Prehospital Tranexamic Acid in Major Pediatric Trauma Within a Physician-Led Emergency Medical Services System: A Multicenter Retrospective Study.

OBJECTIVES: Describe prehospital tranexamic acid (TXA) use and appropriateness within a major trauma pediatric population, and identify the factors associated with its use. DESIGN: Multicenter, retrospective study, 2014-2020. SETTING: Data were extracted from a multicenter French trauma registry including nine trauma centers within a physician-led prehospital emergency medical services (EMS) system. PATIENTS: Patients less than 18 years old were included. Those who did not receive prehospital intervention by a mobile medical team and those with missing data on TXA administration were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nine-hundred thirty-four patients (median [interquartile range] age: 14 yr [9-16 yr]) were included, and 68.6% n = 639) were male. Most patients were involved in a road collision (70.2%, n = 656) and suffered a blunt trauma (96.5%; n = 900). Patients receiving TXA (36.6%; n = 342) were older (15 [13-17] vs 12 yr [6-16 yr]) compared with those who did not. Patient severity was higher in the TXA group (Injury Severity Score 14 [9-25] vs 6 [2-13]; p < 0.001). The median dosage was 16 mg/kg (13-19 mg/kg). TXA administration was found in 51.8% cases ( n = 256) among patients with criteria for appropriate use. Conversely, 32.4% of patients ( n = 11) with an isolated severe traumatic brain injury (TBI) also received TXA. Age (odds ratio [OR], 1.2; 95% CI, 1.1-1.2), A and B prehospital severity grade (OR, 7.1; 95% CI, 4.1-12.3 and OR, 4.5; 95% CI, 2.9-6.9 respectively), and year of inclusion (OR, 1.2; 95% CI, 1.1-1.3) were associated with prehospital TXA administration. CONCLUSIONS: In our physician-led prehospital EMS system, TXA is used in a third of severely injured children despite the lack of high-level of evidence. Only half of the population with greater than or equal to one criteria for appropriate TXA use received it. Conversely, TXA was administered in a third of isolated severe TBI. Further research is warranted to clarify TXA indications and to evaluate its impact on mortality and its safety profile to oversee its prescription.

Fibrinolytic shutdown diagnosed with rotational thromboelastometry represents a moderate form of coagulopathy associated with transfusion requirement and mortality: A retrospective analysis.

BACKGROUND: Viscoelastic techniques have made it possible to describe specific fibrinolytic phenotypes (physiological, hyperfibrinolysis and shutdown) and to establish a relationship of these phenotypes with outcome. However, there remains a debate as to whether shutdown is a state of hypercoagulability or rather a coagulopathy with moderate fibrinolysis and fibrinogen consumption. OBJECTIVES: Our objectives were to describe the relationship between fibrinolytic phenotypes and outcomes, and to report the effects of tranexamic acid (TXA) administration. DESIGN: This was a retrospective analysis of prospectively acquired data from a trauma registry. SETTING: An academic level 1 trauma centre in the Lyon Region, from March 2011 to December 2016. PATIENTS: We included all injured patients who had a rotational thromboelastometry analysis at admission. Fibrinolytic phenotypes were determined according to the maximum lysis: shutdown less than 3%, physiological 3 to 15%, hyperfibrinolysis more than 15%. MAIN OUTCOME MEASURE: Mortality at 24 h and at hospital discharge. RESULTS: During the study period, 473 patients were included with the following phenotypes: physiological (344 patients, 73%), shutdown (107 patients, 23%) and hyperfibrinolysis (22 patients, 5%). There was an increase in injury severity, prothrombin time ratio, fibrin degradation products and transfusion requirements from the physiological to the shutdown and hyperfibrinolysis phenotypes. Prehospital TXA administration increased the rate of shutdown and decreased the maximum lysis value at admission. After adjustment, multivariate analysis showed that fibrinolytic phenotypes, but not TXA, were independently associated with an increased risk of early death and death before hospital discharge: shutdown [odds ratio (95% confidence interval)] 2.4 (1.2 to 4.8) and hyperfibrinolysis 67.9 (7.4 to 624.2). CONCLUSION: The results of the current study suggest that shutdown, which is associated with injury severity and mortality, probably reflects a moderate form of coagulopathy and fibrinolysis rather than a hypercoagulopathy. Therefore, the observation of shutdown fibrinolysis on thromboelastography/rotational thromboelastometry should not lead to withholding but rather to the administration of TXA.

Disentangling Tourette syndrome heterogeneity through hierarchical ascendant clustering.

AIM: To explore the heterogeneity of Tourette syndrome as part of a neurodevelopmental spectrum. METHOD: Using hierarchical ascendant clustering based on tic symptoms, developmental milestones, and neurodevelopmental comorbidities, we analyzed the heterogeneity of Tourette syndrome phenotypes in a sample of 174 children and adolescents with Tourette syndrome referred to a tertiary university clinic. RESULTS: The model yielded three distinct clusters characterized as follows. In cluster 1, we found many neurodevelopmental comorbidities (including intellectual disabilities, autism spectrum disorder, attention-deficit-hyperactivity disorder [ADHD], and learning disabilities) and academic impairments. In cluster 2, patients had no other neurodevelopmental comorbidities. In cluster 3, patients had higher intelligence, a high frequency of attentional impairment, school problems related to both ADHD and unspecific attention difficulties, and handwriting problems related to the tics themselves. Interestingly, clusters did not differ in terms of family history or anxious-depressive comorbidities. The only other differences that emerged were related to prenatal or perinatal risk factors (more represented in cluster 1) and treatment profiles (higher rates of stimulants in cluster 1). INTERPRETATION: We conclude that from a phenotypical perspective, Tourette syndrome is a heterogeneous syndrome with at least three main clusters that may help in addressing the etiological basis of Tourette syndrome and specific rehabilitative and therapeutic approaches. WHAT THIS PAPER ADDS: The clustering of Tourette syndrome based on comorbidity with other neurodevelopmental conditions reveals three clusters. A group of patients with Tourette syndrome show school difficulties related to non-specific attention and writing problems. Analysing only children and adolescents helps to distinguish between developmental comorbid conditions and coexistent disorders.

From child-peer similarity in imitative behavior to matched peer-mediated interventions in autism.

Self-consciousness develops through a long process, from pre-reflexive consciousness relying on body perception, to "meta" self-awareness. It emerges from the imitative experience between children and their peers. This experience linked to the capacity to test structural similarities between oneself and others, is addressed according to the concept of interpersonal affordance. We hypothesize that the opportunity for co-actors to engage in a process of interpersonal coordination is underlined by their similarity in terms of morphological, behavioral and motor features. This experience can sustain the emergence of new affordances for objects for each co-actor, as well as new affordances in terms of joint actions. We apply this idea in the context of peer-mediated interventions (PMI) in autism spectrum disorder (ASD). We argue that, in PMI, an encounter between children with autism and similar peers would foster the opportunity to engage in a spontaneous process of interpersonal coordination. This process would enable the development of self-consciousness and the emergence of perception of interpersonal, self and other's affordances for children with autism. We conclude that metrics to assess morphological, behavioral and motor similarity should then be defined and used in future studies to test our hypothesis in children with autism versus TD children or between children with autism.

Neuro damage control: current concept and civilian applications.

Damage control (DC) initially referred to abbreviated (<1 h) surgical procedures to control abdominal hemorrhage in severe trauma patients, to avoid the 'bloody vicious circle' of hypothermia-coagulopathy-acidosis-hypocalcemia. Progressively, the concept was extended to pre-hospital and peri-operative surgical and non-surgical trauma care. The DC strategy can be applied either in a single severe trauma patient at risk of progression toward the bloody vicious circle or in case of limited or overwhelmed health resources (deprived environment, mass casualties, etc.). DC strategies in neurological casualties have improved over the last decade in military neurosurgeons, but remain poorly codified in civilian settings. In this comprehensive review, we summarize the current concept of neuro-DC, which includes surgical and medical care for neurological injuries as part of a DC strategy. Neuro-DC basically consists in: (i) preventing secondary brain injury; (ii) controlling intracranial bleeding; (iii) controlling intracranial pressure; (iv) limiting contamination of compound wounds; and (v) achieving secondary anatomical restoration.

Motor Skill Improvement Using Compressive Garments in a Child with Multidimensional Impairments and Ehlers-Danlos Syndrome.

We report the case of an 8-year-old child with a complex neurodevelopmental disorder, including severe developmental coordination disorder with dysgraphia, anxiety and depression, mild social functioning impairments, headache and chronic musculoskeletal pain, secondary to Ehlers-Danlos syndrome (EDS) hypermobility type. We explored whether wearing whole-body compressive garments (CGs) could improve his motor skills assessed through standardized and experimental procedures. In addition to the effectiveness of CGs on pain, we found partial improvements in his motor skills, specifically postural control, hand movements, and body schema representation, after wearing CGs for 15 days. During an experimental motor imitation task with a virtual tightrope walker, we found improvements in interpersonal synchronization with performances closer to those of typical developing (TD) controls. We conclude that CGs appear to be an innovative and interesting adjuvant treatment for motor skill impairments in children with multidimensional impairments involving EDS. These promising results require confirmation by further evidence-based research.

Which injured patients with moderate fibrinogen deficit need fibrinogen supplementation?

BACKGROUND: In severely injured patients, fibrinogen supplementation is recommended when fibrinogenemia is < 1.5 g L-1, but some teams have suggested to use higher thresholds (fibrinogenemia < 2.0 g L-1 or FIBTEM clot amplitude at 5 min (A5) values < 11 mm). The goal of this study was to specify in patients with a moderate fibrinogen deficit (MFD) whether some admission characteristics would be associated with fibrinogen administration at 24 h. METHODS: Prospective analysis of retrospectively collected data from a trauma registry (01/2011-12/2019). MFD-C was defined by a fibrinogenemia 1.51-1.99 g L-1 or the corresponding FIBTEM-A5 values (MFD-A5) that were determined from linear regression and ROC curve analysis. Administration of fibrinogen were described according to the following admission parameters: shock index (SI) > 1, hemoglobin level < 110 g L-1 (HemoCue®), and base deficit > 5 mEq L-1. Data are expressed as count (%), median [IQR]. RESULTS: 1076 patients were included in the study and 266 (27%) had MFD-C, among them, 122/266 (46%) received fibrinogen. Patients with MFD-C who received fibrinogen were more severely injured (ISS: 27 [19-36] vs. 24 [17-29]) and had more impaired vital signs (base deficit: 5.4 [3.6-7.8] vs. 3.8 [2.0-6.0]). Linear regression analysis found a positive correlation between fibrinogen level and FIBTEM-A5 (r: 0.805). For a fibrinogen level < 1.5 g L-1 and < 2.0 g L-1, FIBTEM-A5 thresholds were 6 mm (sensitivity 85%, specificity 83%, AUC: 0.934) and 9 mm (sensitivity 84%, specificity 69%, AUC: 0.874), respectively. MFD-A5 values (185 (27%) patients) were defined as a FIBTEM-A5 between 7 and 9 mm. More than 50% of MFD-C patients presenting a SI > 1, a hemoglobin level < 110 g L-1, or a base deficit > 5.0 mEq L-1 received fibrinogen. The relative risk [95% CI] for fibrinogen administration (SI > 1) were 1.39 [1.06-1.82] for MFD-C, and 2.17 [1.48-3.19] for MFD-A5. Results were not modified after adjustment on the ISS. CONCLUSIONS: We have shown in this study an association between shock parameters and fibrinogen administration. Further studies are needed to determine how these parameters may be used to guide fibrinogen administration in trauma patients with MFD.

[School refusal]. / Refus scolaire.

School refusal. School refusal covers a very heterogeneous set of problems ranging from refusal of schooling - in terms of engagement in learning or in situations of evaluation, in relation to knowledge - to school phobia or anxious school refusal. Furthermore, the clinical form of children and adolescents refusing school is determined by a wide range of factors - individual, family, school and cultural - that interact with each other and change over time. In the context of a multidimensional approach, the apprehension of school refusal involves a dialogue between the family, health professionals and the various players in national education. This approach makes it possible to think about the developmental trajectory of the child and lead to the establishment of a personalized care project.

Refus scolaire. Le refus scolaire recouvre un ensemble très hétérogène de problématiques allant du refus de la scolarité ­ en termes d'engagement dans les apprentissages ou dans les situations d'évaluation, de rapport au savoir ­ à la phobie scolaire ou refus scolaire anxieux. De plus, le tableau clinique des enfants et adolescents refusant l'école est déterminé par un large éventail de facteurs ­ individuels, familiaux, scolaires et culturels ­ qui interagissent entre eux et se modifient au fil du temps. Dans le cadre d'une approche pluridimensionnelle, l'appréhension du refus scolaire implique un dialogue entre la famille, les professionnels de santé et les différents acteurs de l'Éducation nationale. Cette démarche permet de penser la trajectoire développementale de l'enfant et d'aboutir à la mise en place d'un projet de soins personnalisé.

Multidimensional impairments.

Children and adolescents with neurodevelopmental disorders often show complex developmental disorders, including multiple areas of dysfunction such as emotional regulation and behavior, school integration, and learning difficulties. These multidimensionally impaired children share some common features with children with autism spectrum disorders (ASDs). However, paradoxically, they could qualify as diagnostically homeless. Several proposals have been formulated to categorize subgroups of these children, whose diversity and overlap in clinical expression emphasize the importance of using a multidimensional assessment inscribed in a developmental perspective. Here, we review these different classification proposals and describe a multidimensional approach that, in addition to a categorical approach, could constitute a complementary point of view. We believe that this multidimensional perspective allows one to address the child holistically, taking into account his or her interactive experience with the environment, and achieve a functional diagnosis enabling the elaboration of a tailored therapeutic plan and better school inclusion.

Developmental and symptom profiles in early-onset psychosis.

Psychotic disorders in children are more heterogeneous than is captured by categorical diagnoses. In a new cohort of children and adolescents, we evaluated the relationships among age at onset (AAO), clinical symptoms and developmental impairments. Patients with schizophrenia and other "spectrum" psychotic diagnoses (N = 88; AAO 6-17, mean 12.6) were evaluated with diagnostic interviews, a new clinical scale (Lifetime Dimensions of Psychosis Scale-Child and Adolescent), and neuropsychological and medical evaluations. Key findings were replicated in an adult cohort of 2420 cases, including 127 with retrospective AAO<13. Factor and cluster analyses were carried out to identify clinical profiles. Five clinical factors were identified in each cohort: Positive, Bizarre Positive, Negative/Formal Thought Disorder, Depression and Mania. Earlier AAO predicted severity of bizarre positive symptoms in children and of bizarre and other symptoms in adults. Four clinical clusters in the child cohort were characterized by: more severe bizarre positive symptoms (N = 31); negative symptoms (N = 15); premorbid autism spectrum features and developmental delay (N = 12); and depressive symptoms with heterogeneous diagnoses and mild positive/negative symptoms (N = 25). Previous factor-analytic studies of childhood psychosis did not specifically consider bizarre positive symptoms. Here, bizarre positive symptoms emerged as clinical markers of severe, childhood-onset psychosis similar to adult schizophrenia. The four clusters are clinically meaningful and useful for treatment planning and potentially for biological research. Childhood-onset cases are rare and thus difficult to study, but additional, larger cohorts may be useful in dissecting the biological and developmental heterogeneity of psychotic disorders.

Premigration social adversity and autism spectrum disorder.

BACKGROUND: Several studies suggest significant relationships between migration and autism spectrum disorder (ASD) but there are discrepant results. Given that no studies to date have included a pathological control group, the specificity of the results in ASD can be questioned. AIMS: To compare the migration experience (premigration, migratory trip, postmigration) in ASD and non-ASD pathological control groups, and study the relationships between migration and autism severity. METHOD: Parents' and grandparents' migrant status was compared in 30 prepubertal boys with ASD and 30 prepubertal boys without ASD but with language disorders, using a questionnaire including Human Development Index (HDI)/Inequality-adjusted Human Development Index (IHDI) of native countries. Autism severity was assessed using the Child Autism Rating Scale, Autism Diagnostic Observation Schedule and Autism Diagnostic Interview-Revised scales. RESULTS: The parents' and grandparents' migrant status frequency did not differ between ASD and control groups and was not associated with autism severity. The HDI/IHDI values of native countries were significantly lower for parents and grandparents of children with ASD compared with the controls, especially for paternal grandparents. Furthermore, HDI/IDHI levels from the paternal line (father and especially paternal grandparents) were significantly negatively correlated with autism severity, particularly for social interaction impairments. CONCLUSIONS: In this study, parents' and/or grandparents' migrant status did not discriminate ASD and pathological control groups and did not contribute either to autism severity. However, the HDI/IHDI results suggest that social adversity-related stress experienced in native countries, especially by paternal grandparents, is potentially a traumatic experience that may play a role in ASD development. A 'premigration theory of autism' is then proposed.

Compressive Garments in Individuals with Autism and Severe Proprioceptive Dysfunction: A Retrospective Exploratory Case Series.

(1) Background: Compression garments (CGs) are an adjuvant treatment for generalized joint hypermobility (GJH), including the Ehlers-Danlos syndrome/hypermobility types. The effects of CGs are likely to be related to better proprioceptive control. We aimed to explore the use of CGs in individuals with autism and severe proprioceptive dysfunction (SPD), including individuals with GJH, to control posture and challenging behaviors. (2) Methods: We retrospectively described 14 patients with autism and SPD, including seven with comorbid GJH, who were hospitalized for major challenging behaviors with remaining behavioral symptomatology after the implementation of multidisciplinary approaches, including medication, treatment of organic comorbidities, and behavioral restructuring. Each patient received a CG to wear for at least 1 h (but most often longer) per day for six weeks. We assessed challenging behaviors in these participants with the Aberrant Behavior Checklist (ABC), sensory integration with the Dunn questionnaire, and postural sway and motor performance using a self-designed motricity path at baseline, two weeks, and six weeks. (3) Results: We observed a significant effect on most ABC rating scores at two weeks, which persisted at six weeks (total score, p = 0.004; irritability, p = 0.007; hyperactivity, p = 0.001; lethargy, p = 0.001). Postural control in dorsal and profile positions was significantly improved between before and after wearing the CGs (p = 0.006 and 0.007, respectively). Motor performance was also significantly improved. However, we did not observe a significant change in Dunn sensory scores. During the six-week duration, the treatment was generally well-tolerated. A comorbid GJH diagnosis was not associated with a better outcome. (4) Conclusions: CGs appear to be a promising adjuvant treatment for both behavioral and postural impairments in individuals with autism and SPD.

ICT and autism care: state of the art.

PURPOSE OF REVIEW: Over the past 10 years, the use of information and communication technologies (ICTs) has increased in regard to the treatment of individuals with autism spectrum disorders (ASDs). ICT support mechanisms (e.g. computers, laptops, robots) are particularly attractive and are adapted to children with ASD. In addition, ICT algorithms can offer new perspectives for clinicians, outside direct apps or gaming proposals. Here, we will focus on the use of serious games and robots because of their attractiveness and their value in working on social skills. RECENT FINDINGS: The latest knowledge regarding the use of ICT in the forms of serious games and robotics applied to individuals with ASD shows that the field of serious games has already achieved interesting and promising results, although the clinical validations are not always complete. In the field of robotics, there are still many limitations on the use of ICT (e.g. most interaction are similar to the wizard of Oz), and questions remain concerning their eventual effectiveness. SUMMARY: To describe the implications of the findings for clinical practice or research, we describe two large projects, namely, JEMImE and Michelangelo, as examples of current studies that are aimed at enhancing social skills in children with ASD by including novel algorithms with clinical insights in robots or serious games.

Interpersonal Synchronization, Motor Coordination, and Control Are Impaired During a Dynamic Imitation Task in Children With Autism Spectrum Disorder.

Background: Impairments in imitation abilities have been commonly described in children with autism spectrum disorder (ASD). How motricity in interpersonal coordination impacts imitation, during long lasting semi-ecological conditions, has not been carefully investigated. Methods: Eighty-five children and adolescents (39 controls with typical development, TD; 29 patients with ASD; 17 patients with developmental coordination disorder, DCD), aged 6 to 20 years, participated to a behavioral paradigm in which participants, standing and moving, interacted with a virtual tightrope walker standing and moving as well. During the protocol, we measured automatically and continuously bodily postures and movements from RGB sensor recording to assess participants' behavioral imitation. Results: We show that (1) interpersonal synchronization (as evidenced by the synchrony between the participant's and the tightrope walker's bars) and (2) motor coordination (as evidenced by the synchrony between the participant's bar and its own head axis) increased with age and were more impaired in patients with ASD. Also, motor control as evidenced by the movement angle standard deviations of participants' bar and head were significantly impaired in ASD compared to TD or DCD. Conclusion: Interpersonal synchronization and motor coordination during ecological interaction show both subtle impairment in children with ASD as compared to children with TD or DCD. These results questioned how motricity mature in terms of motor control and proprioception in children with ASD.

Behavioral Own-Body-Transformations in Children and Adolescents With Typical Development, Autism Spectrum Disorder, and Developmental Coordination Disorder.

Background: In motor imitation, taking a partner's perspective often involves a mental body transformation from an embodied, ego-centered viewpoint to a disembodied, hetero-centered viewpoint. Impairments of both own-body-transformation (OBT) and abnormalities in visual-spatial processing have been reported in patients with neurodevelopmental disorders including autism spectrum disorder (ASD). In the context of a visual-motor interactive task, studying OBT impairments while disentangling the contribution of visual-spatial impairments associated with motor coordination problems has not been investigated. Methods: 85 children and adolescents (39 controls with typical development, TD; 29 patients with ASD; 17 patients with developmental coordination disorder, DCD), aged 6-19 years, participated in a behavioral paradigm in which participants interacted with a virtual tightrope walker (TW) standing and moving with him. The protocol enables to distinguish ego-centered and hetero-centered perspectives. Results: We show that (1) OBT was possible but difficult for children with neurodevelopmental disorders, as well as for TD children, when the task required the participant to perform a mental rotation in order to adopt a hetero-centered perspective. (2) Using multivariate models, hetero-centered perspective score was significantly associated with age, TW orientation, latency, and diagnosis. ASD and TD groups' performances were close and significantly correlated with age. However, it was not the case for DCD, since this group was specifically handicapped by visual-spatial impairments. (3) ASD and DCD did not perform similarly: motor performance as shown by movement amplitude was better in DCD than ASD. ASD motor response was more ambiguous and hardly readable. Conclusion: Changing perspective in a spatial environment is possible for patients with ASD although delayed compared with TD children. In patients with DCD, their visual-spatial impairments negatively modulated their performances in the experiment.

Hormonal Risk Factors for Osteoporosis: Different Profile Among Antipsychotics.

Objectives: Osteoporosis is a major risk factor for fracture and treatment is mainly preventive. Patients with severe psychiatric condition and treated with antipsychotics are at risk for vitamin D deficiency and iatrogenic hyperprolactinemia, two serious risk factors of osteoporosis. We aim to determine whether all antipsychotics are similar regarding the risk of osteoporosis in young patients. Methods: From January 2009 to March 2015, we determined the vitamin D blood level (VDBL) among 484 inpatients and from January 2012 to March 2015, we determined the prolactin blood level (PBL) among 205 inpatients. We systematically recorded well-documented risk factors (e.g., age, gender, ethnic origin, body mass index, or season) and suspected risk factors (e.g., disease type or antipsychotic treatment). Results: Up to 89% of the inpatients had a VDBL under the recommended threshold. Up to 60% of the inpatients had hyperprolactinemia. The multivariate model found a significant effect on VDBL for seasonality (higher VDBL in summer), ethnicity (lower VDBL in Black individuals), and treatment exposure. The multivariate model found a significant effect on PBL for gender and treatment exposure. In both models, aripiprazole had a safer profile compared with other antipsychotics. Conclusion: Because adolescence is a period of bone construction and a critical window of opportunity for maximizing bone mass, we recommend vitamin D supplementation in young patients with severe mental condition. It could be interesting to reconsider to regularly monitor PBL among youth patients treated with antipsychotic, with the exception of aripiprazole.

Therapeutic body wraps (TBW) for treatment of severe injurious behaviour in children with autism spectrum disorder (ASD): A 3-month randomized controlled feasibility study.

INTRODUCTION: The use of therapeutic body wraps (TBW) has been reported in small series or case reports, but has become controversial. OBJECTIVES: This is a feasibility, multicentre, randomized, controlled, open-label trial with blinded outcome assessment (PROBE design). SETTING: Children with autism and severe-injurious behaviours (SIB) were enrolled from 13 specialized clinics. INTERVENTIONS: Dry-sheet TBW (DRY group) vs. wet-sheet TBW (WET group). PRIMARY OUTCOME MEASURES: 3-month change in the Aberrant Behaviour Checklist irritability score (ABC-irritability) within per-protocol (PP) sample. RESULTS: From January 2008 to January 2015, we recruited 48 children (age range: 5.9 to 9.9 years, 78.1% male). Seven patients (4 in the DRY group, 3 in the WET group) were dropped from the study early and were excluded from PP analysis. At endpoint, ABC-irritability significantly improved in both groups (means (standard deviation) = -11.15 (8.05) in the DRY group and -10.57 (9.29) in the WET group), as did the other ABC scores and the Children Autism Rating scale score. However, there was no significant difference between groups. All but 5 patients were rated as much or very much improved. A repeated-measures analysis confirmed the significant improvement in ABC-irritability scores according to time (p < .0001), with no significant difference between the two groups (group effect: p = .55; interaction time x group: p = .27). Pooling both groups together, the mean 3-month change from baseline in ABC-irritability score was -10.90 (effect size = 1.59, p < .0001). CONCLUSIONS: We found that feasibility was overall satisfactory with a slow recruitment rate and a rather good attrition rate. TBW was a safe complementary therapy in this population. There was no difference between wet and dry TBW at 3 months, and ABC-irritability significantly decreased with both wet and dry sheet TBW. To assess whether TBW may constitute an alternative to medication or behavioural intervention for treating SIB in ASD patients, a larger randomized comparative trial (e.g. TBW vs. antipsychotics) is warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT03164746.

1q21.1 microduplication: large verbal-nonverbal performance discrepancy and ddPCR assays of HYDIN/HYDIN2 copy number.

Microduplication of chromosome 1q21.1 is observed in ~0.03% of adults. It has a highly variable, incompletely penetrant phenotype that can include intellectual disability, global developmental delay, specific learning disabilities, autism, schizophrenia, heart anomalies and dysmorphic features. We evaluated a 10-year-old-male with a 1q21.1 duplication by CGH microarray. He presented with major attention deficits, phonological dysphasia, poor fine motor skills, dysmorphia and mild autistic features, but not the typical macrocephaly. Neuropsychiatric evaluation demonstrated a novel phenotype: an unusually large discrepancy between non-verbal capacities (borderline-impaired WISC-IV index scores of 70 for Working Memory and 68 for Processing Speed) vs. strong verbal skills - scores of 126 for Verbal Comprehension (superior) and 111 for Perceptual Reasoning (normal). HYDIN2 has been hypothesized to underlie macrocephaly and perhaps cognitive deficits in this syndrome, but assessment of HYDIN2 copy number by microarray is difficult because of extensive segmental duplications. We performed whole-genome sequencing which supported HYDIN2 duplication (chr1:146,370,001-148,590,000, 2.22 Mb, hg38). To evaluate copy number more rigorously we developed droplet digital PCR assays of HYDIN2 (targeting unique 1 kb and 6 kb insertions) and its paralog HYDIN (targeting a unique 154 bp segment outside the HYDIN2 overlap). In an independent cohort, ddPCR was concordant with previous microarray data. Duplication of HYDIN2 was confirmed in the patient by ddPCR. This case demonstrates that a large discrepancy of verbal and non-verbal abilities can occur in 1q21.1 duplication syndrome, but it remains unclear whether this has a specific genomic basis. These ddPCR assays may be useful for future research on HYDIN2 copy number.

Evaluation of short-term efficacy of extraspinal cementoplasty for bone metastasis: A monocenter study of 31 patients.

OBJECTIVE: To study the effect on pain of per-cutaneous cementoplasty for painful extraspinal bone metastasis. METHOD: 43 patients with extraspinal bone metastasis were included between April 2006 and October 2014 in this retrospective monocenter study. The primary endpoint was pain level measured on a 0-10 numeric rating scale at week 1 after cementoplasty as compared with pre-cementoplasty. Secondary endpoints were long-term pain level and impact on quality of life and disability. RESULTS: Mean pain score was 4.2 (SD ±3.6) before cementoplasty and 1.09 (SD ±2.4) at week 1 (p = 0.005) (n = 31 patients). At 22 months after cementoplasty, quality of life and disability improved (according to the patient global assessment) for 47.6% and 52.2% of patients (n = 21patients). We did not find a predictor of good response. Cement leakage was the most common adverse event. CONCLUSION: Percutaneous cementoplasty of extraspinal bone metastasis is a rapidly efficient treatment with few adverse events. Its efficacy persists over time, with a benefit for disability and quality of life. Although this technique is only palliative, it should be considered in this situation.