Conclusions: These findings provide evidence that a health system-level intervention, herein trauma-informed obstetric care for adolescents, can play a meaningful role in the reduction of racial disparities in birth outcomes.

Secure attachment predicts lower societal cost amongst severely antisocial adolescents.

BACKGROUND: Social and economic costs associated with antisocial behaviour are well-established, but little is known about the potential costs savings/benefits of secure attachment in this high-risk group. We aimed to provide the first test of attachment quality as a distinct predictor of economic costs. METHODS: 111 adolescents (10-17 years of age, M = 15.0, SD = 1.6; 71% male) referred to young offender services due to high levels of antisocial behaviour were included. Costs were measured by detailed service-use interview, and attachment security to mother and father elicited through the Child Attachment Interview. The level of antisocial behaviour and callous-unemotional traits were assessed. Cost predictors were calculated using generalised linear models. RESULTS: Mean 12-months service costs were £5,368 (sd 5,769) per adolescent, with justice system and educational service costs being the main components. After adjusting for covariates, economic costs were predicted by attachment quality to fathers, with a difference of £2,655 per year between those with secure (£3,338) versus insecure attachment (£5,993); significant cost effects were not found for attachment quality to mothers. Higher levels of callous-unemotional traits, lower verbal IQ, higher levels of antisocial behaviour, and older age were also significant cost predictors. CONCLUSIONS: Secure attachment to fathers is a predictor of reduced public cost in adolescents with severe antisocial behaviour. This novel finding for severely antisocial youth extends previous findings in less antisocial children and underscores the public health and policy benefits of good caregiving quality and the value of population-level dissemination of evidence-based interventions that improve caregiving quality.

Assessment of Neurological Impairment and Recovery Using Statistical Models of Neurologically Healthy Behavior.

While many areas of medicine have benefited from the development of objective assessment tools and biomarkers, there have been comparatively few improvements in techniques used to assess brain function and dysfunction. Brain functions such as perception, cognition, and motor control are commonly measured using criteria-based, ordinal scales which can be coarse, have floor/ceiling effects, and often lack the precision to detect change. There is growing recognition that kinematic and kinetic-based measures are needed to quantify impairments following neurological injury such as stroke, in particular for clinical research and clinical trials. This paper will first consider the challenges with using criteria-based ordinal scales to quantify impairment and recovery. We then describe how kinematic-based measures can overcome many of these challenges and highlight a statistical approach to quantify kinematic measures of behavior based on performance of neurologically healthy individuals. We illustrate this approach with a visually-guided reaching task to highlight measures of impairment for individuals following stroke. Finally, there has been considerable controversy about the calculation of motor recovery following stroke. Here, we highlight how our statistical-based approach can provide an effective estimate of impairment and recovery.

Does Social and Economic Disadvantage Predict Lower Engagement with Parenting Interventions? An Integrative Analysis Using Individual Participant Data.

There is a social gradient to the determinants of health; low socioeconomic status (SES) has been linked to reduced educational attainment and employment prospects, which in turn affect physical and mental wellbeing. One goal of preventive interventions, such as parenting programs, is to reduce these health inequalities by supporting families with difficulties that are often patterned by SES. Despite these intentions, a recent individual participant data (IPD) meta-analysis of the Incredible Years (IY) parenting program found no evidence for differential benefit by socioeconomic disadvantage (Gardner et al. in Public Health Resesearch 5, 1-144, 2017). However, it did not examine whether this was influenced by engagement in the intervention. Using intervention arm data from this pooled dataset (13 trials; N = 1078), we examined whether there was an SES gradient to intervention attendance (an indicator of engagement). We ran mixed-effects Poisson regression models to estimate incidence rate ratios (IRRs) for program attendance for each of five (binary) markers of SES: low income; unemployment; low education status; teen parent; and lone parent status. The multilevel structure of the data allowed for comparison of within-trial and between-trial effects, including tests for contextual effects. We found evidence that low SES was associated with reduced attendance at parenting programs-an 8-19% reduction depending on the SES marker. However, there was no evidence that this association is impacted by differences in SES composition between trials or by the attendance levels of higher-SES families. The findings underscore the importance of developing and prioritizing strategies that enable engagement in parenting interventions and encourage program attendance by low-SES families.

A modified video-feedback intervention for carers of foster children aged 6 years and under with reactive attachment disorder: a feasibility study and pilot RCT.

BACKGROUND: Looked-after children are at risk of suboptimal attachment patterns and reactive attachment disorder. However, access to interventions varies widely and there are no evidence-based interventions for this disorder. OBJECTIVES: (1) To adapt an existing video-feedback intervention to meet the specific needs of foster children in the UK with reactive attachment symptoms, (2) to conduct a case series to road-test the treatment manual and study procedures, (3) to conduct a scoping study of the key hurdles in a pilot trial and (4) to conduct a pilot randomised controlled trial of the adapted intervention to determine the feasibility of a future full-scale trial. DESIGN: This was a mixed-methods study. The adapted treatment manual was developed with expert input and tested on a small case series. Qualitative interviews with key stakeholders were used in the scoping study in preparation for the trial and later with foster carers who received the new intervention. The final stage was a feasibility and pilot randomised controlled trial of the new intervention, compared with usual care. Researchers assessing the outcomes were blinded to group assignment. SETTING: The study was set in outpatient child and adolescent mental health services and partner social services departments. Sites included urban and rural/semirural areas. PARTICIPANTS: Participants were foster carers with children aged ≤ 6 years presenting with difficulties in the domain of reactive attachment disorder. Key stakeholders included children's services managers and mental health service practitioners in the scoping study. Foster carers who received the modified intervention participated in qualitative interviews. INTERVENTION: The video-feedback intervention to promote positive parenting and sensitive discipline is an extensively evaluated and effective treatment approach. This intervention was modified (based on the adapted version for foster care in the Netherlands) to suit the needs of young children with reactive attachment symptoms in foster care in the UK and was delivered to improve the sensitive responding of foster carers, foster carer-child relationships and child outcomes. The modified intervention was delivered in-home by trained mental health professionals over a period of 4-6 months. MAIN OUTCOME MEASURE: The main outcome was reactive attachment symptom scores on the Disturbances of Attachment Interview. RESULTS: A series of minor changes to the intervention programme were introduced, which focused on improving its suitability for the UK foster care context. Challenges in recruitment meant that, despite numerous modifications to the protocol and the inclusion of additional sites, only 30 families (target, n = 40) were recruited to the randomised controlled trial (15 allocated to each group). However, most other trial parameters were deemed feasible and acceptable, particularly the high levels of data and treatment completeness. All randomised families were available for baseline analyses, but two in the treatment arm were not available for post-treatment analyses. The revised intervention was positively received by practitioners and foster carers. LIMITATIONS: Only three-quarters of the target sample size was recruited. Furthermore, the sites' own exclusion of potential participants and the low return rates of screening questionnaires raise the possibility of non-randomness of non-responses. CONCLUSION: A larger-scale trial may be feasible, but only if recruitment barriers can be overcome. Dedicated resources to support recruitment within local authorities and wider inclusion criteria are recommended. Central resourcing of intervention capacity to supplement NHS staff is also recommended. TRIAL REGISTRATION: This trial is registered as ISRCTN18374094. 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. 35. See the NIHR Journals Library website for further project information.

Children in foster care typically have had a very difficult start in life, often as a result of abuse or neglect within their family of origin, and separation from caregivers. These children can find it difficult to trust new adults, and in some cases difficulties in attachment may justify a diagnosis of reactive attachment disorder. This disorder is a pattern of behaviour among young children who have received extremely insufficient early care, whereby they fail to seek or respond to comfort from carers when hurt or distressed, and they can be very withdrawn. There are currently no evidence-based treatments for reactive attachment disorder. The Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline is a treatment programme that was developed to promote secure attachments in young children and to help parents deal with difficult behaviour. A practitioner films the child and parent interacting at home and provides feedback in the following session. This treatment was previously adapted for use in foster care in the Netherlands. In this study, we modified the treatment further to ensure that it appropriately addressed the needs of young children in foster care in the UK who present with reactive attachment disorder symptoms. We then worked with local authorities and linked mental health services to develop a system for identifying young children in foster care in need of this treatment. Finally, we conducted a small (pilot) study to gather information about the best way to provide the modified treatment in this context. The revised treatment was positively received by practitioners and foster carers. The majority of the processes involved in running a trial also worked well (e.g. good levels of attendance at assessments and at the treatment sessions). However, we encountered significant difficulties in recruiting foster carers to the study. We concluded that a full-scale trial would be very valuable, and could potentially be undertaken if difficulties with recruitment are overcome. We recommend that greater resources be provided to local authorities to help them engage and recruit foster carers.

A good investment: longer-term cost savings of sensitive parenting in childhood.

BACKGROUND: Good quality parenting in early childhood is reliably associated with positive mental and physical health over the lifespan. The hypothesis that early parenting quality has significant long-term financial benefits has not been previously tested. METHODS: Design: Longitudinal study with follow-up from 2012 to 2016. SETTING: UK multicentre study cohort (London, South-East England). PARTICIPANTS: 174 young people drawn from 2 samples, one at moderate risk of poor outcomes and one at high risk, assessed aged 4-6 years then followed up in early adolescence (mean age 12.1 years). MEASURES: The primary outcome was total costs: health, social care, extra school support, out-of-home placements and family-born expenditure, determined through semistructured economic interviews. Early parenting quality was independently assessed through direct observation of parent-child interaction. RESULTS: Costs were lower for youths exposed to more sensitive parenting (most sensitive quartile mean £1,619, least sensitive quartile mean £21,763; p < .001). Costs were spread across personal family expenditure and education, health, social and justice services. The cost difference remained significant after controlling for several potential confounders. These included demographic variables (family poverty, parental education); exposure to child abuse; and child/young person variables including level of antisocial behaviour in both childhood and adolescence, IQ and attachment security. CONCLUSIONS: This study is the first showing that more sensitive early parental care predicts lower costs to society many years later, independent of poverty, child and youth antisocial behaviour levels and IQ. Savings are likely to increase as individuals grow older since early parenting quality predicts health, behavioural and occupational outcomes in adulthood. The findings provide novel evidence for the public health impact of early caregiving quality and likely financial benefits of improving it.

Principal Components Analysis Using Data Collected From Healthy Individuals on Two Robotic Assessment Platforms Yields Similar Behavioral Patterns.

BACKGROUND: Kinarm Standard Tests (KSTs) is a suite of upper limb tasks to assess sensory, motor, and cognitive functions, which produces granular performance data that reflect spatial and temporal aspects of behavior (>100 variables per individual). We have previously used principal component analysis (PCA) to reduce the dimensionality of multivariate data using the Kinarm End-Point Lab (EP). Here, we performed PCA using data from the Kinarm Exoskeleton Lab (EXO), and determined agreement of PCA results across EP and EXO platforms in healthy participants. We additionally examined whether further dimensionality reduction was possible by using PCA across behavioral tasks. METHODS: Healthy participants were assessed using the Kinarm EXO (N = 469) and EP (N = 170-200). Four behavioral tasks (six assessments in total) were performed that quantified arm sensory and motor function, including position sense [Arm Position Matching (APM)] and three motor tasks [Visually Guided Reaching (VGR), Object Hit (OH), and Object Hit and Avoid (OHA)]. The number of components to include per task was determined from scree plots and parallel analysis, and rotation type (orthogonal vs. oblique) was decided on a per-task basis. To assess agreement, we compared principal components (PCs) across platforms using distance correlation. We additionally considered inter-task interactions in EXO data by performing PCA across all six behavioral assessments. RESULTS: By applying PCA on a per task basis to data collected using the EXO, the number of behavioral parameters were substantially reduced by 58-75% while accounting for 76-87% of the variance. These results compared well to the EP analysis, and we found good-to-excellent agreement values (0.75-0.99) between PCs from the EXO and those from the EP. Finally, we were able to reduce the dimensionality of the EXO data across tasks down to 16 components out of a total of 76 behavioral parameters, which represents a reduction of 79% while accounting for 73% of the total variance. CONCLUSION: PCA of Kinarm robotic assessment appears to capture similar relationships between kinematic features in healthy individuals and is agnostic to the robotic platform used for collection. Further work is needed to investigate the use of PCA-based data reduction for the characterization of neurological deficits in clinical populations.

A video-feedback parenting intervention to prevent enduring behaviour problems in at-risk children aged 12-36 months: the Healthy Start, Happy Start RCT.

BACKGROUND: Behaviour problems emerge early in childhood and place children at risk for later psychopathology. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of a parenting intervention to prevent enduring behaviour problems in young children. DESIGN: A pragmatic, assessor-blinded, multisite, two-arm, parallel-group randomised controlled trial. SETTING: Health visiting services in six NHS trusts in England. PARTICIPANTS: A total of 300 at-risk children aged 12-36 months and their parents/caregivers. INTERVENTIONS: Families were allocated in a 1 : 1 ratio to six sessions of Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) plus usual care or usual care alone. MAIN OUTCOME MEASURES: The primary outcome was the Preschool Parental Account of Children's Symptoms, which is a structured interview of behaviour symptoms. Secondary outcomes included caregiver-reported total problems on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The intervention effect was estimated using linear regression. Health and social care service use was recorded using the Child and Adolescent Service Use Schedule and cost-effectiveness was explored using the Preschool Parental Account of Children's Symptoms. RESULTS: In total, 300 families were randomised: 151 to VIPP-SD plus usual care and 149 to usual care alone. Follow-up data were available for 286 (VIPP-SD, n = 140; usual care, n = 146) participants and 282 (VIPP-SD, n = 140; usual care, n = 142) participants at 5 and 24 months, respectively. At the post-treatment (primary outcome) follow-up, a group difference of 2.03 on Preschool Parental Account of Children's Symptoms (95% confidence interval 0.06 to 4.01; p = 0.04) indicated a positive treatment effect on behaviour problems (Cohen's d = 0.20, 95% confidence interval 0.01 to 0.40). The effect was strongest for children's conduct [1.61, 95% confidence interval 0.44 to 2.78; p = 0.007 (d = 0.30, 95% confidence interval 0.08 to 0.51)] versus attention deficit hyperactivity disorder symptoms [0.29, 95% confidence interval -1.06 to 1.65; p = 0.67 (d = 0.05, 95% confidence interval -0.17 to 0.27)]. The Child Behaviour Checklist [3.24, 95% confidence interval -0.06 to 6.54; p = 0.05 (d = 0.15, 95% confidence interval 0.00 to 0.31)] and the Strengths and Difficulties Questionnaire [0.93, 95% confidence interval -0.03 to 1.9; p = 0.06 (d = 0.18, 95% confidence interval -0.01 to 0.36)] demonstrated similar positive treatment effects to those found for the Preschool Parental Account of Children's Symptoms. At 24 months, the group difference on the Preschool Parental Account of Children's Symptoms was 1.73 [95% confidence interval -0.24 to 3.71; p = 0.08 (d = 0.17, 95% confidence interval -0.02 to 0.37)]; the effect remained strongest for conduct [1.07, 95% confidence interval -0.06 to 2.20; p = 0.06 (d = 0.20, 95% confidence interval -0.01 to 0.42)] versus attention deficit hyperactivity disorder symptoms [0.62, 95% confidence interval -0.60 to 1.84; p = 0.32 (d = 0.10, 95% confidence interval -0.10 to 0.30)], with little evidence of an effect on the Child Behaviour Checklist and the Strengths and Difficulties Questionnaire. The primary economic analysis showed better outcomes in the VIPP-SD group at 24 months, but also higher costs than the usual-care group (adjusted mean difference £1450, 95% confidence interval £619 to £2281). No treatment- or trial-related adverse events were reported. The probability of VIPP-SD being cost-effective compared with usual care at the 24-month follow-up increased as willingness to pay for improvements on the Preschool Parental Account of Children's Symptoms increased, with VIPP-SD having the higher probability of being cost-effective at willingness-to-pay values above £800 per 1-point improvement on the Preschool Parental Account of Children's Symptoms. LIMITATIONS: The proportion of participants with graduate-level qualifications was higher than among the general public. CONCLUSIONS: VIPP-SD is effective in reducing behaviour problems in young children when delivered by health visiting teams. Most of the effect of VIPP-SD appears to be retained over 24 months. However, we can be less certain about its value for money. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58327365. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 29. See the NIHR Journals Library website for further project information.

Behaviour problems in young children are common and are linked to mental and physical health problems, and educational and social difficulties. An important factor that influences the development of behaviour problems is the quality of care that children receive from their caregivers. This study aimed to test if a six-session parenting programme [called Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD)] reduced behaviour problems in children aged 1 or 2 years who were showing early signs of behaviour problems (e.g. restlessness, impulsivity, tantrums and aggression). VIPP-SD supports caregivers in responding to their child's communication and behaviour. A total of 300 families participated. All families continued to access usual health-care services (e.g. health visitors and general practitioners), but half of the families were randomly allocated to also receive the VIPP-SD programme. We visited all families when the study started, and at 5 and 24 months to see if the children whose families received VIPP-SD showed fewer behaviour problems. We measured the children's behaviour by completing interviews and questionnaires with their caregivers. We also analysed whether or not VIPP-SD was good value for money compared with existing services. We did this by comparing the cost of all of the standard health and community services that families accessed during their time in the study, taking account of the impact that VIPP-SD had on children's behaviour. The children in the VIPP-SD group had lower levels of behaviour problems following the programme than children whose parents did not receive the programme. On average, VIPP-SD children scored 2 points lower on the main measure of behaviour; an example difference would be tantrums being rated as mild rather than severe. By the 2-year visit, the VIPP-SD children continued to show lower levels of behaviour problems. It is less clear whether or not VIPP-SD is good value for money, as this depends on how much money policy-makers are willing to invest for reductions in behaviour problems. Overall, there is strong evidence that the VIPP-SD programme is effective in reducing behaviour problems in the short term. Most of this benefit appears to be maintained for the following 2 years. However, we are less certain about the long-term effect and the VIPP-SD's value for money.

Assessment of spatiotemporal gait parameters using a deep learning algorithm-based markerless motion capture system.

Spatiotemporal parameters can characterize the gait patterns of individuals, allowing assessment of their health status and detection of clinically meaningful changes in their gait. Video-based markerless motion capture is a user-friendly, inexpensive, and widely applicable technology that could reduce the barriers to measuring spatiotemporal gait parameters in clinical and more diverse settings. Two studies were performed to determine whether gait parameters measured using markerless motion capture demonstrate concurrent validity with those measured using marker-based motion capture and a pressure-sensitive gait mat. For the first study, thirty healthy young adults performed treadmill gait at self-selected speeds while marker-based motion capture and synchronized video data were recorded simultaneously. For the second study, twenty-five healthy young adults performed over-ground gait at self-selected speeds while footfalls were recorded using a gait mat and synchronized video data were recorded simultaneously. Kinematic heel-strike and toe-off gait events were used to identify the same gait cycles between systems. Nine spatiotemporal gait parameters were measured by each system and directly compared between systems. Measurements were compared using Bland-Altman methods, mean differences, Pearson correlation coefficients, and intraclass correlation coefficients. The results indicate that markerless measurements of spatiotemporal gait parameters have good to excellent agreement with marker-based motion capture and gait mat systems, except for stance time and double limb support time relative to both systems and stride width relative to the gait mat. These findings indicate that markerless motion capture can adequately measure spatiotemporal gait parameters of healthy young adults during treadmill and over-ground gait.

Robotic Assessment of Upper Limb Function in a Nonhuman Primate Model of Chronic Stroke.

Stroke is a leading cause of death and disability worldwide and survivors are frequently left with long-term disabilities that diminish their autonomy and result in the need for chronic care. There is an urgent need for the development of therapies that improve stroke recovery, as well as accurate and quantitative tools to measure function. Nonhuman primates closely resemble humans in neuroanatomy and upper limb function and may be crucial in randomized pre-clinical trials for testing the efficacy of stroke therapies. To test the feasibility of robotic assessment of motor function in a NHP model of stroke, two cynomolgus macaques were trained to perform a visually guided reaching task and were also assessed in a passive stretch task using the Kinarm robot. Strokes were then induced in these animals by transiently occluding the middle cerebral artery, and their motor performance on the same tasks was assessed after recovery. Relative to pre-stroke performance, post-stroke hand movements of the affected limb became slower and less accurate. Regression analyses revealed both recovered and compensatory movements to complete movements in different spatial directions. Lastly, we noted decreased range of motion in the elbow joint of the affected limb post-stroke associated with spasticity during passive stretch. Taken together, these studies highlight that sensorimotor deficits in reaching movements following stroke in cynomolgus macaques resemble those in human patients and validate the use of robotic assessment tools in a nonhuman primate model of stroke for identifying and characterizing such deficits.

An intervention for parents with severe personality difficulties whose children have mental health problems: a feasibility RCT.

BACKGROUND: The children of parents with severe personality difficulties have greater risk of significant mental health problems. Existing care is poorly co-ordinated, with limited effectiveness. A specialised parenting intervention may improve child and parenting outcomes, reduce family morbidity and lower the service costs. OBJECTIVES: To develop a specialised parenting intervention for parents affected by severe personality difficulties who have children with mental health problems and to conduct a feasibility trial. DESIGN: A pragmatic, mixed-methods design to develop and pilot a specialised parenting intervention, Helping Families Programme-Modified, and to conduct a randomised feasibility trial with process evaluation. Initial cost-effectiveness was assessed using UK NHS/Personal Social Services and societal perspectives, generating quality-adjusted life-years. Researchers collecting quantitative data were masked to participant allocation. SETTING: Two NHS mental health trusts and concomitant children's social care services. PARTICIPANTS: Parents who met the following criteria: (1) the primary caregiver of the index child, (2) aged 18-65 years, (3) have severe personality difficulties, (4) proficient in English and (5) capable of providing informed consent. Index children who met the following criteria: (1) aged 3-11 years, (2) living with index parent and (3) have significant emotional/behavioural difficulties. Exclusion criteria were (1) having coexisting psychosis, (2) participating in another parenting intervention, (3) receiving inpatient care, (4) having insufficient language/cognitive abilities, (5) having child developmental disorder, (6) care proceedings and (7) index child not residing with index parent. INTERVENTION: The Helping Families Programme-Modified - a 16-session intervention using structured, goal-orientated strategies and collaborative therapeutic methods to improve parenting, and child and parent functioning. Usual care - standard care augmented by a single psychoeducational session. MAIN OUTCOME MEASURES: Trial feasibility - rates of recruitment, eligibility, allocation, retention, data completion and experience. Intervention acceptability - rates of acceptance, completion, alliance (Working Alliance Inventory-Short Revised) and experience. Outcomes - child (assessed via Concerns About My Child, Eyberg Child Behaviour Inventory, Child Behaviour Checklist-Internalising Scale), parenting (assessed via the Arnold-O'Leary Parenting Scale, Kansas Parental Satisfaction Scale), parent (assessed via the Symptom Checklist-27), and health economics (assessed via the Client Service Receipt Inventory, EuroQol-5 Dimensions). RESULTS: The findings broadly supported trial feasibility using non-diagnostic screening criteria. Parents were mainly referred from one site (75.0%). Site and participant factors delayed recruitment. An estimate of eligible parents was not obtained. Of the 86 parents referred, 60 (69.7%) completed screening and 48 of these (80.0%) were recruited. Participants experienced significant disadvantage and multiple morbidity. The Helping Families Programme-Modified uptake (87.5%) was higher than usual-care uptake (62.5%). Trial retention (66.7%, 95% confidence interval 51.6% to 79.6%) exceeded the a priori rate. Process findings highlighted the impact of random allocation and the negative effects on retention. The Helping Families Programme-Modified was acceptable, with duration of delivery longer than planned, whereas the usual-care condition was less acceptable. At initial follow-up, effects on child and parenting outcomes were detected across both arms, with a potential outcome advantage for the Helping Families Programme-Modified (effect size range 0.0-1.3). For parental quality-adjusted life-years, the Helping Families Programme-Modified dominated usual care, and child quality-adjusted life-years resulted in higher costs and more quality-adjusted life-years. At second follow-up, the Helping Families Programme-Modified was associated with higher costs and more quality-adjusted life-years than usual care. For child quality-adjusted life-years, when controlled for baseline EuroQol-5 Dimensions, three-level version, usual care dominated the Helping Families Programme-Modified. No serious adverse events were reported. CONCLUSION: The Helping Families Programme-Modified is an acceptable specialised parenting intervention. Trial methods using non-diagnostic criteria were largely supported. For future work, a definitive efficacy trial should consider site selection, recruitment methods, intervention efficiency and revised comparator condition. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14573230. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 14. See the NIHR Journals Library website for further project information.

Parents affected by personality difficulties experience strong, overwhelming emotions and struggle in their personal and social relationships. These difficulties can interfere with their ability to provide stable, safe and warm parenting, which increases the risk of their children developing mental health problems. This research developed the Helping Families Programme-Modified, a new parenting intervention designed to help parents with severe personality difficulties who have children with mental health problems. Parents received 16 home-based appointments to learn new parenting skills and improve their children's difficulties. The research assessed how the Helping Families Programme-Modified worked in practice and the viability of evaluation methods. A short questionnaire assessing personality difficulties, rather than a lengthy diagnostic interview, was more effective and acceptable for identifying parents who may benefit from the Helping Families Programme-Modified. Parents taking part had high levels of personal, family and social problems. This slowed the rate at which parents agreed to take part in the evaluation and lengthened the intervention period. The research tested parent agreement to being randomly allocated to receive either the Helping Families Programme-Modified or usual care plus a specially designed parenting appointment. Although this random allocation was feasible, parents were disappointed when they did not receive the Helping Families Programme-Modified. They often felt overwhelmed by family difficulties and lacked other suitable services. These parents were less likely to take up the additional parenting appointment available or to provide subsequent research information, which affected the certainty of the research findings. Parents receiving the Helping Families Programme-Modified or usual care reported improvements, with a potentially greater impact on parents and children, and better acceptability, for the new intervention. Parents generally supported the tailored, home-based approach of the Helping Families Programme-Modified, and they valued its content, therapist skills and persistence. It was uncertain whether the new intervention increased or reduced service costs. These results will be used to plan the most suitable methods for a large-scale evaluation of the Helping Families Programme-Modified.

The enhanced immunopharmacology of VIB4920, a novel Tn3 fusion protein and CD40L antagonist, and assessment of its safety profile in cynomolgus monkeys.

BACKGROUND AND PURPOSE: Inhibition of the T- and B-cell interaction through the CD40/CD40 ligand (L) axis is a favourable approach for inflammatory disease treatment. Clinical studies of anti-CD40L molecules in autoimmune diseases have met challenges because of thromboembolic events and adverse haemostasis. VIB4920 (formerly MEDI4920) is a novel CD40L antagonist and Tn3 fusion protein designed to prevent adverse haemostasis and immunopharmacology. We evaluated the pharmacokinetics, activity and toxicity of VIB4920 in monkeys. EXPERIMENTAL APPROACH: Cynomolgus monkeys received i.v. or s.c. 5-300 mg·kg-1 VIB4920 or vehicle, once weekly for 1 month (Studies 1 and 2) or 28 weeks (Study 3). VIB4920 exposure and bioavailability were determined using pharmacokinetic analyses, and immune cell population changes via flow cytometry. Pharmacological activity was evaluated by measuring the animals' capacity to elicit an immune response to keyhole limpet haemocyanin (KLH) and tetanus toxoid (TT). KEY RESULTS: VIB4920 demonstrated linear pharmacokinetics at multiple doses. Lymphocyte, monocyte, cytotoxic T-cell and NK cell counts were not significantly different between treatment groups. B-cell counts reduced dose-dependently and the T-cell dependent antibody response to KLH was suppressed by VIB4920 dose-dependently. The recall response to TT was similar across treatment groups. No thromboembolic events or symptoms of immune system dysfunctionality were observed. CONCLUSIONS AND IMPLICATIONS: VIB4920 demonstrated an acceptable safety profile in monkeys. VIB4920 showed favourable pharmacokinetics, dose-dependent inhibition of a neoantigen-specific immune response and no adverse effects on immune function following long-term use. Our data support the use of VIB4920 in clinical trials.

Movement kinematics and proprioception in post-stroke spasticity: assessment using the Kinarm robotic exoskeleton.

BACKGROUND: Motor impairment after stroke interferes with performance of everyday activities. Upper limb spasticity may further disrupt the movement patterns that enable optimal function; however, the specific features of these altered movement patterns, which differentiate individuals with and without spasticity, have not been fully identified. This study aimed to characterize the kinematic and proprioceptive deficits of individuals with upper limb spasticity after stroke using the Kinarm robotic exoskeleton. METHODS: Upper limb function was characterized using two tasks: Visually Guided Reaching, in which participants moved the limb from a central target to 1 of 4 or 1 of 8 outer targets when cued (measuring reaching function) and Arm Position Matching, in which participants moved the less-affected arm to mirror match the position of the affected arm (measuring proprioception), which was passively moved to 1 of 4 or 1 of 9 different positions. Comparisons were made between individuals with (n = 35) and without (n = 35) upper limb post-stroke spasticity. RESULTS: Statistically significant differences in affected limb performance between groups were observed in reaching-specific measures characterizing movement time and movement speed, as well as an overall metric for the Visually Guided Reaching task. While both groups demonstrated deficits in proprioception compared to normative values, no differences were observed between groups. Modified Ashworth Scale score was significantly correlated with these same measures. CONCLUSIONS: The findings indicate that individuals with spasticity experience greater deficits in temporal features of movement while reaching, but not in proprioception in comparison to individuals with post-stroke motor impairment without spasticity. Temporal features of movement can be potential targets for rehabilitation in individuals with upper limb spasticity after stroke.

The cost of love: financial consequences of insecure attachment in antisocial youth.

BACKGROUND: Knowing that your parent or caregiver will be there for you in times of emotional need and distress is a core aspect of the human experience of feeling loved and being securely attached. In contrast, an insecure attachment pattern is found in many antisocial youth and is related to less sensitive caregiving. Such youth are often distrustful of adults and authority figures, and are at high risk of poor outcomes. As they become adults, they require extensive health, social and economic support, costing society ten times more than their well-adjusted peers. However, it is not known whether insecure attachment itself is associated with higher costs in at-risk youth, independently of potential confounders, nor whether cost differences are already beginning to emerge early in adolescence. METHODS: Sample: A total of 174 young people followed up aged 9-17 years (mean 12.1, SD 1.8): 85 recruited with moderate antisocial behaviour (80th percentile) from a school screen aged 4-6 years; 89 clinically referred with very high antisocial behaviour (98th percentile) aged 3-7 years. MEASURES: Costs by detailed health economic and service-use interview; attachment security to mother and father from interview; diagnostic interviews for oppositional and conduct problems; self-reported delinquent behaviour. RESULTS: Costs were greater for youth insecurely attached to their mothers (secure £6,743, insecure £10,199, p = .001) and more so to fathers (secure £1,353, insecure £13,978, p < .001). These differences remained significant (mother p = .019, father p < .001) after adjusting for confounders, notably family income and education, intelligence and antisocial behaviour severity. CONCLUSIONS: Attachment insecurity is a significant predictor of public cost in at-risk youth, even after accounting for covariates. Since adolescent attachment security is influenced by caregiving quality earlier in childhood, these findings add support to the public health case for early parenting interventions to improve child outcomes and reduce the financial burden on society.

Equity effects of parenting interventions for child conduct problems: a pan-European individual participant data meta-analysis.

BACKGROUND: Childhood conduct problems are a costly public health problem and are five times more common in socially disadvantaged groups than they are in advantaged groups. Untreated, conduct problems have a poor prognosis, with increasing gaps between socioeconomic groups, and high rates of subsequent criminality. Incredible Years is a high quality parenting programme for reducing conduct problems and is widely disseminated in Europe. Many trials have shown Incredible Years to be effective but the potential effects of parenting interventions on social inequality are unknown. Some behavioural interventions (eg, smoking cessation programmes), although beneficial overall, can widen inequality gaps. Because single trials and aggregate-level meta-analyses are ill equipped for examining differential intervention (moderator) effects, we pooled individual-level trial data to assess the effects of Incredible Years on social equity. METHODS: We did a systematic review and individual participant data meta-analysis by searching CINAHL, Embase, Global Health, Medline, and PsycINFO, for studies published from inception to March 15, 2019. We also searched the Incredible Years website library and consulted with experts, including the European Incredible Years mentors' network. We included data from all completed randomised trials of the Incredible Years parenting intervention in Europe that included children aged 1-12 years, including unpublished trials, without restriction on publication year or outcome measures. We included prevention (selective or universal) and treatment or indicated prevention trials (for children diagnosed or above the clinical cutoff for conduct problems). We excluded trials or conditions within trials that were not randomised, included additional non-parenting material (eg, child-focused interventions), or were abbreviated, non-standard versions of the usual Incredible Years intervention of 12-14 weekly sessions. We requested individual participant data from the study authors. The primary outcome was child conduct problems, assessed using the Eyberg Child Behavior Inventory Intensity (ECBI-I) scale. Moderators were analysed using multilevel modelling with multiple imputation. FINDINGS: Of 15 European trials of Incredible Years parenting programmes (n=1696 children), individual participant data were unavailable for one trial and one trial did not assess the primary outcome. Children were aged 2-10 years (median 5·1), 492 (30%) of 1651 children were from an ethnic minority and 931 (58%) of 1614 were from low-income families. Families who received the Incredible Years intervention reported an overall reduction in child conduct problems (13·5 points on the ECBI-I scale, 95% CI 10·9-16·1). There were no differential effects by family disadvantage (indicated by poverty, lone parenthood, teenage parenthood, household joblessness, or low education), or ethnic minority status. INTERPRETATION: We found no evidence for differential effects by social disadvantage, suggesting that Incredible Years is unlikely to widen socioeconomic inequalities in conduct problems. Furthermore, the programme might be an important tool for reducing social disparities and improving poor long-term outcomes in disadvantaged families because follow-up studies indicate that benefits persist. Clinicians and commissioners can be reassured that the programme is similarly effective for families from different backgrounds. FUNDING: UK National Institute for Health Research.

Addressing Race, Culture, and Structural Inequality in Medical Education: A Guide for Revising Teaching Cases.

PROBLEM: Sociodemographic identities, including race, culture, ethnicity, gender, and sexual orientation (race and culture), are recognized as important determinants of health, with significant impacts on patients' health outcomes, but teaching medical students about this is challenging. The authors sought to identify areas for improvement in delivery of critical content about race, culture, structural inequalities, and health disparities within a set of virtual patient cases used by U.S. medical schools and develop revision guidelines. APPROACH: A workgroup (medical students and faculty) conducted a literature review in 2017 to identify challenges and best practices for teaching and learning about race and culture in medicine. Using an analytic framework informed by this review, they analyzed 63 Aquifer virtual patient teaching cases for effectiveness of the presentation of race and culture, resulting in six main themes describing common mistakes or pitfalls. They then developed an evidence-based guide for systematic case revision. OUTCOMES: The authors present a novel, practical guide for medical educators to use to revise existing teaching cases and improve the delivery of critical concepts surrounding race and culture. This guide includes fundamental definitions and six sections to guide structured case revision based on the main themes. It includes examples of language, suggested edits, and the rationale and evidence for recommendations. NEXT STEPS: Feedback from faculty and students regarding implementation of the guide and delivery of revised content in Aquifer cases will be critical in determining the guide's effectiveness. This structured guide may be adapted to a variety of teaching modalities in medicine.

Robotic Assessment of Motor, Sensory, and Cognitive Function in Acute Sport-Related Concussion and Recovery.

There is a need for better tools to objectively, reliably, and precisely assess neurological function after sport-related concussion (SRC). The aim of this study was to use a robotic device (Kinesiological Instrument for Normal and Altered Reaching Movements; KINARM) to quantify neurological impairments in athletes acutely and when clinically asymptomatic post-SRC. Robotic assessments included five KINARM standard tasks that evaluate aspects of motor, sensory, and cognitive function. We hypothesized that acutely concussed athletes would demonstrate significant rates of impairment on the robotic assessment, and that impairments would be associated with acute symptom severity. Pre-season assessments were conducted from 2011 to 2016 on 1051 athletes. Eighty-four athletes were reassessed acutely (≤10 days post-injury) and while symptomatic post-SRC and 89 when clinically asymptomatic. Forty-four parameters were measured from the KINARM assessment to characterize neurological function. Reliable change indices (80% confidence interval) identified impairments in healthy and concussed individuals for each parameter. In concussed individuals, impairment rate varied across parameters from 4% to 27% at the acute time point and from 2% to 18% when clinically asymptomatic. Healthy athlete impairment rates were between 2% and 16% across all testing time points. We identified relationships between acute symptom severity and task performance for only two parameters, both of which evaluated attributes of motor function. Overall, the KINARM identified impairments in motor, sensory, and cognitive function in athletes with SRC; however, impairment rates were low and largely did not relate to symptom severity. More complex tasks may be necessary to identify potentially subtle neurological impairments post-SRC.

Test-retest reliability of the KINARM end-point robot for assessment of sensory, motor and neurocognitive function in young adult athletes.

BACKGROUND: Current assessment tools for sport-related concussion are limited by a reliance on subjective interpretation and patient symptom reporting. Robotic assessments may provide more objective and precise measures of neurological function than traditional clinical tests. OBJECTIVE: To determine the reliability of assessments of sensory, motor and cognitive function conducted with the KINARM end-point robotic device in young adult elite athletes. METHODS: Sixty-four randomly selected healthy, young adult elite athletes participated. Twenty-five individuals (25 M, mean age±SD, 20.2±2.1 years) participated in a within-season study, where three assessments were conducted within a single season (assessments labeled by session: S1, S2, S3). An additional 39 individuals (28M; 22.8±6.0 years) participated in a year-to-year study, where annual pre-season assessments were conducted for three consecutive seasons (assessments labeled by year: Y1, Y2, Y3). Forty-four parameters from five robotic tasks (Visually Guided Reaching, Position Matching, Object Hit, Object Hit and Avoid, and Trail Making B) and overall Task Scores describing performance on each task were quantified. RESULTS: Test-retest reliability was determined by intra-class correlation coefficients (ICCs) between the first and second, and second and third assessments. In the within-season study, ICCs were ≥0.50 for 68% of parameters between S1 and S2, 80% of parameters between S2 and S3, and for three of the five Task Scores both between S1 and S2, and S2 and S3. In the year-to-year study, ICCs were ≥0.50 for 64% of parameters between Y1 and Y2, 82% of parameters between Y2 and Y3, and for four of the five Task Scores both between Y1 and Y2, and Y2 and Y3. CONCLUSIONS: Overall, the results suggest moderate-to-good test-retest reliability for the majority of parameters measured by the KINARM robot in healthy young adult elite athletes. Future work will consider the potential use of this information for clinical assessment of concussion-related neurological deficits.

Multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour (START): a pragmatic, randomised controlled, superiority trial.

BACKGROUND: Adolescent antisocial behaviour is a major health and social problem. Studies in the USA have shown that multisystemic therapy reduces such behaviour and the number of criminal offences committed by this group. However, findings outside the USA are equivocal. We aimed to assess the effectiveness and cost-effectiveness of multisystemic therapy versus management as usual in the treatment of adolescent antisocial behaviour. METHODS: We did an 18 month, multisite, pragmatic, randomised controlled, superiority trial in England. Eligible participants aged 11-17 years with moderate-to-severe antisocial behaviour had at least three severity criteria indicating past difficulties across several settings and one of five general inclusion criteria for antisocial behaviour. We randomly assigned families (1:1) using stochastic minimisation, stratifying for treatment centre, sex, age at enrolment to study, and age at onset of antisocial behaviour, to receive either management as usual or 3-5 months of multisystemic therapy followed by management as usual. Research assistants and investigators were masked to treatment allocation; the participants could not be masked. The primary outcome was out-of-home placement at 18 months. The primary analysis included all randomised participants for whom data were available. This trial is registered, number ISRCTN77132214. Follow-up of the trial is still ongoing. FINDINGS: Between Feb 4, 2010, and Sept 1, 2012, 1076 families were referred to nine multi-agency panels, 684 of whom were assigned to management as usual (n=342) or multisystemic therapy followed by management as usual (n=342). At 18 months, the proportion of participants in out-of-home placement was not significantly different between the groups (13% [43/340] in the multisystemic therapy group vs 11% [36/335] in the management-as-usual group; odds ratio 1·25, 95% CI 0·77-2·05; p=0·37). INTERPRETATION: The findings do not support that multisystemic therapy should be used over management as usual as the intervention of choice for adolescents with moderate-to-severe antisocial behaviour. FUNDING: Department for Children, Schools and Families, Department of Health.