Efficacy and safety of very early mobilisation within 24 h of stroke onset (AVERT): a randomised controlled trial

Background Early mobilisation after stroke is thought to contribute to the eff ects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke.MethodsWe did this parallel-group, single-blind, randomised controlled trial at 56 acute stroke units in five countries. Patients (aged ≥18 years) with ischaemic or haemorrhagic stroke, first or recurrent, who met physiological criteriawere randomly assigned (1:1), via a web-based computer generated block randomisation procedure (block size of six), to receive usual stroke-unit care alone or very early mobilisation in addition to usual care. Treatment with recombinant tissue plasminogen activator was allowed. Randomisation was stratified by study site and stroke severity. Patients, outcome assessors, and investigators involved in trial and data management were masked to treatment allocation. The primary outcome was a favourable outcome 3 months after stroke, defined as a modified Rankin Scale score of 0–2. We did analysis on an intention-to-treat basis. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000185561.FindingsBetween July 18, 2006, and Oct 16, 2014, we randomly assigned 2104 patients to receive either very early mobilisation (n=1054) or usual care (n=1050); 2083 (99%) patients were included in the 3 month follow-up assessment. 965 (92%) patients were mobilised within 24 h in the very early mobilisation group compared with 623 (59%) patients in the usual care group. Fewer patients in the very early mobilisation group had a favourable outcome than those in the usual care group (n=480 [46%] vs n=525 [50%]; adjusted odds ratio [OR] 0·73, 95% CI 0·59–0·90; p=0·004). 88 (8%) patients died in the very early mobilisation group compared with 72 (7%) patients in the usual care group (OR 1·34, 95% CI 0·93–1·93, p=0·113). 201 (19%) patients in the very early mobilisation group and 208 (20%) of those in the usual care group had a non-fatal serious adverse event, with no reduction in immobility-related complications with very early mobilisation.InterpretationFirst mobilisation took place within 24 h for most patients in this trial. The higher dose, very early mobilisation protocol was associated with a reduction in the odds of a favourable outcome at 3 months. Early mobilisation after stroke is recommended in many clinical practice guidelines worldwide, and our findings should affect clinical practice by refi ning present guidelines; however, clinical recommendations should be informed by future analyses of dose–response associations.

Systematic review of physical activity and cognitive development in early childhood

OBJECTIVES: To comprehensively review all observational and experimental studies examining the relationship between physical activity and cognitive development during early childhood (birth to 5 years). DESIGN: Systematic review. METHODS: Electronic databases were searched in July, 2014. No study design, date, or language limits were imposed on the search. Included studies had to be published, peer reviewed articles that satisfied the a priori determined population (apparently healthy children aged birth to 5 years), intervention (duration, intensity, frequency, or patterns of physical activity), comparator (various durations, intensity, or patterns of physical activity), and outcome (cognitive development) study criteria. Study quality and risk of bias were assessed in December 2014. RESULTS: A total of seven studies, representing 414 participants from five different countries met the inclusion criteria, including two observational and five experimental studies. Six studies found increased or higher duration/frequency of physical activity had statistically significant (p<0.05) beneficial effects on at least one cognitive development outcome, including 67% of the outcomes assessed in the executive function domain and 60% in the language domain. No study found that increased or higher duration/frequency of physical activity had statistically significant detrimental effects on cognitive development. Six of the seven studies were rated weak quality with a high risk of bias. CONCLUSIONS: This review provides some preliminary evidence that physical activity may have beneficial effects on cognitive development during early childhood. Given the shortage of the information and the weak quality of available evidence, future research is needed to strengthen the evidence base in this area.

Early recognition of ipilimumab-related autoimmune hypophysitis in patients with metastatic melanoma: case studies and recommendations for management

Ipilimumab is a human anti-CTLA-4 monoclonal antibody recently approved for the treatment of advanced melanoma. Stimulation of T-cell activity unmasks antitumor activity, but can cause immune-related adverse events. Autoimmune hypophysitis is of particular importance because its presentation can be subtle but life threatening. We present two cases where early recognition of ipilimumab-related autoimmune hypophysitis led to timely intervention and low subsequent morbidity, without compromise of antitumor effects. We provide recommendations for detection and management of this potentially life-threatening complication of ipilimumab.

Systematic review of sedentary behavior and cognitive development in early childhood

OBJECTIVE: To comprehensively review observational and experimental studies examining the relationship between sedentary behavior and cognitive development during early childhood (birth to 5years). METHOD: Electronic databases were searched in July, 2014 and no limits were imposed on the search. Included studies had to be peer-reviewed, published, and meet the a priori determined population (apparently healthy children aged birth to 5years), intervention (duration, types, and patterns of sedentary behavior), comparator (various durations, types, or patterns of sedentary behavior), and outcome (cognitive development) study criteria. Data extraction occurred in October and November 2014 and study quality and risk of bias were assessed in December 2014. RESULTS: A total of 37 studies, representing 14,487 participants from nine different countries were included. Thirty-one studies used observational study designs and six studies used experimental study designs. Across study designs, increased or higher screen time (most commonly assessed as television viewing (TV)), reading, child-specific TV content, and adult-specific TV content had detrimental (negative) associations with cognitive development outcomes for 38%, 0%, 8%, and 25% of associations reported, respectively, and beneficial (positive) associations with cognitive development outcomes for 6%, 60%, 13%, and 3% of associations reported, respectively. Ten studies were moderate quality and 27 studies were weak quality. CONCLUSIONS: The type of sedentary behavior, such as TV versus reading, may have different impacts on cognitive development in early childhood. Future research with reliable and valid tools and adequate sample sizes that examine multiple cognitive domains (e.g., language, spatial cognition, executive function, memory) are needed. Registration no. CRD42014010004.

Nonparametric discovery and analysis of learning patterns and autism subgroups from therapeutic data

The spectrum nature and heterogeneity within autism spectrum disorders (ASD) pose as a challenge for treatment. Personalisation of syllabus for children with ASD can improve the efficacy of learning by adjusting the number of opportunities and deciding the course of syllabus. We research the data-motivated approach in an attempt to disentangle this heterogeneity for personalisation of syllabus. With the help of technology and a structured syllabus, collecting data while a child with ASD masters the skills is made possible. The performance data collected are, however, growing and contain missing elements based on the pace and the course each child takes while navigating through the syllabus. Bayesian nonparametric methods are known for automatically discovering the number of latent components and their parameters when the model involves higher complexity. We propose a nonparametric Bayesian matrix factorisation model that discovers learning patterns and the way participants associate with them. Our model is built upon the linear Poisson gamma model (LPGM) with an Indian buffet process prior and extended to incorporate data with missing elements. In this paper, for the first time we have presented learning patterns deduced automatically from data mining and machine learning methods using intervention data recorded for over 500 children with ASD. We compare the results with non-negative matrix factorisation and K-means, which being parametric, not only require us to specify the number of learning patterns in advance, but also do not have a principle approach to deal with missing data. The F1 score observed over varying degree of similarity measure (Jaccard Index) suggests that LPGM yields the best outcome. By observing these patterns with additional knowledge regarding the syllabus it may be possible to observe the progress and dynamically modify the syllabus for improved learning.

Emotions mediate the relationship between autistic traits and disordered eating: a new autistic-emotional model for eating pathology

The aim of the study was to assess the extent of overlap between autistic traits, body dissatisfaction and disordered eating and to explore the mediating effects of negative attitudes towards emotional expression and emotion dysregulation. The sample comprised 416 university students (82% females, 17-48 years [M=19.76, SD=3.85]), who completed an online questionnaire assessing eating attitudes and behaviours (including dieting, bulimia and oral control), body dissatisfaction, and autistic traits (including the Autism Quotient [AQ] and its related subscales as well as the Empathising Quotient). Attitudes towards emotional expression and emotion regulation were also assessed. Results revealed that eating pathology correlated highly with all AQ subscales, with the exception of the attention to detail subscale. However, there was no significant relationship between empathising and eating pathology. Path-analyses indicated that emotion dysregulation, but not negative attitudes towards emotional expression, was a significant mediator of the relationship between AQ, body dissatisfaction and eating pathology. Direct relationships were also obtained for the AQ-bulimia and the AQ-oral control paths. Prevention and early intervention programs for eating pathology would likely benefit from addressing abnormalities in emotion processes in individuals who score highly on measures of autistic traits.

Early childhood education and care educators supporting parent-child relationships: a systematic literature review

Building strong relationships between children and parents is vital for children’s social and emotional development. A majority of children attend early childhood education and care (ECEC) settings where they experience a range of relationships (educator–child, educator– parent, parent–child). Educators build relationships with children and parents, yet their influence on parent–child relationships is not well understood. Therefore, an evaluation of interventions/programs designed to promote parent–child relationships in ECEC settings (long day care, occasional care and preschool) and a range of settings (play groups, community groups and health centers) was conducted. The search revealed 21 peer-reviewed studies and seven interventions: two conducted in ECEC settings and five in a range of parent–child support settings. All studies reported intervention efficacy, yet none examined educators’ influence on parent–child relationships. Investigation into current educator practices is recommended to ensure educators are supported to promote and nurture parent– child relationships, consequently strengthening children’s social and emotional development.