Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.

Cognitive Speed in Neurodegenerative Disease: Comparing Mean Rate and Inconsistency Within and Across the Alzheimer's and Lewy Body Spectra in the COMPASS-ND Study.

Background: Alzheimer's disease (AD) and Lewy body disease (LBD) are characterized by early and gradual worsening perturbations in speeded cognitive responses. Objective: Using simple and choice reaction time tasks, we compared two indicators of cognitive speed within and across the AD and LBD spectra: mean rate (average reaction time across trials) and inconsistency (within person variability). Methods: The AD spectrum cohorts included subjective cognitive impairment (SCI, n = 28), mild cognitive impairment (MCI, n = 121), and AD (n = 45) participants. The LBD spectrum included Parkinson's disease (PD, n = 32), mild cognitive impairment in PD (PD-MCI, n = 21), and LBD (n = 18) participants. A cognitively unimpaired (CU, n = 39) cohort served as common benchmark. We conducted multivariate analyses of variance and discrimination analyses. Results: Within the AD spectrum, the AD cohort was slower and more inconsistent than the CU, SCI, and MCI cohorts. The MCI cohort was slower than the CU cohort. Within the LBD spectrum, the LBD cohort was slower and more inconsistent than the CU, PD, and PD-MCI cohorts. The PD-MCI cohort was slower than the CU and PD cohorts. In cross-spectra (corresponding cohort) comparisons, the LBD cohort was slower and more inconsistent than the AD cohort. The PD-MCI cohort was slower than the MCI cohort. Discrimination analyses clarified the group difference patterns. Conclusions: For both speed tasks, mean rate and inconsistency demonstrated similar sensitivity to spectra-related comparisons. Both dementia cohorts were slower and more inconsistent than each of their respective non-dementia cohorts.

Barriers and co-designed strategies for the implementation of negative pressure wound therapy in acute pediatric burn care in Australia: A mixed method study.

PURPOSE: Pediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies. METHODS: A sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes. RESULTS: Sixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning. CONCLUSION: Multiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

Exploring early life social and executive function development in infants and risk for autism: a prospective cohort study protocol of NICU graduates and infants at risk for cerebral palsy.

BACKGROUND: Delays in early social and executive function are predictive of later developmental delays and eventual neurodevelopmental diagnoses. There is limited research examining such markers in the first year of life. High-risk infant groups commonly present with a range of neurodevelopmental challenges, including social and executive function delays, and show higher rates of autism diagnoses later in life. For example, it has been estimated that up to 30% of infants diagnosed with cerebral palsy (CP) will go on to be diagnosed with autism later in life. METHODS: This article presents a protocol of a prospective longitudinal study. The primary aim of this study is to identify early life markers of delay in social and executive function in high-risk infants at the earliest point in time, and to explore how these markers may relate to the increased risk for social and executive delay, and risk of autism, later in life. High-risk infants will include Neonatal Intensive Care Unit (NICU) graduates, who are most commonly admitted for premature birth and/or cardiovascular problems. In addition, we will include infants with, or at risk for, CP. This prospective study will recruit 100 high-risk infants at the age of 3-12 months old and will track social and executive function across the first 2 years of their life, when infants are 3-7, 8-12, 18 and 24 months old. A multi-modal approach will be adopted by tracking the early development of social and executive function using behavioural, neurobiological, and caregiver-reported everyday functioning markers. Data will be analysed to assess the relationship between the early markers, measured from as early as 3-7 months of age, and the social and executive function as well as the autism outcomes measured at 24 months. DISCUSSION: This study has the potential to promote the earliest detection and intervention opportunities for social and executive function difficulties as well as risk for autism in NICU graduates and/or infants with, or at risk for, CP. The findings of this study will also expand our understanding of the early emergence of autism across a wider range of at-risk groups.

The assessment and management of foot and toe oedema as part of holistic lower limb care.

Toe and foot swelling can manifest as lymphoedema or chronic oedema but can also be a complication of the treatment of these conditions. In this article, the authors discuss the assessment and treatment options for toe and foot swelling, highlighting the importance of prevention in the first instance.

Strategies used during the cognitive evaluation of older adults with dual sensory impairment: a scoping review.

BACKGROUND: Dual sensory impairment (DSI), the combination of visual and hearing impairments, is associated with increased risk for age-related cognitive decline and dementia. Administering cognitive tests to individuals with sensory impairment is challenging because most cognitive measures require sufficient hearing and vision. Considering sensory limitations during cognitive test administration is necessary so that the effects of sensory and cognitive abilities on test performance can be differentiated and the validity of test results optimized. OBJECTIVE: To review empirical strategies that researchers have employed to accommodate DSI during cognitive testing of older adults. METHODS: Seven databases (MEDLINE, Embase, Web of Science, CINAHL, PsycINFO, Global Health and the Evidence-Based Medicine Reviews databases) were searched for relevant articles integrating the three concepts of cognitive evaluation, aging, and DSI. Given the inclusion criteria, this scoping review included a total of 67 papers. RESULTS: Twenty-eight studies reported five categories of strategies for cognitive testing of older adult participants with DSI: the assistance of experts, the modification of standardized test scoring procedures, the use of communication strategies, environmental modifications, and the use of cognitive tests without visual and/or auditory items. CONCLUSIONS: The most used strategy reported in the included studies was drawing on the assistance of team members from related fields during the administration and interpretation of cognitive screening measures. Alternative strategies were rarely employed. Future research is needed to explore the knowledge-to-practice gap between research and current clinical practice, and to develop standardized testing strategies.

A network approach to subjective cognitive decline: Exploring multivariate relationships in neuropsychological test performance across Alzheimer's disease risk states.

Subjective cognitive decline (SCD) is characterized by subjective concerns of cognitive change despite test performance within normal range. Although those with SCD are at higher risk for developing further cognitive decline, we still lack methods using objective cognitive measures that reliably distinguish SCD from cognitively normal aging at the group level. Network analysis may help to address this by modeling cognitive performance as a web of intertwined cognitive abilities, providing insight into the multivariate associations determining cognitive status. Following previous network studies of mild cognitive impairment (MCI) and Alzheimer's dementia (AD), the current study centered upon the novel visualization and analysis of the SCD cognitive network compared to cognitively normal (CN) older adult, MCI, and AD group networks. Cross-sectional neuropsychological data from CIMA-Q and COMPASS-ND cohorts were used to construct Gaussian graphical models for CN (n = 122), SCD (n = 207), MCI (n = 210), and AD (n = 79) groups. Group networks were explored in terms of global network structure, prominent edge weights, and strength centrality indices. CN and SCD group networks were contrasted using the Network Comparison Test. Results indicate that CN and SCD groups did not differ in univariate cognitive performance or global network structure. However, measures of strength centrality, principally in executive functioning and processing speed, showed a CN-SCD-MCI gradient where subtle differences within the SCD network suggest that SCD is an intermediary between CN and MCI stages. Additional results may indicate a distinctiveness of network structure in AD, a reversal in network influence between age and general cognitive status as clinical impairment increases, and potential evidence for cognitive reserve. Together, these results provide evidence that network-specific metrics are sensitive to cognitive performance changes across the dementia risk spectrum and can help to objectively distinguish SCD group cognitive performance from that of the CN group.

Triage tools for detecting cervical spine injury in paediatric trauma patients.

BACKGROUND: Paediatric cervical spine injury (CSI) after blunt trauma is rare but can have severe consequences. Clinical decision rules (CDRs) have been developed to guide clinical decision-making, minimise unnecessary tests and associated risks, whilst detecting all significant CSIs. Several validated CDRs are used to guide imaging decision-making in adults following blunt trauma and clinical criteria have been proposed as possible paediatric-specific CDRs. Little information is known about their accuracy. OBJECTIVES: To assess and compare the diagnostic accuracy of CDRs or sets of clinical criteria, alone or in comparison with each other, for the evaluation of CSI following blunt trauma in children. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, and six other databases from 1 January 2015 to 13 December 2022. As we expanded the index test eligibility for this review update, we searched the excluded studies from the previous version of the review for eligibility. We contacted field experts to identify ongoing studies and studies potentially missed by the search. There were no language restrictions. SELECTION CRITERIA: We included cross-sectional or cohort designs (retrospective and prospective) and randomised controlled trials that compared the diagnostic accuracy of any CDR or clinical criteria compared with a reference standard for the evaluation of paediatric CSI following blunt trauma. We included studies evaluating one CDR or comparing two or more CDRs (directly and indirectly). We considered X-ray, computed tomography (CT) or magnetic resonance imaging (MRI) of the cervical spine, and clinical clearance/follow-up as adequate reference standards. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts for relevance, and carried out eligibility, data extraction and quality assessment. A third review author arbitrated. We extracted data on study design, participant characteristics, inclusion/exclusion criteria, index test, target condition, reference standard and data (diagnostic two-by-two tables) and calculated and plotted sensitivity and specificity on forest plots for visual examination of variation in test accuracy. We assessed methodological quality using the Quality Assessment of Diagnostic Accuracy Studies Version 2 tool. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included five studies with 21,379 enrolled participants, published between 2001 and 2021. Prevalence of CSI ranged from 0.5% to 1.85%. Seven CDRs were evaluated. Three studies reported on direct comparisons of CDRs. One study (973 participants) directly compared the accuracy of three index tests with the sensitivities of NEXUS, Canadian C-Spine Rule and the PECARN retrospective criteria being 1.00 (95% confidence interval (CI) 0.48 to 1.00), 1.00 (95% CI 0.48 to 1.00) and 1.00 (95% CI 0.48 to 1.00), respectively. The specificities were 0.56 (95% CI 0.53 to 0.59), 0.52 (95% CI 0.49 to 0.55) and 0.32 (95% CI 0.29 to 0.35), respectively (moderate-certainty evidence). One study (4091 participants) compared the accuracy of the PECARN retrospective criteria with the Leonard de novo model; the sensitivities were 0.91 (95% CI 0.81 to 0.96) and 0.92 (95% CI 0.83 to 0.97), respectively. The specificities were 0.46 (95% CI 0.44 to 0.47) and 0.50 (95% CI 0.49 to 0.52) (moderate- and low-certainty evidence, respectively). One study (270 participants) compared the accuracy of two NICE (National Institute for Health and Care Excellence) head injury guidelines; the sensitivity of the CG56 guideline was 1.00 (95% CI 0.48 to 1.00) compared to 1.00 (95% CI 0.48 to 1.00) with the CG176 guideline. The specificities were 0.46 (95% CI 0.40 to 0.52) and 0.07 (95% CI 0.04 to 0.11), respectively (very low-certainty evidence). Two additional studies were indirect comparison studies. One study (3065 participants) tested the accuracy of the NEXUS criteria; the sensitivity was 1.00 (95% CI 0.88 to 1.00) and specificity was 0.20 (95% CI 0.18 to 0.21) (low-certainty evidence). One retrospective study (12,537 participants) evaluated the PEDSPINE criteria and found a sensitivity of 0.93 (95% CI 0.78 to 0.99) and specificity of 0.70 (95% CI 0.69 to 0.72) (very low-certainty evidence). We did not pool data within the broader CDR categories or investigate heterogeneity due to the small quantity of data and the clinical heterogeneity of studies. Two studies were at high risk of bias. We identified two studies that are awaiting classification pending further information and two ongoing studies. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine the diagnostic test accuracy of CDRs to detect CSIs in children following blunt trauma, particularly for children under eight years of age. Although most studies had a high sensitivity, this was often achieved at the expense of low specificity and should be interpreted with caution due to a small number of CSIs and wide CIs. Well-designed, large studies are required to evaluate the accuracy of CDRs for the cervical spine clearance in children following blunt trauma, ideally in direct comparison with each other.

APOE-ε4 is not associated with pure-tone hearing thresholds, visual acuity or cognition, cross-sectionally or over 3 years of follow up in the Canadian Longitudinal Study on Aging.

INTRODUCTION: Hearing loss and diminished visual acuity are associated with poorer cognition, but the underlying mechanisms are not understood. The apolipoprotein (APOE) ε4 allelic variant may drive the associations. We tested whether APOE-ε4 allele count (0, 1, or 2) was associated with declines in memory, executive function, pure-tone hearing threshold averages, and pinhole-corrected visual acuity among participants in the Canadian Longitudinal Study on Aging (CLSA). METHODS: Multivariable linear mixed regression models were utilized to assess associations between APOE-ε4 allele count and each of the outcome variables. For each main effects model, interactions between APOE-ε4 and sex and age group (45-54-, 55-64-, 65-74-, and 75-85 years) respectively, were analyzed. RESULTS: Significant associations were not observed in main effects models. Models including APOE-ε4 * age (but not APOE-ε4 * sex) interaction terms better fit the data compared to main effects models. In age group-stratified models, however, there were minimal differences in effect estimates according to allele count. CONCLUSION: APOE-ε4 allele count does not appear to be a common cause of sensory-cognitive associations in this large cohort.

Host gene expression signatures to identify infection type and organ dysfunction in children evaluated for sepsis: a multicentre cohort study.

BACKGROUND: Sepsis is defined as dysregulated host response to infection that leads to life-threatening organ dysfunction. Biomarkers characterising the dysregulated host response in sepsis are lacking. We aimed to develop host gene expression signatures to predict organ dysfunction in children with bacterial or viral infection. METHODS: This cohort study was done in emergency departments and intensive care units of four hospitals in Queensland, Australia, and recruited children aged 1 month to 17 years who, upon admission, underwent a diagnostic test, including blood cultures, for suspected sepsis. Whole-blood RNA sequencing of blood was performed with Illumina NovaSeq (San Diego, CA, USA). Samples with completed phenotyping, monitoring, and RNA extraction by March 31, 2020, were included in the discovery cohort; samples collected or completed thereafter and by Oct 27, 2021, constituted the Rapid Paediatric Infection Diagnosis in Sepsis (RAPIDS) internal validation cohort. An external validation cohort was assembled from RNA sequencing gene expression count data from the observational European Childhood Life-threatening Infectious Disease Study (EUCLIDS), which recruited children with severe infection in nine European countries between 2012 and 2016. Feature selection approaches were applied to derive novel gene signatures for disease class (bacterial vs viral infection) and disease severity (presence vs absence of organ dysfunction 24 h post-sampling). The primary endpoint was the presence of organ dysfunction 24 h after blood sampling in the presence of confirmed bacterial versus viral infection. Gene signature performance is reported as area under the receiver operating characteristic curves (AUCs) and 95% CI. FINDINGS: Between Sept 25, 2017, and Oct 27, 2021, 907 patients were enrolled. Blood samples from 595 patients were included in the discovery cohort, and samples from 312 children were included in the RAPIDS validation cohort. We derived a ten-gene disease class signature that achieved an AUC of 94·1% (95% CI 90·6-97·7) in distinguishing bacterial from viral infections in the RAPIDS validation cohort. A ten-gene disease severity signature achieved an AUC of 82·2% (95% CI 76·3-88·1) in predicting organ dysfunction within 24 h of sampling in the RAPIDS validation cohort. Used in tandem, the disease class and disease severity signatures predicted organ dysfunction within 24 h of sampling with an AUC of 90·5% (95% CI 83·3-97·6) for patients with predicted bacterial infection and 94·7% (87·8-100·0) for patients with predicted viral infection. In the external EUCLIDS validation dataset (n=362), the disease class and disease severity predicted organ dysfunction at time of sampling with an AUC of 70·1% (95% CI 44·1-96·2) for patients with predicted bacterial infection and 69·6% (53·1-86·0) for patients with predicted viral infection. INTERPRETATION: In children evaluated for sepsis, novel host transcriptomic signatures specific for bacterial and viral infection can identify dysregulated host response leading to organ dysfunction. FUNDING: Australian Government Medical Research Future Fund Genomic Health Futures Mission, Children's Hospital Foundation Queensland, Brisbane Diamantina Health Partners, Emergency Medicine Foundation, Gold Coast Hospital Foundation, Far North Queensland Foundation, Townsville Hospital and Health Services SERTA Grant, and Australian Infectious Diseases Research Centre.

Audiovisual speech perception in noise in younger and older bilinguals.

Speech perception in noise becomes increasingly difficult with age. Similarly, bilinguals often have difficulty with speech perception in noise in their second language (L2) due to less developed language knowledge in L2. Little is known about older bilinguals, who experience age-related sensory and cognitive changes but have extensive L2 experience. Furthermore, while audiovisual (AV) speech cues and supportive sentence context facilitate speech perception in noise in native listeners, much less is known for bilingual listeners, particularly older bilinguals. This study investigated how much young (n = 30) and older (n = 31) French-English/English-French bilinguals benefit from AV speech cues and sentence context in their first (L1) and second language during speech perception in noise. Participants completed the task in L1 and L2. Importantly, the level of background noise was individually calibrated for each participant to equate performance during the baseline task. The results suggest that there were no age differences in overall performance during the speech perception in noise task. However, older adults showed smaller language effects and smaller modality effects (i.e., comparing auditory-only speech perception to audiovisual speech perception) compared to younger adults. Furthermore, both young and older bilinguals benefited from AV speech cues and sentence context in both of their languages. However, during L2 speech perception in noise, visual speech cues were particularly important for young adults. In contrast, older adults show equal benefit from visual speech cues in L1 and L2. Taken together, these findings extend current models of AV speech perception to a second language in both younger and older adults. Furthermore, the findings suggest that bilinguals are likely to benefit from visual speech cues and supportive sentence context, although this benefit may differ slightly between younger and older bilinguals. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Appraisal of Australian and New Zealand paediatric sepsis guidelines.

OBJECTIVE: Clinical practice guidelines (CPGs) are an important tool for the management of children with sepsis. The quality, consistency and concordance of Australian and New Zealand (ANZ) childhood sepsis CPGs with the Australian Commission on Safety and Quality in Healthcare (ACSQHC) sepsis clinical care standards and international sepsis guidelines is unclear. METHODS: We accessed childhood sepsis CPGs for all ANZ states and territories through Paediatric Research in Emergency Departments International Collaborative members. The guidelines were assessed for quality using the AGREE-II instrument. Consistency between CPG treatment recommendations was assessed, as was concordance with the ACSQHC sepsis clinical care standards and international sepsis guidelines. RESULTS: Overall, eight CPGs were identified and assessed. CPGs used a narrative and pathway format, with those using both having the highest quality overall. CPG quality was highest for description of scope and clarity of presentation, and lowest for editorial independence. Consistency between guidelines for initial treatment recommendations was poor, with substantial variation in the choice and urgency of empiric antimicrobial administration; the choice, volume and urgency of fluid resuscitation; and the choice of first-line vasoactive agent. Most CPGs were concordant with time-critical components of the ACSQHC sepsis clinical care standard, although few addressed post-acute care. Concordance with international sepsis guidelines was poor. CONCLUSION: Childhood sepsis CPGs in current use in ANZ are of variable quality and lack consistency with key treatment recommendations. CPGs are concordant with the ACSQHC care standard, but not with international sepsis guidelines. A bi-national sepsis CPG may reduce unnecessary variation in care.

Comparing easywrap with six other adjustable wraps for compression therapy in venous and lymphatic disease by variation in pressure, stiffness and elasticity.

BACKGROUND: There is no clear guidance or comprehensive comparative evidence to help clinicians select between adjustable wraps for compression therapy. However, adjustable wraps could be compared with three metrics used for compression bandages: variation in pressure, stiffness and elasticity. AIMS: To determine whether easywrap (Haddenham Healthcare) had lower standard deviation (SD) in lying pressure, greater static stiffness index (SSI) and/or a greater mean elongation ratio than six other adjustable wraps. METHODS: In this preliminary exploratory study, seven adjustable wraps were tested in vivo 20 times each (140 tests in total), on 20 people (with a variable number of readings per participant), to give the SD in lying pressure and mean SSI. The same wraps were tested in vitro five times each to give the mean elongation ratio. FINDINGS: Of all seven adjustable wraps, easywrap had the second lowest SD in lying pressure at 5.9 mmHg, compared with 8.9 mmHg overall; the highest mean SSI at 13.2 mmHg, compared with 9.5 mmHg overall; and the highest mean elongation ratio at 137.0%, compared with 107.1% overall. CONCLUSIONS: These metrics suggest that easywrap has clinical advantages over other adjustable wraps. A lower variation in lying pressure suggests more consistent application of pressures within intended therapeutic levels. Higher SSI indicates greater resistance to stretching, which is linked to improved venous function and oedema reduction. Higher elongation ratio demonstrates greater tensile strength, which should maintain therapeutic pressure for longer without readjustment.

Serum Levels of Vitamin C and Thiamin in Children With Suspected Sepsis: A Prospective Observational Cohort Study.

OBJECTIVES: Vitamin C and thiamin have been trialed as adjunctive therapies in adults with septic shock but their role in critically ill children is unclear. We assessed serum levels of vitamin C and thiamin in children evaluated for sepsis. DESIGN: Single-center prospective observational study. Serum levels of vitamin C and thiamin were measured on admission and association with multiple organ dysfunction syndrome (MODS) was explored using logistic regression. SETTING: Emergency department and PICU in a tertiary children's hospital, Queensland, Australia. PATIENTS: Children greater than 1 month and less than 17 years evaluated for sepsis. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Vitamin levels were determined in 221 children with a median age of 3.5 (interquartile range [IQR] 1.6, 8.3) years. Vitamin C levels were inversely correlated with severity as measured by pediatric Sequential Organ Failure Assessment (Spearman's rho = -0.16, p = 0.018). Median (IQR) vitamin C levels on admission were 35.7 (17.9, 54.1) µmol/L, 36.1 (21.4, 53.7) µmol/L, and 17.9 (6.6, 43.0) µmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.017). In multivariable analyses, low levels of vitamin C at the time of sampling were associated with greater odds of MODS (adjusted odds ratio [aOR] 3.04; 95% CI, 1.51-6.12), and vitamin C deficiency was associated with greater odds of MODS at 24 hours after sampling (aOR 3.38; 95% CI, 1.53-7.47). Median (IQR) thiamin levels were 162 (138, 192) nmol/L, 185 (143, 200) nmol/L, and 136 (110, 179) nmol/L in children without organ dysfunction, single organ dysfunction, and MODS, respectively (p = 0.061). We failed to identify an association between thiamin deficiency and either MODS at sampling (OR 2.52; 95% CI, 0.15-40.86) or MODS at 24 hours (OR 2.96; 95% CI, 0.18-48.18). CONCLUSIONS: Critically ill children evaluated for sepsis frequently manifest decreased levels of vitamin C, with lower levels associated with higher severity.

Resuscitation With Early Adrenaline Infusion for Children With Septic Shock: A Randomized Pilot Trial.

OBJECTIVES: In children with septic shock, guidelines recommend resuscitation with 40-60 mL/kg of fluid boluses, yet there is a lack of evidence to support this practice. We aimed to determine the feasibility of a randomized trial comparing early adrenaline infusion with standard fluid resuscitation in children with septic shock. DESIGN: Open-label parallel randomized controlled, multicenter pilot study. The primary end point was feasibility; the exploratory clinical endpoint was survival free of organ dysfunction by 28 days. SETTING: Four pediatric Emergency Departments in Queensland, Australia. PATIENTS: Children between 28 days and 18 years old with septic shock. INTERVENTIONS: Patients were assigned 1:1 to receive a continuous adrenaline infusion after 20 mL/kg fluid bolus resuscitation (n = 17), or standard care fluid resuscitation defined as delivery of 40 to 60 mL/kg fluid bolus resuscitation prior to inotrope commencement (n = 23). MEASUREMENTS AND MAIN RESULTS: Forty of 58 eligible patients (69%) were consented with a median age of 3.7 years (interquartile range [IQR], 0.9-12.1 yr). The median time from randomization to inotropes was 16 minutes (IQR, 12-26 min) in the intervention group, and 49 minutes (IQR, 29-63 min) in the standard care group. The median amount of fluid delivered during the first 24 hours was 0 mL/kg (IQR, 0-10.0 mL/kg) in the intervention group, and 20.0 mL/kg (14.6-28.6 mL/kg) in the standard group (difference, -20.0; 95% CI, -28.0 to -12.0). The number of days alive and free of organ dysfunction did not differ between the intervention and standard care groups, with a median of 27 days (IQR, 26-27 d) versus 26 days (IQR, 25-27 d). There were no adverse events reported associated with the intervention. CONCLUSIONS: In children with septic shock, a protocol comparing early administration of adrenaline versus standard care achieved separation between the study arms in relation to inotrope and fluid bolus use.

Sepsis epidemiology in Australian and New Zealand children (SENTINEL): protocol for a multicountry prospective observational study.

INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. METHODS AND ANALYSIS: This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures. ETHICS AND DISSEMINATION: Ethics approval was received from the Royal Children's Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000920897; Pre-results.

Does social connection mediate the association between neuroticism and cognition? Cross-sectional analysis of the Canadian Longitudinal Study on Aging.

OBJECTIVES: This study tested the association between neuroticism and six cognitive measures, and examined the potential mediating roles of social connection (social isolation and loneliness) among middle-aged and older adults. METHODS: This cross-sectional study was a secondary analysis of the Canadian Longitudinal Study on Aging (CLSA) Comprehensive Cohort, a sample of Canadians aged 45-85 years at baseline. Respondents with data collected at the first follow-up, between 2015 and 2018, were included (n = 27,765). Structural equation modelling was used to assess the association between neuroticism and six cognitive measures (Rey Auditory Verbal Learning Test immediate recall and delayed recall, Animal Fluency Test, Mental Alternation Test, Controlled Oral Word Association Test and Stroop Test interference ratio), with direct and indirect effects (through social isolation and loneliness). All analyses were stratified by sex, including females (n = 14,133) and males (n = 13,632). RESULTS: In unadjusted models, there was evidence of associations between neuroticism and all cognitive measures, except the Stroop Test interference ratio, suggesting higher neuroticism was associated with lower scores on memory and executive function tests. In the models of these other five outcomes, there was consistent evidence of indirect effects (through social isolation and loneliness) and, in some cases, direct effects. The results are discussed in context with limitations, including the use of cross-sectional design and alternative hypotheses to explain the association between personality and cognition. CONCLUSION: Among middle-aged and older adults, for both males and females, the findings suggest that the association between neuroticism and cognitive outcomes may be mediated by aspects of social connection.

Comparing easywrap with six other adjustable wraps for compression therapy in venous and lymphatic disease by variation in pressure, stiffness and elasticity.

BACKGROUND: There is no clear guidance or comprehensive comparative evidence to help clinicians select between adjustable wraps for compression therapy. However, adjustable wraps could be compared with three metrics used for compression bandages: variation in pressure, stiffness and elasticity. AIMS: To determine whether easywrap (Haddenham Healthcare) had lower standard deviation (SD) in lying pressure, greater static stiffness index (SSI) and/or a greater mean elongation ratio than six other adjustable wraps. METHODS: In this preliminary exploratory study, seven adjustable wraps were tested in vivo 20 times each (140 tests in total), on 20 people (with a variable number of readings per participant), to give the SD in lying pressure and mean SSI. The same wraps were tested in vitro five times each to give the mean elongation ratio. FINDINGS: Of all seven adjustable wraps, easywrap had the second lowest SD in lying pressure at 5.9 mmHg, compared with 8.9 mmHg overall; the highest mean SSI at 13.2 mmHg, compared with 9.5 mmHg overall; and the highest mean elongation ratio at 137.0%, compared with 107.1% overall. CONCLUSIONS: These metrics suggest that easywrap has clinical advantages over other adjustable wraps. A lower variation in lying pressure suggests more consistent application of pressures within intended therapeutic levels. Higher SSI indicates greater resistance to stretching, which is linked to improved venous function and oedema reduction. Higher elongation ratio demonstrates greater tensile strength, which should maintain therapeutic pressure for longer without readjustment.

Development and validation of risk of CPS decline (RCD): a new prediction tool for worsening cognitive performance among home care clients in Canada.

BACKGROUND: To develop and validate a prediction tool, or nomogram, for the risk of a decline in cognitive performance based on the interRAI Cognitive Performance Scale (CPS). METHODS: Retrospective, population-based, cohort study using Canadian Resident Assessment Instrument for Home Care (RAI-HC) data, collected between 2010 and 2018. Eligible home care clients, aged 18+, with at least two assessments were selected randomly for model derivation (75%) and validation (25%). All clients had a CPS score of zero (intact) or one (borderline intact) on intake into the home care program, out of a possible score of six. All individuals had to remain as home care recipients for the six months observation window in order to be included in the analysis. The primary outcome was any degree of worsening (i.e., increase) on the CPS score within six months. Using the derivation cohort, we developed a multivariable logistic regression model to predict the risk of a deterioration in the CPS score. Model performance was assessed on the validation cohort using discrimination and calibration plots. RESULTS: We identified 39,292 eligible home care clients, with a median age of 79.0 years, 62.3% were female, 38.8% were married and 38.6% lived alone. On average, 30.3% experienced a worsening on the CPS score within the six-month window (i.e., a change from 0 or 1 to 2, 3, 4, 5, or 6). The final model had good discrimination (c-statistic of 0.65), with excellent calibration. CONCLUSIONS: The model accurately predicted the risk of deterioration on the CPS score over six months among home care clients. This type of predictive model may provide useful information to support decisions for home care clinicians who use interRAI data internationally.

At-home computerized executive-function training to improve cognition and mobility in normal-hearing adults and older hearing aid users: a multi-centre, single-blinded randomized controlled trial.

BACKGROUND: Hearing loss predicts cognitive decline and falls risk. It has been argued that degraded hearing makes listening effortful, causing competition for higher-level cognitive resources needed for secondary cognitive or motor tasks. Therefore, executive function training has the potential to improve cognitive performance, in turn improving mobility, especially when older adults with hearing loss are engaged in effortful listening. Moreover, research using mobile neuroimaging and ecologically valid measures of cognition and mobility in this population is limited. The objective of this research is to examine the effect of at-home cognitive training on dual-task performance using laboratory and simulated real-world conditions in normal-hearing adults and older hearing aid users. We hypothesize that executive function training will lead to greater improvements in cognitive-motor dual-task performance compared to a wait-list control group. We also hypothesize that executive function training will lead to the largest dual-task improvements in older hearing aid users, followed by normal-hearing older adults, and then middle-aged adults. METHODS: A multi-site (Concordia University and KITE-Toronto Rehabilitation Institute, University Health Network) single-blinded randomized controlled trial will be conducted whereby participants are randomized to either 12 weeks of at-home computerized executive function training or a wait-list control. Participants will consist of normal-hearing middle-aged adults (45-60 years old) and older adults (65-80 years old), as well as older hearing aid users (65-80 years old, ≥ 6 months hearing aid experience). Separate samples will undergo the same training protocol and the same pre- and post-evaluations of cognition, hearing, and mobility across sites. The primary dual-task outcome measures will involve either static balance (KITE site) or treadmill walking (Concordia site) with a secondary auditory-cognitive task. Dual-task performance will be assessed in an immersive virtual reality environment in KITE's StreetLab and brain activity will be measured using functional near infrared spectroscopy at Concordia's PERFORM Centre. DISCUSSION: This research will establish the efficacy of an at-home cognitive training program on complex auditory and motor functioning under laboratory and simulated real-world conditions. This will contribute to rehabilitation strategies in order to mitigate or prevent physical and cognitive decline in older adults with hearing loss. TRIAL REGISTRATION: Identifier: NCT05418998. https://clinicaltrials.gov/ct2/show/NCT05418998.