Body Mass Index and Thoracic Expansion in Post-COVID Dyspnea: A Secondary Analysis.

Dyspnea secondary to lung impairment can persist following the acute phase of COVID-19. Thoracic expansion measurements have been used as a diagnostic tool to evaluate chest wall mobility, respiratory function, and the effects of respiratory muscle strength training. Changes in chest wall mobility may occur because of altered chest biomechanics in individuals with respiratory diseases and an elevated body mass index (BMI). The purpose of this secondary analysis was to evaluate whether BMI influences thoracic expansion or forced expiratory volume over 1 second (FEV1) in individuals with persistent dyspnea following COVID-19. This study assessed the relationship between BMI and thoracic expansion, pulmonary symptoms, and exercise capacity following a home-based pulmonary rehabilitation intervention. A secondary data analysis was conducted with a sample of 19 adults with persistent dyspnea following COVID-19 infection who participated in a 12-week, home-based pulmonary rehabilitation study. Participants received expiratory muscle strength training devices and were instructed to perform pulmonary rehabilitation exercises three times per week over the study period. Pulmonary function, pulmonary symptoms, exercise capacity, and BMI measurements were collected. For analysis, study participants were divided into obese (BMI > 30 kg/m2) or nonobese (BMI < 30 kg/m2) categories. Correlations using the change scores from baseline to 12 weeks between thoracic expansion, FEV1, pulmonary symptoms, and exercise capacity were assessed. In addition, the minimal detectable change (MDC) in thoracic expansion was explored. Thoracic expansion was significantly improved after 12 weeks of training (p = .012) in the nonobese group. There was a significant correlation between the change in walking distance and pulmonary symptoms (r = -.738, p < .001) and in thoracic expansion (r = .544, p = .020), and walking distance, when controlling for BMI, but no change in FEV1. Average MDC was 1.28 for inspiration and 0.91 for expiration. Measurements of thoracic expansion were significantly lower in post-COVID individuals with an increased BMI. Individuals with persistent dyspnea and a higher BMI may require additional measures to increase chest mobility or to detect pulmonary changes following COVID-19.

Development of a Novel Evidence-Based Practice-Specific Competency for Doctor of Physical Therapy Students in Clinical Education: A Modified Delphi Approach.

INTRODUCTION: Evidence-based practice (EBP) results in high-quality care and decreases unwarranted variation in practice. REVIEW OF THE LITERATURE: Few performance criteria related to EBP are included in physical therapy clinical education (CE) performance measures, despite EBP requirements in Doctor of Physical Therapy education. The purpose of this study was to develop EBP-specific competencies that may be used for Doctor of Physical Therapy students for use throughout CE. SUBJECTS: Thirteen subject matter experts (SME) participated in this study. METHODS: Subject matter experts were asked to rank each core EBP competency, from a previously described framework, using a 3-point Likert scale, which included "Not Essential," "Essential," and "Not Sure." A consensus of 70% or greater for the "Essential" rating advanced the competency to the final Delphi round, whereas a consensus of 70% or greater for the "Not Essential" rating was required for competency elimination. Subject matter experts voted to either "Accept" or "Modify" the competencies that had reached the inclusion consensus threshold. All competencies that reached consensus for inclusion after all 3 rounds were included in the final EBP Domain of Competence. RESULTS: Consensus was achieved in round one for 38% (n = 26) of items. In round 2, a consensus was achieved for 20% (n = 8) of items. Of the items remaining after rounds 1 and 2, 6 overarching competencies were identified, and all remaining items served as descriptions and specifications in the final EBP Domain of Competence. DISCUSSION AND CONCLUSIONS: The 6 competencies developed from this study constitute the EBP Domain of Competence and may be used throughout CE to assess students' EBP competency in clinical practice.

Validation of the Comprehensive Feeding Practices Questionnaire among parents of 5- to 7-year-old children in Sweden.

Introduction: Parents' behaviours towards food and mealtimes, also known as parental feeding practices, are important in the development of children's eating habits. The Comprehensive Feeding Practices Questionnaire (CFPQ) was designed to measure parental feeding practices. The aim of this study was to evaluate the validity of the CFPQ in Sweden and to assess how it performs across different groups of people. Methods: Data were from the baseline of a trial promoting children's healthy dietary and physical activity behaviours, the Healthy School Start Plus intervention, conducted in 17 schools in the Stockholm region in Sweden. The CFPQ was completed by 263 parents (59% mothers) of 173 children, aged 5 to 7 years. Exploratory factor analysis and the omega reliability test were performed to identify the underlying factors in the data. Invariance testing was used to investigate the equivalence of these factors across parental sex, parental education and children's weight status. Results: Five factors were identified: monitoring of children's food intake, pressure to eat, restriction of food, use of food for emotional regulation, and healthy eating guidance. All five factors were invariant across parental sex and education, though some questions were excluded to achieve invariance. The monitoring, pressure to eat and emotional regulation factors were invariant across children's weight status. Discussion: These results suggest that the CFPQ is valid for use in Sweden, amongst parents of children aged 5 to 7 years. The measurement invariance allows for comparisons of all five underlying factors across mothers and fathers and parental education levels, though across children's weight status for only three factors. Due to the importance of parental feeding practices throughout childhood, this questionnaire should also be validated in other age groups in Sweden.

The Experiences of Australian School Mental Health Professionals during COVID-19 Lockdowns.

Young people have emerged as one of the most impacted groups from the COVID-19 pandemic and related restrictions to daily activities, with disruptions to schooling, social interactions, and connections. Simultaneously, students' access to school mental health professionals were restricted or modified. The aim of this paper was to identify how school mental health professionals supported and addressed the mental health needs of young people during COVID-19 restrictions in Australia. School mental health professionals were surveyed during the 2020 lockdowns using a questionnaire designed by researchers in the United States of America. The innovations school mental health staff adopted to support students during lockdowns and remote learning were presented, including telehealth services, digital resources, and the online training and support they received/provided. The barriers and facilitators to providing counselling and assessment services during lockdowns were identified, including issues with providing psychometric assessments during remote learning, and ethical concerns when delivering remote counselling to students. Recommendations have been included, which address how school mental health professionals could be supported to assess and treat young people during future pandemics and school restrictions.

Genomics of perivascular space burden unravels early mechanisms of cerebral small vessel disease.

Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause of stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly in the white matter. These were associated with white matter PVS already in young adults (N = 1,748; 22.1 ± 2.3 yr) and were enriched in early-onset leukodystrophy genes and genes expressed in fetal brain endothelial cells, suggesting early-life mechanisms. In total, 53% of white matter PVS risk loci showed nominally significant associations (27% after multiple-testing correction) in a Japanese population-based cohort (N = 2,862; 68.3 ± 5.3 yr). Mendelian randomization supported causal associations of high blood pressure with basal ganglia and hippocampal PVS, and of basal ganglia PVS and hippocampal PVS with stroke, accounting for blood pressure. Our findings provide insight into the biology of PVS and cerebral small vessel disease, pointing to pathways involving extracellular matrix, membrane transport and developmental processes, and the potential for genetically informed prioritization of drug targets.

Perspectives of practicing school psychologists during COVID-19: A multi-country, mixed methods investigation.

COVID-19 presented a range of challenges to the delivery of school psychology services in countries around the world. The current study aimed to investigate the practices of school psychologists from the United States of America, Australia, Germany, Canada, and the United Kingdom, including changes to practice and exploration of the factors that supported the delivery of school psychology services during the pandemic. Quantitative and qualitative data were collected from 1,030 school psychologists and analyzed using a mixed methods, multiple case study design. Differing impacts of the pandemic on the working hours of school psychologists were reported across countries. Participants in all countries reported a shift to online working, with an increased focus on consultation and intervention and a reduction in psychoeducational assessments. School psychologists from all nations emphazised the importance of self-care strategies, social connections and physical activity and the role of support via supervision or professional networks. Access to appropriate technology and responsive workplace policies and procedures were also identified as important. Results have implications for the internationalization of the school psychology profession and can inform international school psychology planning in response to future crises.

Gene-mapping study of extremes of cerebral small vessel disease reveals TRIM47 as a strong candidate.

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 776 and 7079 extreme small vessel disease samples for the genome-wide association study and whole-exome association study, respectively. The genome-wide association study identified significant association of common variants in 11 loci with extreme small vessel disease, of which the chr12q24.11 locus was not previously reported to be associated with any MRI marker of cerebral small vessel disease. The whole-exome association study identified significant associations of extreme small vessel disease with common variants in the 5' UTR region of EFEMP1 (chr2p16.1) and one probably damaging common missense variant in TRIM47 (chr17q25.1). Mendelian randomization supports the causal association of extensive small vessel disease severity with increased risk of stroke and Alzheimer's disease. Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. We observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Overall, our comprehensive gene-mapping study and preliminary functional evaluation suggests a putative role of TRIM47 in the pathophysiology of cerebral small vessel disease, making it an important candidate for extensive in vivo explorations and future translational work.

Integrated Child and Family Hub models for detecting and responding to family adversity: protocol for a mixed-methods evaluation in two sites.

INTRODUCTION: Integrated community healthcare Hubs may offer a 'one stop shop' for service users with complex health and social needs, and more efficiently use service resources. Various policy imperatives exist to implement Hub models of care, however, there is a dearth of research specifically evaluating Hubs targeted at families experiencing adversity. To contribute to building this evidence, we propose to co-design, test and evaluate integrated Hub models of care in two Australian community health services in low socioeconomic areas that serve families experiencing adversity: Wyndham Vale in Victoria and Marrickville in New South Wales. METHODS AND ANALYSIS: This multisite convergent mixed-methods study will run over three phases to (1) develop the initial Hub programme theory through formative research; (2) test and, then, (3) refine the Hub theory using empirical data. Phase 1 involves co-design of each Hub with caregivers, community members and practitioners. Phase 2 uses caregiver and Hub practitioner surveys at baseline, and 6 and 12 months after Hub implementation, and in-depth interviews at 12 months. Two stakeholder groups will be recruited: caregivers (n=100-200 per site) and Hub practitioners (n=20-30 per site). The intervention is a co-located Hub providing health, social, legal and community services with no comparator. The primary outcomes are caregiver-reported: (i) identification of, (ii) interventions received and/or (iii) referrals received for adversity from Hub practitioners. The study also assesses child, caregiver, practitioner and system outcomes including mental health, parenting, quality of life, care experience and service linkages. Primary and secondary outcomes will be assessed by examining change in proportions/means from baseline to 6 months, from 6 to 12 months and from baseline to 12 months. Service linkages will be analysed using social network analysis. Costs of Hub implementation and a health economics analysis of unmet need will be conducted. Thematic analysis will be employed to analyse qualitative data. ETHICS AND DISSEMINATION: Royal Children's Hospital and Sydney Local Health District ethics committees have approved the study (HREC/62866/RCHM-2020). Participants and stakeholders will receive results through meetings, presentations and publications. TRIAL REGISTRATION NUMBER: ISRCTN55495932.

The practices of psychologists working in schools during COVID-19: A multi-country investigation.

This exploratory study aimed to identify the ways psychologists working in schools supported students' mental health during school closures related to the COVID-19 pandemic. An online survey was developed to determine (a) how psychologists working in schools across the United States, Canada, Germany, and Australia supported students' mental health during COVID-19, (b) how their services changed during COVID-19, and (c) potential differences between countries concerning difficulties supporting students' mental health during this time. The survey was based on previous research and was subsequently piloted. Using convenience and snowball sampling, 938 participants (U.S. n = 665; Canada n = 48; Germany n = 140; Australia n = 85) completed the online survey. Overall, school psychology services across these four countries pivoted from psychoeducational assessments to virtual counseling, consultation, and the development/posting of online support directly to children or parents to use with their children. There was some variation between countries; during the pandemic, significantly more psychologists in Germany and Australia provided telehealth/telecounseling than those in the United States and Canada, and psychologists in Germany provided significantly more hardcopy material to support children than psychologists in other countries. There is a need to ensure psychologists have the appropriate technological skills to support school communities during periods of school closure, including, but not limited to, virtual counseling and the administration of psychoeducational assessments. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

COVID-19 and Australian school psychology: Qualitative perspectives for enhancing future practice.

The challenges and changes driven by the Coronavirus Disease 2019 (COVID-19) pandemic in the education sector have been linked to high rates of anxiety, depression, and post-traumatic symptoms in school-aged populations. Despite this, it is also acknowledged that children and young people can be resilient and adaptable, with the right support in place. In schools, psychologists play an important role in supporting students' learning, behavior, wellbeing, and mental health. The aim of this study is to investigate the practices of Australian school psychologists during COVID-19 related school closures, focusing on their experiences and challenges and how they adapted their practices. Twelve Australian school psychologists were interviewed and, after member checks were undertaken, interview transcripts were analyzed using thematic analysis. Six interrelated themes were identified including: (a) heightened student psychological stress, (b) alternative delivery modes and associated challenges, (c) close collaboration with families, (d) participants personal challenges during COVID-19, (e) assessment during COVID-19, and (f) possible long-term practice changes post pandemic. The results of this study have implications for policies to support students in future pandemics or where physical school attendance is disrupted (e.g., natural disasters).

Hyperdense artery sign, symptomatic infarct swelling and effect of alteplase in acute ischaemic stroke.

BACKGROUND: Alteplase improves functional outcomes of patients with acute ischaemic stroke, but its effects on symptomatic infarct swelling, an adverse complication of stroke and the influence of CT hyperdense artery sign (HAS) are unclear. This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association. METHODS: We included stroke patients whose prerandomisation scan was non-contrast CT. Raters, masked to clinical information, assessed baseline (prerandomisation) and follow-up (24-48 hours postrandomisation) CT scans for HAS, defined as an intracranial artery appearing denser than contralateral arteries. Symptomatic infarct swelling was defined as clinically significant neurological deterioration ≤7 days after stroke with radiological evidence of midline shift, effacement of basal cisterns or uncal herniation. RESULTS: Among 2961 patients, HAS presence at baseline was associated with higher risk of symptomatic infarct swelling (OR 2.21; 95% CI 1.42 to 3.44). Alteplase increased the risk of swelling (OR 1.69; 95% CI 1.11 to 2.57), with no difference between patients with and those without baseline HAS (p=0.49). In patients with baseline HAS, alteplase reduced the proportion with HAS at follow-up (OR 0.67; 95% CI 0.50 to 0.91), where HAS disappearance was associated with reduced risk of swelling (OR 0.25, 95% CI 0.14 to 0.47). CONCLUSION: Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS, it was also associated with accelerated clearance of HAS, which in return reduced swelling, providing further mechanistic insights to underpin the benefits of alteplase.

Association of common genetic variants with brain microbleeds: A genome-wide association study.

OBJECTIVE: To identify common genetic variants associated with the presence of brain microbleeds (BMBs). METHODS: We performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ε2 and ε4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs. RESULTS: BMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21-1.45]; p = 2.5 × 10-10). APOE ε4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19-1.50]; p = 1.0 × 10-6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86-1.25]; p = 0.68). APOE ε2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB. CONCLUSIONS: Genetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ε4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.

Neurology-related protein biomarkers are associated with cognitive ability and brain volume in older age.

Identifying biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. Here, we investigated the associations between plasma levels of 90 neurology-related proteins (Olink® Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N = 798), Lothian Birth Cohort 1921 (LBC1921, N = 165), and the INTERVAL BioResource (N = 4451). In the LBC1936, 22 of the proteins were significantly associated with general fluid cognitive ability (ß between -0.11 and -0.17). MRI-assessed total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. In an age-matched subsample of INTERVAL, effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936. Plasma levels of a number of neurology-related proteins are associated with general fluid cognitive ability in later life, mediated by brain volume in some cases.

Computational quantification of brain perivascular space morphologies: Associations with vascular risk factors and white matter hyperintensities. A study in the Lothian Birth Cohort 1936.

BACKGROUND AND PURPOSE: Perivascular Spaces (PVS), also known as Virchow-Robin spaces, seen on structural brain MRI, are important fluid drainage conduits and are associated with small vessel disease (SVD). Computational quantification of visible PVS may enable efficient analyses in large datasets and increase sensitivity to detect associations with brain disorders. We assessed the associations of computationally-derived PVS parameters with vascular factors and white matter hyperintensities (WMH), a marker of SVD. PARTICIPANTS: Community dwelling individuals (n = 700) from the Lothian Birth Cohort 1936 who had multimodal brain MRI at age 72.6 years (SD = 0.7). METHODS: We assessed PVS computationally in the centrum semiovale and deep corona radiata on T2-weighted images. The computationally calculated measures were the total PVS volume and count per subject, and the mean individual PVS length, width and size, per subject. We assessed WMH by volume and visual Fazekas scores. We compared PVS visual rating to PVS computational metrics, and tested associations between each PVS measure and vascular risk factors (hypertension, diabetes, cholesterol), vascular history (cardiovascular disease and stroke), and WMH burden, using generalized linear models, which we compared using coefficients, confidence intervals and model fit. RESULTS: In 533 subjects, the computational PVS measures correlated positively with visual PVS ratings (PVS count r = 0.59; PVS volume r = 0.61; PVS mean length r = 0.55; PVS mean width r = 0.52; PVS mean size r = 0.47). PVS size and width were associated with hypertension (OR 1.22, 95% CI [1.03 to 1.46] and 1.20, 95% CI [1.01 to 1.43], respectively), and stroke (OR 1.34, 95% CI [1.08 to 1.65] and 1.36, 95% CI [1.08 to 1.71], respectively). We found no association between other PVS measures and diabetes, hypercholesterolemia or cardiovascular disease history. Computational PVS volume, length, width and size were more strongly associated with WMH (PVS mean size versus WMH Fazekas score ß = 0.66, 95% CI [0.59 to 0.74] and versus WMH volume ß = 0.43, 95% CI [0.38 to 0.48]) than computational PVS count (WMH Fazekas score ß = 0.21, 95% CI [0.11 to 0.3]; WMH volume ß = 0.14, 95% CI [0.09 to 0.19]) or visual score. Individual PVS size showed the strongest association with WMH. CONCLUSIONS: Computational measures reflecting individual PVS size, length and width were more strongly associated with WMH, stroke and hypertension than computational count or visual PVS score. Multidimensional computational PVS metrics may increase sensitivity to detect associations of PVS with risk exposures, brain lesions and neurological disease, provide greater anatomic detail and accelerate understanding of disorders of brain fluid and waste clearance.

Correction: Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reaction time variability and brain white matter integrity.

OBJECTIVE: Mean speed of responding is the most commonly used measure in the assessment of reaction time (RT). An alternative measure is intraindividual variability (IIV): the inconsistency of responding across multiple trials of a test. IIV has been suggested as an important indicator of central nervous system functioning, and as such, there has been increasing interest in the associations between IIV and brain imaging metrics. Results however, have been inconsistent. The present seeks to provide a comprehensive evaluation of the associations between a variety of measures of brain white matter integrity and individual differences in choice RT (CRT) IIV. METHOD: MRI brain scans of members of the Lothian Birth Cohort 1936 were assessed to obtain measures of the volume and severity of white matter hyperintensities, and the integrity of brain white matter tracts. CRT was assessed with a 4 CRT task on a separate occasion. Data were analyzed using multiple regression (N range = 358-670). RESULTS: Greater volume of hyperintensities and more severe hyperintensities in frontal regions were associated with higher CRT IIV. White matter tract integrity, as assessed by both fractional anisotropy and mean diffusivity, showed the smallest effect sizes in associations with CRT IIV. Associations with hyperintensities were attenuated and no longer significant after controlling for M CRT. CONCLUSIONS: Taken together, the results of the present study suggested that IIV was not incrementally predictive of white matter integrity over mean speed. This is in contrast to previous reports, and highlights the need for further study. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Withdrawal from escalated cocaine self-administration impairs reversal learning by disrupting the effects of negative feedback on reward exploitation: a behavioral and computational analysis.

Addiction is regarded as a disorder of inflexible choice with behavior dominated by immediate positive rewards over longer-term negative outcomes. However, the psychological mechanisms underlying the effects of self-administered drugs on behavioral flexibility are not well understood. To investigate whether drug exposure causes asymmetric effects on positive and negative outcomes we used a reversal learning procedure to assess how reward contingencies are utilized to guide behavior in rats previously exposed to intravenous cocaine self-administration (SA). Twenty-four rats were screened for anxiety in an open field prior to acquisition of cocaine SA over six daily sessions with subsequent long-access cocaine SA for 7 days. Control rats (n = 24) were trained to lever-press for food under a yoked schedule of reinforcement. Higher rates of cocaine SA were predicted by increased anxiety and preceded impaired reversal learning, expressed by a decrease in lose-shift as opposed to win-stay probability. A model-free reinforcement learning algorithm revealed that rats with high, but not low cocaine escalation failed to exploit previous reward learning and were more likely to repeat the same response as the previous trial. Eight-day withdrawal from high cocaine escalation was associated, respectively, with increased and decreased dopamine receptor D2 (DRD2) and serotonin receptor 2C (HTR2C) expression in the ventral striatum compared with controls. Dopamine receptor D1 (DRD1) expression was also significantly reduced in the orbitofrontal cortex of high cocaine-escalating rats. These findings indicate that withdrawal from escalated cocaine SA disrupts how negative feedback is used to guide goal-directed behavior for natural reinforcers and that trait anxiety may be a latent variable underlying this interaction.

Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

OBJECTIVE: To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke. METHODS: The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging. RESULTS: Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, p < 0.001; OR = 0.73, 95% CI 0.66-0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, p = 0.004). CONCLUSION: Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.

Longitudinal serum S100ß and brain aging in the Lothian Birth Cohort 1936.

Elevated serum and cerebrospinal fluid concentrations of S100ß, a protein predominantly found in glia, are associated with intracranial injury and neurodegeneration, although concentrations are also influenced by several other factors. The longitudinal association between serum S100ß concentrations and brain health in nonpathological aging is unknown. In a large group (baseline N = 593; longitudinal N = 414) of community-dwelling older adults at ages 73 and 76 years, we examined cross-sectional and parallel longitudinal changes between serum S100ß and brain MRI parameters: white matter hyperintensities, perivascular space visibility, white matter fractional anisotropy and mean diffusivity (MD), global atrophy, and gray matter volume. Using bivariate change score structural equation models, correcting for age, sex, diabetes, and hypertension, higher S100ß was cross-sectionally associated with poorer general fractional anisotropy (r = -0.150, p = 0.001), which was strongest in the anterior thalamic (r = -0.155, p < 0.001) and cingulum bundles (r = -0.111, p = 0.005), and survived false discovery rate correction. Longitudinally, there were no significant associations between changes in brain imaging parameters and S100ß after false discovery rate correction. These data provide some weak evidence that S100ß may be an informative biomarker of brain white matter aging.

The Application of Adaptive Behaviour Models: A Systematic Review.

Adaptive behaviour has been viewed broadly as an individual's ability to meet the standards of social responsibilities and independence; however, this definition has been a source of debate amongst researchers and clinicians. Based on the rich history and the importance of the construct of adaptive behaviour, the current study aimed to provide a comprehensive overview of the application of adaptive behaviour models to assessment tools, through a systematic review. A plethora of assessment measures for adaptive behaviour have been developed in order to adequately assess the construct; however, it appears that the only definition on which authors seem to agree is that adaptive behaviour is what adaptive behaviour scales measure. The importance of the construct for diagnosis, intervention and planning has been highlighted throughout the literature. It is recommended that researchers and clinicians critically review what measures of adaptive behaviour they are utilising and it is suggested that the definition and theory is revisited.