Study Preregistration: Individual Participant Data Meta-Analysis: Individual Differences in Mediators of Parenting Program Effects on Disruptive Behavior.

Parenting programs are the most widely used strategy to prevent and reduce children's disruptive behavior,1 and yet we know very little about what exact changes in parenting behavior underlie program effects on disruptive child behavior. In fact, most studies have been unable to identify any mediators of parenting program effects.2 This is likely because, at least in part, individual trials tend to be underpowered to detect mediation effects,3 and are unable to take the known heterogeneity in program effects4 into account.

Integrating Mental Health Care in Ambulatory Obstetrical Practices: Strategies and Models.

Perinatal mental health is recognized as a priority component of obstetrical care. Perinatal patients often turn to their obstetrician for help with mental health concerns as they view them as their primary health care provider. Unfortunately, obstetricians face challenges in providing adequate support due to time constraints and limited expertise. Integrated behavioral health care offers a collaborative and cost-effective solution to enhance patient care and clinician satisfaction. Integrated behavioral health clinicians possess fundamental skills to care for patients throughout the reproductive lifespan and assist obstetricians in identifying and managing common mood concerns.

Recognition and management of children and adolescents with conduct disorder: a real-world data study from four western countries.

BACKGROUND: Conduct disorders (CD) are among the most frequent psychiatric disorders in children and adolescents, with an estimated worldwide prevalence in the community of 2-4%. Evidence-based psychological outpatient treatment leads to significant improvement in about two-thirds of cases. However, there seems to be considerable variation in rates of CD diagnoses and implementation of evidence-based interventions between nations. The aim of this study was to compare administrative prevalence and treatment patterns for CD in children and adolescents seen in health care systems across four Western countries (Denmark, Germany, Norway, and the USA). METHODS: Cross-sectional observational study using healthcare data to identify children and adolescents (aged 0-19 years) with an ICD-10 code for CD within the calendar year 2018. Within each country's study population, the prevalence of CD, psychiatric comorbidity, psychopharmacological treatment, and psychiatric hospitalisation was calculated. RESULTS: The prevalence of diagnosed CD differed 31-fold between countries: 0.1% (Denmark), 0.3% (Norway), 1.1% (USA) and 3.1% (Germany), with a male/female ratio of 2.0-2.5:1. The rate of psychiatric comorbidity ranged from 69.7 to 86.1%, with attention-deficit/hyperactivity disorder being most common. Between 4.0% (Germany) and 12.2% (USA) of youths with a CD diagnosis were prescribed antipsychotic medication, and 1.2% (Norway) to 12.5% (Germany) underwent psychiatric hospitalisation. CONCLUSION: Recognition and characteristics of youths diagnosed with CD varied greatly by country. In some countries, the administrative prevalence of diagnosed CD was markedly lower than the average estimated worldwide prevalence. This variation might reflect country-specific differences in CD prevalence, referral thresholds for mental health care, diagnostic tradition, and international variation in service organisation, CD recognition, and availability of treatment offers for youths with CD. The rather high rates of antipsychotic prescription and hospitalisation in some countries are remarkable, due to the lack of evidence for these therapeutic approaches. These findings stress the need of prioritising evidence-based treatment options in CD. Future research should focus on possible reasons for inter-country variation in recognition and management of CD, and also address possible differences in patient-level outcomes.

Rapid Online Corrections for Proprioceptive and Visual Perturbations Recruit Similar Circuits in Primary Motor Cortex.

An important aspect of motor function is our ability to rapidly generate goal-directed corrections for disturbances to the limb or behavioral goal. The primary motor cortex (M1) is a key region involved in processing feedback for rapid motor corrections, yet we know little about how M1 circuits are recruited by different sources of sensory feedback to make rapid corrections. We trained two male monkeys (Macaca mulatta) to make goal-directed reaches and on random trials introduced different sensory errors by either jumping the visual location of the goal (goal jump), jumping the visual location of the hand (cursor jump), or applying a mechanical load to displace the hand (proprioceptive feedback). Sensory perturbations evoked a broad response in M1 with ∼73% of neurons (n = 257) responding to at least one of the sensory perturbations. Feedback responses were also similar as response ranges between the goal and cursor jumps were highly correlated (range of r = [0.91, 0.97]) as were the response ranges between the mechanical loads and the visual perturbations (range of r = [0.68, 0.86]). Lastly, we identified the neural subspace each perturbation response resided in and found a strong overlap between the two visual perturbations (range of overlap index, 0.73-0.89) and between the mechanical loads and visual perturbations (range of overlap index, 0.36-0.47) indicating each perturbation evoked similar structure of activity at the population level. Collectively, our results indicate rapid responses to errors from different sensory sources target similar overlapping circuits in M1.

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.

Convergent MAPK pathway alterations mediate acquired resistance to FGFR inhibitors in FGFR2 fusion-positive cholangiocarcinoma.

BACKGROUND & AIMS: There is a knowledge gap in understanding mechanisms of resistance to fibroblast growth factor receptor (FGFR) inhibitors (FGFRi) and a need for novel therapeutic strategies to overcome it. We investigated mechanisms of acquired resistance to FGFRi in patients with FGFR2-fusion-positive cholangiocarcinoma (CCA). METHODS: A retrospective analysis of patients who received FGFRi therapy and underwent tumor and/or cell-free DNA analysis, before and after treatment, was performed. Longitudinal circulating tumor DNA samples from a cohort of patients in the phase I trial of futibatinib (NCT02052778) were assessed. FGFR2-BICC1 fusion cell lines were developed and secondary acquired resistance mutations in the mitogen-activated protein kinase (MAPK) pathway were introduced to assess their effect on sensitivity to FGFRi in vitro. RESULTS: On retrospective analysis of 17 patients with repeat sequencing following FGFRi treatment, new FGFR2 mutations were detected in 11 (64.7%) and new alterations in MAPK pathway genes in nine (52.9%) patients, with seven (41.2%) patients developing new alterations in both the FGFR2 and MAPK pathways. In serially collected plasma samples, a patient treated with an irreversible FGFRi tested positive for previously undetected BRAF V600E, NRAS Q61K, NRAS G12C, NRAS G13D and KRAS G12K mutations upon progression. Introduction of a FGFR2-BICC1 fusion into biliary tract cells in vitro sensitized the cells to FGFRi, while concomitant KRAS G12D or BRAF V600E conferred resistance. MEK inhibition was synergistic with FGFRi in vitro. In an in vivo animal model, the combination had antitumor activity in FGFR2 fusions but was not able to overcome KRAS-mediated FGFRi resistance. CONCLUSIONS: These findings suggest convergent genomic evolution in the MAPK pathway may be a potential mechanism of acquired resistance to FGFRi. CLINICAL TRIAL NUMBER: NCT02052778. IMPACT AND IMPLICATIONS: We evaluated tumors and plasma from patients who previously received inhibitors of fibroblast growth factor receptor (FGFR), an important receptor that plays a role in cancer cell growth, especially in tumors with abnormalities in this gene, such as FGFR fusions, where the FGFR gene is fused to another gene, leading to activation of cancer cell growth. We found that patients treated with FGFR inhibitors may develop mutations in other genes such as KRAS, and this can confer resistance to FGFR inhibitors. These findings have several implications for patients with FGFR2 fusion-positive tumors and provide mechanistic insight into emerging MAPK pathway alterations which may serve as a therapeutic vulnerability in the setting of acquired resistance to FGFRi.

Rapid white matter changes in children with conduct problems during a parenting intervention.

Studies report that the microstructural integrity of the uncinate fasciculus (UF; connecting the anterior temporal lobe to the orbitofrontal cortex) is abnormal in adults with psychopathy and children with conduct problems (CP), especially those with high callous-unemotional (CU) traits. However, it is unknown if these abnormalities are 'fixed' or 'reversible'. Therefore, we tested the hypothesis that a reduction in CP symptoms, following a parenting intervention, would be associated with altered microstructural integrity in the UF. Using diffusion tensor imaging tractography we studied microstructural differences (mean diffusivity (MD) and radial diffusivity (RD)) in the UF of 43 typically developing (TD) and 67 boys with CP before and after a 14-week parenting intervention. We also assessed whether clinical response in CP symptoms or CU traits explained changes in microstructure following the intervention. Prior to intervention, measures of MD and RD in the UF were increased in CP compared to TD boys. Following intervention, we found that the CP group had a significant reduction in RD and MD. Further, these microstructural changes were driven by the group of children whose CU traits improved (but not CP symptoms as hypothesized). No significant microstructural changes were observed in the TD group. Our findings suggest, for the first time, that microstructural abnormalities in the brains of children with CP may be reversible following parenting intervention.

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer.

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (> 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib.

A robot-based interception task to quantify upper limb impairments in proprioceptive and visual feedback after stroke.

BACKGROUND: A key motor skill is the ability to rapidly interact with our dynamic environment. Humans can generate goal-directed motor actions in response to sensory stimulus within ~ 60-200ms. This ability can be impaired after stroke, but most clinical tools lack any measures of rapid feedback processing. Reaching tasks have been used as a framework to quantify impairments in generating motor corrections for individuals with stroke. However, reaching may be inadequate as an assessment tool as repeated reaching can be fatiguing for individuals with stroke. Further, reaching requires many trials to be completed including trials with and without disturbances, and thus, exacerbate fatigue. Here, we describe a novel robotic task to quantify rapid feedback processing in healthy controls and compare this performance with individuals with stroke to (more) efficiently identify impairments in rapid feedback processing. METHODS: We assessed a cohort of healthy controls (n = 135) and individuals with stroke (n = 40; Mean 41 days from stroke) in the Fast Feedback Interception Task (FFIT) using the Kinarm Exoskeleton robot. Participants were instructed to intercept a circular white target moving towards them with their hand represented as a virtual paddle. On some trials, the arm could be physically perturbed, the target or paddle could abruptly change location, or the target could change colour requiring the individual to now avoid the target. RESULTS: Most participants with stroke were impaired in reaction time (85%) and end-point accuracy (83%) in at least one of the task conditions, most commonly with target or paddle shifts. Of note, this impairment was also evident in most individuals with stroke when performing the task using their unaffected arm (75%). Comparison with upper limb clinical measures identified moderate correlations with the FFIT. CONCLUSION: The FFIT was able to identify a high proportion of individuals with stroke as impaired in rapid feedback processing using either the affected or unaffected arms. The task allows many different types of feedback responses to be efficiently assessed in a short amount of time.

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.

I Know What to Do; I Can Do It; It Will Work: The Brief Parental Self Efficacy Scale (BPSES) for Parenting Interventions.

Parental self-efficacy predicts outcomes for parenting interventions for child behaviour problems, but there is a need for a brief measure that can be repeated over treatment and applies to a wide age range. The present study describes the development of such a measure, the Brief Parental Self-Efficacy Scale (BPSES). The psychometrics of the BPSES is presented across a wide age range from preschool to late adolescent in a sample comprised of four different intervention contexts. Evidence for structural validity, internal consistency, content validity, configural measurement invariance (equivalent factor structure) and test-retest reliability is presented alongside convergent validity against measures of parental self-efficacy, child behaviour problems, as well as self-report and observed parenting styles. Finally, lower levels of BPSES at baseline predicted increased disengagement from an intensive, individualised family therapy intervention for antisocial youth, while higher baseline levels predicted increased response to a group parenting programme for primary school aged children. The BPSES shows promise as a measure that can be used across a wide age-range, for a variety of parenting interventions for disruptive behaviour problems and which is sufficiently brief to be used as a routine outcome measurement during treatment.

Neurological Impairment in Critically Ill Patients on Dialysis: Research Letter for the INCOGNITO-AKI Feasibility Study.

Background: Acute kidney injury (AKI) resulting in kidney replacement therapy is rising among critically ill adults. Long-term kidney replacement therapy and critical illness are independently linked to acute and prolonged cognitive impairment, and structural brain pathology. Poor regional cerebral oxygenation (rSO2) may be a contributing factor. Objective: To assess the feasibility of testing the association between intradialytic rSO2 and acute and long-term neurological outcomes. Design: Longitudinal observational study. Setting and Participants: We enrolled patients initiating continuous kidney replacement therapy or intermittent hemodialysis in the Kingston Health Sciences Centre (KHSC) Intensive Care Unit (ICU). Measurements and Methods: rSO2 was monitored during the first 72 hours of continuous kidney replacement therapy or throughout each intermittent hemodialysis session. We measured acute neurological impairment by daily delirium screening and long-term neurocognitive outcomes using the Kinarm robot, Repeatable Battery for the Assessment of Neuropsychological Status, and brain magnetic resonance imaging. Results: Of 484 ICU patients, 26 met the screening criteria. Two declined, and 13 met at least one exclusion criteria. Eleven patients were enrolled. Eight died in ICU, one died 2 months after discharge, and one declined follow-up. Data capture rates were high: rSO2/vitals (91.3%), and delirium screening and demographics (100%). Longitudinal testing was completed in 50% (1 of 2) of survivors. Limitations: Enrollment was low due to a variety of factors, limiting our ability to evaluate long-term outcomes. Conclusion: rSO2 and delirium data collection is feasible in critically ill patients undergoing kidney replacement therapy; high mortality limits follow-up.

Contexte: L'insuffisance rénale aiguë (IRA) menant à une thérapie de remplacement rénal est en augmentation chez les adultes aux soins intensifs. Un séjour aux soins intensifs et la thérapie de remplacement rénal à long terme sont indépendamment liés à des déficits cognitifs aigus et prolongés ainsi qu'à des pathologies structurelles du cerveau. La faible saturation régionale du cerveau en oxygène (rSO2) pourrait être un facteur contributif. Objectif: Évaluer la possibilité de tester l'association entre la rSO2 intradialytique et les résultats neurologiques aigus et chroniques. Type d'étude: Étude observationnelle longitudinale. Cadre et sujets de l'étude: Nous avons recruté des patients qui entamaient une thérapie de remplacement rénal en continu ou une hémodialyse intermittente à l'unité des soins intensifs (USI) du Kingston Health Sciences Centre (KHSC). Mesures et méthodologie: La rSO2 a été surveillée pendant les 72 premières heures de thérapie de remplacement rénal en continu, ou tout au long de chaque séance d'hémodialyse intermittente. Nous avons mesuré les déficits neurologiques aigus par un dépistage quotidien du délirium et les atteintes neurocognitives à long terme à l'aide du robot Kinarm, de la Repeatable Battery for the Assessment of Neuropsychological Status et de l'imagerie par résonance magnétique cérébrale. Résultats: Sur les 484 patients hospitalisés à l'USI, 26 répondaient aux critères de sélection. Deux ont refusé de participer à l'étude et treize satisfaisaient à au moins un critère d'exclusion. Onze patients ont été inclus à l'étude. Huit patients sont décédés à l'USI, un est décédé deux mois après sa sortie de l'hôpital et un a refusé le suivi. Les taux de saisie des données étaient élevés: rSO2 et paramètres vitaux (91,3 %), dépistage du délirium et démographie (100 %). Des tests longitudinaux ont été effectués chez 50 % (1 de 2) des survivants. Limites: Le taux d'inscription était faible en raison de divers facteurs, ce qui a limité notre capacité à évaluer les résultats à long terme. Conclusion: Il est possible de collecter des données sur la rSO2 et le délirium chez les patients de soins intensifs qui suivent une thérapie de remplacement rénal; un taux de mortalité élevé a limité le suivi. Trial Registration: clinicaltrials.gov, registration number NCT04722939.

Impairments of the ipsilesional upper-extremity in the first 6-months post-stroke.

BACKGROUND: Ipsilesional motor impairments of the arm are common after stroke. Previous studies have suggested that severity of contralesional arm impairment and/or hemisphere of lesion may predict the severity of ipsilesional arm impairments. Historically, these impairments have been assessed using clinical scales, which are less sensitive than robot-based measures of sensorimotor performance. Therefore, the objective of this study was to characterize progression of ipsilesional arm motor impairments using a robot-based assessment of motor function over the first 6-months post-stroke and quantify their relationship to (1) contralesional arm impairment severity and (2) stroke-lesioned hemisphere. METHODS: A total of 106 participants with first-time, unilateral stroke completed a unilateral assessment of arm motor impairment (visually guided reaching task) using the Kinarm Exoskeleton. Participants completed the assessment along with a battery of clinical measures with both ipsilesional and contralesional arms at 1-, 6-, 12-, and 26-weeks post-stroke. RESULTS: Robotic assessment of arm motor function revealed a higher incidence of ipsilesional arm impairment than clinical measures immediately post-stroke. The incidence of ipsilesional arm impairments decreased from 47 to 14% across the study period. Kolmogorov-Smirnov tests revealed that ipsilesional arm impairment severity, as measured by our task, was not related to which hemisphere was lesioned. The severity of ipsilesional arm impairments was variable but displayed moderate significant relationships to contralesional arm impairment severity with some robot-based parameters. CONCLUSIONS: Ipsilesional arm impairments were variable. They displayed relationships of varying strength with contralesional impairments and were not well predicted by lesioned hemisphere. With standard clinical care, 86% of ipsilesional impairments recovered by 6-months post-stroke.

Informed consent practices in clinical research: present and future.

Clinical research must balance the need for ambitious recruitment with protecting participants' autonomy; a requirement of which is informed consent. Despite efforts to improve the informed consent process, participants are seldom provided sufficient information regarding research, hindering their ability to make informed decisions. These issues are particularly pervasive among patients experiencing acute illness or neurological impairment, both of which may impede their capacity to provide consent. There is a critical need to understand the components, requirements, and methods of obtaining true informed consent to achieve the vast numbers required for meaningful research. This paper provides a comprehensive review of the tenets underlying informed consent in research, including the assessment of capacity to consent, considerations for patients unable to consent, when to seek consent from substitute decision-makers, and consent under special circumstances. Various methods for obtaining informed consent are addressed, along with strategies for balancing recruitment and consent.

Transcranial magnetic stimulation in non-human primates: A systematic review.

Transcranial magnetic stimulation (TMS) is widely employed as a tool to investigate and treat brain diseases. However, little is known about the direct effects of TMS on the brain. Non-human primates (NHPs) are a valuable translational model to investigate how TMS affects brain circuits given their neurophysiological similarity with humans and their capacity to perform complex tasks that approach human behavior. This systematic review aimed to identify studies using TMS in NHPs as well as to assess their methodological quality through a modified reference checklist. The results show high heterogeneity and superficiality in the studies regarding the report of the TMS parameters, which have not improved over the years. This checklist can be used for future TMS studies with NHPs to ensure transparency and critical appraisal. The use of the checklist would improve methodological soundness and interpretation of the studies, facilitating the translation of the findings to humans. The review also discusses how advancements in the field can elucidate the effects of TMS in the brain.

Clinical, Neuroimaging and Robotic Measures Predict Long-Term Proprioceptive Impairments following Stroke.

Proprioceptive impairments occur in ~50% of stroke survivors, with 20-40% still impaired six months post-stroke. Early identification of those likely to have persistent impairments is key to personalizing rehabilitation strategies and reducing long-term proprioceptive impairments. In this study, clinical, neuroimaging and robotic measures were used to predict proprioceptive impairments at six months post-stroke on a robotic assessment of proprioception. Clinical assessments, neuroimaging, and a robotic arm position matching (APM) task were performed for 133 stroke participants two weeks post-stroke (12.4 ± 8.4 days). The APM task was also performed six months post-stroke (191.2 ± 18.0 days). Robotics allow more precise measurements of proprioception than clinical assessments. Consequently, an overall APM Task Score was used as ground truth to classify proprioceptive impairments at six months post-stroke. Other APM performance parameters from the two-week assessment were used as predictive features. Clinical assessments included the Thumb Localisation Test (TLT), Behavioural Inattention Test (BIT), Functional Independence Measure (FIM) and demographic information (age, sex and affected arm). Logistic regression classifiers were trained to predict proprioceptive impairments at six months post-stroke using data collected two weeks post-stroke. Models containing robotic features, either alone or in conjunction with clinical and neuroimaging features, had a greater area under the curve (AUC) and lower Akaike Information Criterion (AIC) than models which only contained clinical or neuroimaging features. All models performed similarly with regard to accuracy and F1-score (>70% accuracy). Robotic features were also among the most important when all features were combined into a single model. Predicting long-term proprioceptive impairments, using data collected as early as two weeks post-stroke, is feasible. Identifying those at risk of long-term impairments is an important step towards improving proprioceptive rehabilitation after a stroke.

Caregiver goals and satisfaction for menstrual suppression in adolescent females with developmental disabilities: A prospective cohort study.

BACKGROUND: Adolescents with developmental disabilities and their caregivers often seek menstrual management. Caregivers frequently serve as medical decision-makers, and little is known about caregiver goals for menstrual management and satisfaction over time. OBJECTIVE: Assess caregiver reasons for initiating menstrual management in adolescents with disabilities and satisfaction over 12 months. METHODS: Prospective cohort study of caregivers of adolescents with developmental disabilities seeking menstrual management at a pediatric and adolescent gynecology clinic. Data derive from caregiver surveys and adolescents' electronic medical records. RESULTS: Ninety-two caregiver-adolescent pairs enrolled. The mean age of adolescents was 14.4 (±2.6). The most common method started was levonorgestrel intrauterine device (LNG-IUD; 52, 56.5%), followed by oral norethindrone acetate (21, 22.8%). Caregivers cited hygiene concerns (84.8%), behavioral problems (52.2%), and heavy/excessive bleeding (48.9%) as reasons for initiating menstrual suppression. Caregivers who identified hygiene or heavy/excessive bleeding as the most important reason for management were more likely to select LNG-IUD (p = 0.009). Caregivers who cited behavioral/mood or seizure concerns as the most important reason were more likely to choose other methods (p < 0.05). At 12 months, caregiver satisfaction with all methods was high (66.2-86.9 on a 100-point scale). For every additional day of bleeding, satisfaction decreased by 3.7 points (95% CI: 2.3-5.0). CONCLUSIONS: Caregiver satisfaction with all methods is high; however, it negatively correlates with days of bleeding. Caregiver reasons for menstrual suppression influence the method chosen. Management may reflect both patient and caregiver priorities; research is needed to better understand shared decision-making models that promote reproductive autonomy in adolescents with a developmental disability.

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.

Impairments of the arm and hand are highly correlated during subacute stroke.

BACKGROUND: The classical description of poststroke upper limb impairment follows a proximalto-distal impairment gradient. Previous studies are equivocal on whether the hand is more impaired than the arm. OBJECTIVE: To compare impairment of the arm and hand during subacute stroke. METHOD: A total of 73 individuals were evaluated for impairment of the upper limb within 30 days (early subacute) and within 90-150 days (late subacute) of stroke. Impairments were quantified using the Chedoke-McMaster Stroke Assessment (CMSA) for the arm and hand, Purdue Pegboard task, and a robotic Visually Guided Reaching task. RESULTS: In the early phase 42% of participants in the early phase and 59% in the late phase received the same CMSA score for the arm and hand, with 88% and 95% of participants in the early and late phases, respectively, receiving a 1-point difference. Strong correlations exist between the CMSA arm and hand scores (early r = 0.79, late r = 0.75), and moderate - strong correlations exist between CMSA arm and hand scores and Purdue Pegboard and Visually Guided Reaching performances (r = 0.66-0.81). No systematic differences were found between the arm and hand. CONCLUSION: Impairments in the arm and hand during subacute stroke are highly correlated and do not support the presence of a proximal-to-distal gradient.

Personalised interventions for subgroups of children with conduct problems.

BACKGROUND: Conduct problems are a range of disruptive behaviours in childhood that are associated with long-term adverse outcomes in adolescence and adulthood, including antisocial behaviour, substance misuse, and poor academic achievement. Children with conduct problems can vary according to age of onset, comorbidities, and environmental factors, and it has been suggested that certain groups of children may have different treatment outcomes. Therefore, it is important to assess the extent to which personalised interventions for different groups of children with conduct problems may affect outcomes. To our knowledge, this is the first review to systematically identify and appraise the effectiveness of personalised interventions, adapted, or developed, for prespecified subgroups of children with conduct problems. OBJECTIVES: To assess whether personalised interventions, adapted or developed for subgroups of children with conduct problems are effective in improving outcomes. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was 1 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs), in any setting, in children (aged two to 12 years) with conduct problems and within a prespecified subgroup, comparing a personalised intervention with a non-personalised intervention, waitlist control, or treatment as usual. Personalised interventions included adaptations to standard practice, such as parent-training programmes; other recommended interventions for children with conduct problems; or interventions developed specifically to target subgroups of children with conduct problems. We excluded non-personalised and non-psychological interventions (e.g. pharmacological or dietary intervention). Prespecified subgroups of children with conduct problems, however defined, were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. child conduct problems or disruptive behaviour and 2. ADVERSE EVENTS: Our secondary outcomes were 3. personalised treatment outcomes relevant to each subgroup, 4. parenting skills and knowledge, 5. family functioning, engagement and decreased dropout, and 6. educational outcomes. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We identified 13 RCTs (858 participants). Seven studies were conducted in the USA, five in Australia, and one in Germany. Eleven studies reported their source of funding, with five studies receiving grants from the National Institute of Mental Health. In total, 15 different funders supported the studies included in the review. We separated subgroups of children with conduct problems into three broad categories: children with co-occurring conditions (e.g. emotional difficulties), parent characteristics (e.g. conflict between parents), or familial/environmental circumstances (e.g. rural families). All studies delivered a personalised intervention that was adapted or developed for a prespecified subgroup of children with conduct problems. We rated all trials at unclear or high risk of bias in most domains. Below, we report the results of improvement in child conduct problems and disruptive behaviour, personalised treatment outcomes, and parenting skills and knowledge for our main comparison: personalised versus non-personalised interventions. Improvement in child conduct problems and disruptive behaviour Compared with a non-personalised intervention, a personalised intervention may result in a slight improvement in child conduct problems or disruptive behaviour measured using the Eyberg Child Behavior Inventory (ECBI) Problem subscale in the short term (mean difference (MD) -3.04, 95% confidence interval (CI) -6.06 to -0.02; 6 studies, 278 participants; P = 0.05), but may have little to no effect on improving child conduct problems or disruptive behaviour measured by the ECBI Intensity subscale (MD -6.25, 95% CI -16.66 to 4.15; 6 studies, 278 participants; P = 0.24), or the Externalising subscale of the Child Behaviour Checklist (CBCL) (MD -2.19, 95% CI -6.97 to 2.59; 3 studies, 189 participants, P = 0.37) in the short term. We graded the certainty of evidence as very low for all three outcomes, meaning any estimate of effect is very uncertain.  Personalised treatment outcomes, relevant to each subgroup Although six studies reported personalised treatment outcomes, relevant to each subgroup, we were unable to pool the data due to differences between the measures used in the studies and the heterogeneity this would produce in analysis. The results for this outcome were inconclusive. Parenting skills and knowledge Although seven studies reported parenting skills and knowledge, we were unable to pool the data due to differences between the measures used in the studies and the heterogeneity this would produce in analysis. The results for this outcome were inconclusive.  Adverse events None of the trials reported monitoring adverse events. Summary of results In summary, there is limited evidence that personalised intervention improves child conduct problems, personalised treatment outcomes, relevant to each subgroup, or parenting skills and knowledge compared with a non-personalised intervention. AUTHORS' CONCLUSIONS: There is limited evidence for the effectiveness of personalised interventions for subgroups of children with conduct problems. The certainty of evidence for all outcomes was very low, meaning that we have very little confidence in the estimated effects and the true effects may be different to our findings, which will limit the relevance of our findings to clinical decisions. To overcome the limitations of the evidence, large-scale RCTs are needed to determine whether personalised interventions, adapted or developed, for subgroups of children with conduct problems are effective in improving outcomes. Consensus on the most appropriate measures to use in these studies is needed in order to facilitate cross-study comparisons. Persistent conduct problems predict a range of adverse long-term outcomes, so future research should investigate the medium- and long-term effects of personalised treatments. Studies are needed in low- and middle-income countries as well as studies recruiting children aged between nine and 12 years, as they were under-represented in the studies.