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The objective was to explore the care experiences and service design related to rehabilitation for mobility and participation in the community among individuals with acquired brain injury (ABI), as perceived by clinicians and patients. Five focus groups were held: three with clinicians and two with individuals with ABI. Focus group discussions were transcribed and analyzed using an inductive and deductive thematic content approach. Five themes were identified: Enabling continuity of care; System design; Accessibility and services in the community; Transportation services; and Uncertainty about the provided services. The results of participants' experiences contributed to developing recommendations of service provision for mobility, leading to a patient-centered continuum of rehabilitation services. Accessibility to rehabilitation to improve the quality of care by addressing needs during transitions and mobility-related deficits, providing needed information, coordinated care, and self-management support in the community., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Alhasani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Summary: Background: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer’s disease (AD). Methods: Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age range spanning 42–85 years. Participants were categorised into four groups based on the difference between their chronological and predicted age in each modality: advanced age in both (n = 291), resilient in both (n = 260) or advanced in one/resilient in the other (n = 163/153). With the resilient group as the reference, brain-age groups were compared across neuroimaging features of neuropathology (white matter hyperintensity volume, neuronal loss measured with Neurite Orientation Dispersion and Density Imaging, AD-specific atrophy patterns measured with the Spatial Patterns of Abnormality for Recognition of Early Alzheimer’s Disease index, amyloid burden using amyloid positron emission tomography (PET), progression to mild cognitive impairment and baseline and longitudinal cognitive measures (trail making task, mini mental state examination, digit symbol substitution task). Findings: Individuals with advanced structural and functional brain-ages had more features indicative of neurodegeneration and they had poor cognition. Individuals with a resilient brain-age in both modalities had a genetic variant that has been shown to be associated with age of onset of AD. Mixed brain-age was associated with selective cognitive deficits. Interpretation: The advanced group displayed evidence of increased atrophy across all neuroimaging features that was not found in either of the mixed groups. This is in line with biomarkers of preclinical AD and cerebrovascular disease. These findings suggest that the variation in structural and functional brain ageing across individuals reflects the degree of underlying neuropathological processes and may indicate the propensity to develop dementia in later life. Funding: The National Institute on Aging, the National Institutes of Health, the Swiss National Science Foundation, the Kaiser Foundation Research Institute and the National Heart, Lung, and Blood Institute.

IntroductionDeregulation of the cerebrovascular system has been linked to neurodegeneration, part of a putative causal pathway into etiologies such as Alzheimer's disease (AD). In medical imaging, time-of-flight magnetic resonance angiography (TOF-MRA) and perfusion MRI are the most common modalities used to study this system. However, due to lack of resources, many large-scale studies of AD are not acquiring these images; this creates a conundrum, as the lack of evidence limits our knowledge of the interaction between the cerebrovascular system and AD. Deep learning approaches have been used in recent developments to generate synthetic medical images from existing contrasts. In this review, we study the use of artificial intelligence in the generation of synthetic TOF-MRA and perfusion-related images from existing neuroanatomical and neurovascular acquisitions for the study of the cerebrovascular system.MethodFollowing the PRISMA reporting guidelines we conducted a scoping review of 729 studies relating to image synthesis of TOF-MRA or perfusion imaging, from which 13 met our criteria.ResultsStudies showed that T1-w, T2-w, and FLAIR can be used to synthesize perfusion map and TOF-MRA. Other studies demonstrated that synthetic images could have a greater signal-to-noise ratio compared to real images and that some models trained on healthy subjects could generalize their outputs to an unseen population, such as stroke patients.DiscussionThese findings suggest that generating TOF-MRA and perfusion MRI images holds significant potential for enhancing neurovascular studies, particularly in cases where direct acquisition is not feasible. This approach could provide valuable insights for retrospective studies of several cerebrovascular related diseases such as stroke and AD. While promising, further research is needed to assess their sensitivity and specificity, and ensure their applicability across diverse populations. The use of models to generate TOF-MRA and perfusion MRI using commonly acquired data could be the key for the retrospective study of the cerebrovascular system and elucidate its role in the development of dementia.

BackgroundSurvivors of critical illness are at risk of developing physical dysfunction following intensive care unit (ICU) discharge. ICU-based rehabilitation interventions, such as early in-bed cycle ergometry, may improve patients’ short-term physical function. ObjectiveBefore unblinding and trial database lock, we describe a prespecified statistical analysis plan (SAP) for the CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) randomized controlled trial (RCT). MethodsCYCLE is a 360-patient, international, multicenter, open-label, parallel-group RCT (1:1 ratio) with blinded primary outcome assessment at 3 days post-ICU discharge. The principal investigator and statisticians of CYCLE prepared this SAP with approval from the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes (including adverse events) and describes the planned primary, secondary, and subgroup analyses. The primary outcome of the CYCLE trial is the Physical Function Intensive Care Unit Test-scored (PFIT-s) at 3 days post-ICU discharge. The PFIT-s is a reliable and valid performance-based measure. We plan to use a frequentist statistical framework for all analyses. We will conduct a linear regression to evaluate the primary outcome, incorporating randomization as an independent variable and adjusting for age (≥65 years versus

Abstract This study evaluated gait variability in patients before and after total knee arthroplasty (TKA) using the equality of variance method to determine where variability differences occur in the movement cycle. Twenty-eight patients underwent TKA with cruciate-sacrificed implants. Patients underwent motion analysis which measured knee biomechanics as they walked overground at their preferred pace before and 12 months after TKA. Equality of variance results were compared with 14 healthy controls of similar age. Before surgery, patients had reduced knee extension moment variability throughout the early stance phase (4–21% gait cycle, p

Abstract Knee osteoarthritis (OA) is a public health problem affecting millions of people worldwide. The intensity of the tibiofemoral contact forces is related to cartilage degeneration, and so is the importance of quantifying joint loads during daily activities. Although simulation with musculoskeletal models has been used to calculate joint loads, it demands high-cost equipment and a very time-consuming process. This study aimed to evaluate consolidated machine learning algorithms to predict tibiofemoral forces during gait analysis of healthy individuals and knee OA patients. Also, we evaluated three different datasets to train each model, considering different combinations of primary kinematic and kinetic data, and post-processing data. We evaluated 14 patients with severe unilateral knee OA and 14 healthy individuals during 3–5 gait trials. Data were split into 70% and 30% of the samples as training and test data. Test data was independently evaluated considering a mixture of pathological and healthy individuals, and only OA and Control patients. The main results showed that accurate predictions of the tibiofemoral contact forces were achieved using machine learning methods and that the predictions were sensitive to changes in the input data as training. The present study provided insights into the most promising regressions methods to predict knee contact forces representing an important starting point for the broader application of biomechanical analysis in clinical environments.

Abstract Randomized controlled trials (RCTs) have traditionally been considered the gold standard for medical evidence. However, in light of emerging methodologies in data science, many experts question the role of RCTs. Within this context, experts in the USA and Canada came together to debate whether the primacy of RCTs as the gold standard for medical evidence, still holds in light of recent methodological advances in data science and in the era of big data. The purpose of this manuscript, aims to raise awareness of the pros and cons of RCTs and observational studies in order to help guide clinicians, researchers, students, and decision-makers in making informed decisions on the quality of medical evidence to support their work. In particular, new and underappreciated advantages and disadvantages of both designs are contrasted. Innovations taking place in both of these research methodologies, which can blur the lines between the two, are also discussed. Finally, practical guidance for clinicians and future directions in assessing the quality of evidence is offered.

Abstract Identifying early signs of neurodegeneration due to Alzheimer’s disease (AD) is a necessary first step towards preventing cognitive decline. Individual cortical thickness measures, available after processing anatomical magnetic resonance imaging (MRI), are sensitive markers of neurodegeneration. However, normal aging cortical decline and high inter-individual variability complicate the comparison and statistical determination of the impact of AD-related neurodegeneration on trajectories. In this paper, we computed trajectories in a 2D representation of a 62-dimensional manifold of individual cortical thickness measures. To compute this representation, we used a novel, nonlinear dimension reduction algorithm called Uniform Manifold Approximation and Projection (UMAP). We trained two embeddings, one on cortical thickness measurements of 6237 cognitively healthy participants aged 18–100 years old and the other on 233 mild cognitively impaired (MCI) and AD participants from the longitudinal database, the Alzheimer’s Disease Neuroimaging Initiative database (ADNI). Each participant had multiple visits ( $$n \ge 2$$ n ≥ 2 ), one year apart. The first embedding’s principal axis was shown to be positively associated ( $$r = 0.65$$ r = 0.65 ) with participants’ age. Data from ADNI is projected into these 2D spaces. After clustering the data, average trajectories between clusters were shown to be significantly different between MCI and AD subjects. Moreover, some clusters and trajectories between clusters were more prone to host AD subjects. This study was able to differentiate AD and MCI subjects based on their trajectory in a 2D space with an AUC of 0.80 with 10-fold cross-validation.

Objective To describe stakeholder characteristics and perspectives about experiences, challenges and information needs related to the use of environmental scans (ESs).Design Cross-sectional study.Setting and participants A web-based survey platform was used to disseminate an online survey to stakeholders who had experience with conducting ESs in a health services delivery context (eg, researchers, policy makers, practitioners). Participants were recruited through purposive and snowball sampling. The survey was disseminated internationally, was available in English and French, and remained open for 6 weeks (15 October to 30 November 2022).Analysis Descriptive statistics were used to describe the characteristics and experiences of stakeholders. Thematic analysis was used to analyse the open-text questions.Results Of 47 participants who responded to the survey, 94% were from Canada, 4% from the USA and 2% from Australia. Respondents represented academic institutions (57%), health agency/government (32%) and non-government organisations or agencies (11%). Three themes were identified: (a) having a sense of value and utility; (b) experiencing uncertainty and confusion; and (c) seeking guidance. The data suggest stakeholders found value and utility in ESs and conducted them for varied purposes including to: (a) enhance knowledge, understanding and learning about the current landscape or state of various features of health services delivery (eg, programmes, practices, policies, services, best practices); (b) expose needs, service barriers, challenges, gaps, threats, opportunities; (c) help guide action for planning, policy and programme development; and (d) inform recommendations and decision-making. Stakeholders also experienced conceptual, methodological and practical barriers when conducting ESs, and expressed a need for methodological guidance delivered through published guidelines, checklists and other means.Conclusion ESs have value and utility for addressing health services delivery concerns, but conceptual and methodological challenges exist. Further research is needed to help advance the ES as a distinct design that provides a systematic approach to planning and conducting ESs.

Abstract Background Mild traumatic brain injury (mTBI) is an increasing public health problem, because of its persistent symptoms and several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help to guide the prevention of persistent symptoms following mTBI. The prognosis of mTBI has stimulated several empirical primary research papers and many systematic reviews leading to the identification of a wide range of factors. We aim to synthesize these factors to get a better understanding of their breadth and scope. Methods We conducted an overview of systematic reviews. We searched in databases systematic reviews synthesizing evidence about the prognosis of persistent symptoms after mTBI in the adult population. Two reviewers independently screened all references and selected eligible reviews based on eligibility criteria. They extracted relevant information using an extraction grid. They also rated independently the risk of bias using the ROBIS tool. We synthesized evidence into a comprehensive conceptual map to facilitate the understanding of prognostic factors that have an impact on persistent post-concussion symptoms. Results From the 3857 references retrieved in a database search, we included 25 systematic reviews integrating the results of 312 primary articles published between 1957 and 2019. We examined 35 prognostic factors from the systematics reviews. No single prognostic factor demonstrated convincing and conclusive results. However, age, sex, and multiple concussions showed an affirmatory association with persistent post-concussion outcomes in systematic reviews. Conclusion We highlighted the need for a comprehensive picture of prognostic factors related to persistent post-concussion symptoms. We believe that these prognostic factors would guide clinical decisions and research related to prevention and intervention regarding persistent post-concussion symptoms. Systematic review registration PROSPERO CRD42020176676

Brain processes associated with emotion perception from biological motion have been largely investigated using point-light displays that are devoid of pictorial information and not representative of everyday life. In this study, we investigated the brain signals evoked when perceiving emotions arising from body movements of virtual pedestrians walking in a community environment. Magnetoencephalography was used to record brain activation in 21 healthy young adults discriminating the emotional gaits (neutral, angry, happy) of virtual male/female pedestrians. Event-related responses in the posterior superior temporal sulcus (pSTS), fusiform body area (FBA), extrastriate body area (EBA), amygdala (AMG), and lateral occipital cortex (Occ) were examined. Brain signals were characterized by an early positive peak (P1;∼200ms) and a late positive potential component (LPP) comprising of an early (400-600ms), middle (600-1000ms) and late phase (1000-1500ms). Generalized estimating equations revealed that P1 amplitude was unaffected by emotion and gender of pedestrians. LPP amplitude showed a significant emotion X phase interaction in all regions of interest, revealing i) an emotion-dependent modulation starting in pSTS and Occ, followed by AMG, FBA and EBA, and ii) generally enhanced responses for angry vs. other gait stimuli in the middle LPP phase. LPP also showed a gender X phase interaction in pSTS and Occ, as gender affected the time course of the response to emotional gait. Present findings show that brain activation within areas associated with biological motion, form, and emotion processing is modulated by emotional gait stimuli rendered by virtual simulations representative of everyday life.

ObjectiveThe aim of the study was to explore perceptions of mental ill health, suicidal behaviour and working conditions among male construction workers, in order to gain an in-depth understanding of these phenomenon and to identify relevant avenues for workplace interventions.MethodData were collected in individual and group interviews, and 43 individuals from the Swedish construction industry, workers, union representative and managers, participated in the study. Inductive thematic analysis was used to analyse the data.ResultsFive main themes were found: Difficult to talk about mental health, Demanding working environment affects mental health, Substance abuse among construction workers, Importance of management, and Need for routines and social support in the workplace. Many participants reported that there was a stigma related to mental health. Suicides that had occurred among colleagues were perceived to come out of the blue. The working environment in the construction industry was perceived to have a negative effect on mental health, and it was reported that the management played an important role in both the cause and prevention of mental health problems.ConclusionsThe results from this Swedish study are in accordance with previous international research regarding a macho culture, stigma of mental health and a demanding working environment in the construction industry. The study adds to existing knowledge by highlighting that suicides were perceived to be very unexpected, that poor physical health affected mental health and that many participants did not know how to deal with mental health issues in the workplace.

Objectives This study assessed the associations of Internalised Homonegativity (IH) with HIV testing and risk behaviours of adult men who have sex with men (MSM) in sub-Saharan Africa (SSA) and effect modification by the legal climate.Design We used data from the cross-sectional 2019 Global Lesbian, Gay, Bisexual, Transgender and Intersex (LGBTI+) Internet survey study.Setting and participants Overall, the 2019 Global LGBTI Internet Survey collected data from 46 SSA countries. In this secondary analysis, we included data from 3191 MSM in 44 SSA countries as there were no eligible MSM responses in the 2 countries excluded.Outcome measures Our response variables were self-reported binary indicators of ever tested for HIV, recently tested in the past 6 months (from those who reported ever testing), transactional sex (paying for and being paid for sex in the past 12 months), and unprotected anal sex (that is without a condom or pre-exposure prohylaxis (PrEP)) with a non-steady partner (in the past 3 months).Results Our findings showed high levels of IH (range 1–7) in MSM across SSA (mean (SD)=5.3 (1.36)). We found that MSM with higher IH levels were more likely to have ever (adjusted OR (aOR) 1.18, 95% CI 1.03 to 1.35) and recently tested (aOR 1.19, 95% CI 1.07 to 1.32) but no evidence of an association with paying for sex (aOR 1.00, 95% CI 0.89 to 1.12), selling sex (aOR 1.06, 95% CI 0.95 to 1.20) and unprotected sex (aOR 0.99, 95% CI 0.89 to 1.09). However, we observed that a favourable legal climate modifies the associations of IH and paying for sex (aOR 0.75, 95% CI 0.60 to 0.94). Increasing levels of IH had a negative association with paying for sex in countries where same-sex relationships are legal. We found no associations of IH with unprotected anal sex in the population surveyed.Conclusions We confirm that IH is widespread across SSA but in countries that legalise same-sex relationships, MSM were less likely to engage in transactional sex compared with those in countries where homosexuality is criminalised.

Abstract In many Western countries, including Australia, construction workers have been identified as being at elevated risk of suicide compared to other workers. A variety of suicide prevention initiatives have been implemented and expanded to reduce suicide in this occupational group; however, the net effect of these is unknown. Using 19 years of national suicide data, this study examined the suicide mortality of Australian male construction workers relative to all other working males, and compared suicide rates over time between the two groups. Age-standardized suicide rates were calculated for construction workers and those employed in other occupations. 2001–2019 trends in age-standardized rates of suicide mortality were analyzed by joinpoint regression analysis. The annual average percentage change (AAPC) measure was calculated for both groups to quantify change over time within each group, complemented by a pair-wise AAPC comparison of changes in trends between the two groups over the 2001–2019 period. Australian male construction workers' overall age-standardized suicide rate was 26.6 per 100,000 persons compared to 13.2 per 100,000 for male workers employed in other occupations (pooled over the entire 2001–2019 period). Over time, the suicide mortality rate declined in both construction workers and those working in other occupations; however, the decline in suicide mortality was greater in construction workers (AAPC: −3.0; 95%CI −4.0, −2.0) compared to other workers (AAPC: 1.5; 95%CI −2.1, −1.0). The AAPC pair-wise comparison showed a significant difference between the rate of decline among construction versus other workers over the 19-year study period (AAPC: −1.4; 95%CI 0.4, 2.5), confirming a rapid decline among construction versus other male workers. This study provides evidence of a decline in suicide rates among Australian construction workers over the last two decades. This decline may be attributable to the combined effects of population-wide, male-specific, and sector-specific suicide prevention efforts over this same period, suggesting that the continuation or expansion of such efforts may lead to further declines.

Introduction In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults.Methods and analysis We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups.Ethics and dissemination Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations.Trial registration number NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

As of November 2023, 140 World Health Organization (WHO) member states had introduced human papillomavirus (HPV) vaccination in their routine immunization schedules. Despite a continuously increasing demand from countries across all income groups, supply constraints, COVID-19 pandemic disruptions, and other factors have slowed the pace of introduction, particularly in low-resource settings. Using a population-based forecasting methodology and leveraging the WHO’s yearly vaccine supply data collection, we updated global demand and supply projections for the HPV vaccine for the period of 2022–2031. The analysis aimed at clarifying the magnitude of the challenges to bringing in equitable access to HPV vaccines, which can hinder the achievement of the Global Strategy for the Elimination of Cervical Cancer. The results of this analysis show that the risk of HPV shortages has significantly decreased, and global supply is now, under normal circumstances, sufficient to meet global demand. In the long term, HPV supply will be more than sufficient to meet the Global Strategy’s goal of 90% of girls fully vaccinated with the HPV vaccine by the age of 15 years. Nonetheless, paying attention to the formulation of policies and carefully managing demand and supply will be required to ensure the long-term sustainability of the HPV vaccine program.

The objective was to explore the care experiences and service design related to rehabilitation for mobility and participation in the community among individuals with acquired brain injury (ABI), as perceived by clinicians and patients. Five focus groups were held: three with clinicians and two with individuals with ABI. Focus group discussions were transcribed and analyzed using an inductive and deductive thematic content approach. Five themes were identified: Enabling continuity of care; System design; Accessibility and services in the community; Transportation services; and Uncertainty about the provided services. The results of participants’ experiences contributed to developing recommendations of service provision for mobility, leading to a patient-centered continuum of rehabilitation services. Accessibility to rehabilitation to improve the quality of care by addressing needs during transitions and mobility-related deficits, providing needed information, coordinated care, and self-management support in the community.

Objective To compare the effects of interleukin 6 receptor blockers, tocilizumab and sarilumab, with or without corticosteroids, on mortality in patients with covid-19.Design Systematic review and network meta-analysis.Data sources World Health Organization covid-19 database, a comprehensive multilingual source of global covid-19 literature, and two prospective meta-analyses (up to 9 June 2021).Review methods Trials in which people with suspected, probable, or confirmed covid-19 were randomised to interleukin 6 receptor blockers (with or without corticosteroids), corticosteroids, placebo, or standard care. The analysis used a bayesian framework and assessed the certainty of evidence using the GRADE approach. Results from the fixed effect meta-analysis were used for the primary analysis.Results Of 45 eligible trials (20 650 patients) identified, 36 (19 350 patients) could be included in the network meta-analysis. Of 36 trials, 27 were at high risk of bias, primarily due to lack of blinding. Tocilizumab, in combination with corticosteroids, suggested a reduction in the risk of death compared with corticosteroids alone (odds ratio 0.79, 95% credible interval 0.70 to 0.88; 35 fewer deaths per 1000 people, 95% credible interval 52 fewer to 18 fewer per 1000; moderate certainty of evidence), as did sarilumab in combination with corticosteroids, compared with corticosteroids alone (0.73, 0.58 to 0.92; 43 fewer per 1000, 73 fewer to 12 fewer; low certainty). Tocilizumab and sarilumab, each in combination with corticosteroids, appeared to have similar effects on mortality when compared with each other (1.07, 0.86 to 1.34; eight more per 1000, 20 fewer to 35 more; low certainty). The effects of tocilizumab (1.12, 0.91 to 1.38; 20 more per 1000, 16 fewer to 59 more; low certainty) and sarilumab (1.07, 0.81 to 1.40; 11 more per 1000, 38 fewer to 55 more; low certainty), when used alone, suggested an increase in the risk of death.Conclusion These findings suggest that in patients with severe or critical covid-19, tocilizumab, in combination with corticosteroids, probably reduces mortality, and that sarilumab, in combination with corticosteroids, might also reduce mortality. Tocilizumab and sarilumab, in combination with corticosteroids, could have similar effectiveness. Tocilizumab and sarilumab, when used alone, might not be beneficial.

Abstract Background Mild traumatic brain injury (mTBI) is an increasing public health problem that can lead to persistent symptoms that have several functional consequences. Understanding the prognosis of a condition is an important component of clinical decision-making and can help guide the prevention of long-term disabilities of patients with mTBI. Several studies and systematic reviews have been conducted in order to understand prognosis of chronic symptoms following mTBI. We aim to synthesize evidence from systematic reviews on factors that affect the risk of persistent symptoms in mTBI-affected adults. Methods We will conduct an overview of systematic reviews following steps described in the Cochrane Handbook. We will search in Cochrane, Medline, CINAHL, Embase, PsycINFO, and Epistemonikos for systematic reviews about the prognosis of persistent symptoms following mTBI in the adult population. Two reviewers will independently screen all references and then select eligible reviews based on eligibility criteria. A data extraction grid will be used to extract relevant information. The risk of bias in the included reviews will be assessed using the ROBIS tool. Data will be synthesized into a comprehensive conceptual model in order to have a better understanding of the predictive factors of post-concussion symptoms following mTBI. Discussion Results will help multiple stakeholders, such as clinicians and rehabilitation program managers, to understand the prognosis of long-term consequences following mTBI. It could guide stakeholders to recognize their patients’ prognostic factors and to invest their time and resources in patients who need it the most. Systematic review registration PROSPERO CRD42020176676 .

Abstract Background High-dose vitamin C is increasingly used for sepsis and more recently for coronavirus disease 2019 (COVID-19) infections. Proponents argue that the low cost and near perfect safety profile of vitamin C support its early adoption. Yet, adverse events might be underreported and underappreciated. Case presentation We report a 73-year-old non-diabetic white man with end-stage renal disease on peritoneal dialysis admitted to the intensive care unit with septic shock that was suspected to be due to peritonitis. The patient was enrolled in LOVIT (Lessening Organ Dysfunction with VITamin C; ClinicalTrials.gov identifier: NCT03680274), a randomized placebo-controlled trial of high-dose intravenous vitamin C. He developed factitious hyperglycemia, as measured with a point-of-care glucometer, that persisted for 6 days after discontinuation of the study drug, confirmed to be vitamin C after unblinding. He also had short-lived iatrogenic coma because of hypoglycemia secondary to insulin administration. These events triggered a protocol amendment. Conclusions Although factitious hyperglycemia has been reported before using certain glucometers in patients treated with high-dose vitamin C, the persistence of this phenomenon for 6 days after the discontinuation of the therapy is a distinguishing feature. This case highlights the importance of monitoring glucose with a core laboratory assay for up to a week in specific populations, such as patients on peritoneal dialysis.

BackgroundSince the publication of the Convention on the Rights of Persons with Disabilities, several countries have adopted laws, policies, and action plans to improve the universal accessibility of environments to improve inclusion and social participation of all citizens. Different organizations are involved in the application of these measures. ObjectiveThe aim of this study is to identify strategies that are contextually appropriate and provide guidelines for organizations to promote successful implementation of universal accessibility. MethodsWe will conduct a scoping review identifying implementation strategies of universal accessibility measures in local organizations using the Arksey and O’Malley framework. We will search in Medline, CINHAL, Urban Studies Abstracts, ABI Inform, and Social Sciences Full Text from 2006 until today, following the adoption of the Convention on the Rights of Persons with Disabilities. Two reviewers will independently select studies for inclusion and will extract the data. A descriptive and thematic analysis of the characteristics of the identified implementation strategies will be performed. ResultsImplementation strategies will be summarized in tables. They will then be linked to various constructs and domains listed in the Theoretical Domain Framework to identify barriers and facilitators of organizations’ uptake of evidence-based strategies of implementation. ConclusionsWe will tabulate the characteristics of the included studies and the outcomes of implementation strategies in them. The results of this scoping review are expected to help the research community in various fields, local organizations, and stakeholders to identify better ways to improve implementation strategies of universal accessibility practices. International Registered Report Identifier (IRRID)PRR1-10.2196/33641

BackgroundRapid advances in technologies over the past 10 years have enabled large-scale biomedical and psychosocial rehabilitation research to improve the function and social integration of persons with physical impairments across the lifespan. The Biomedical Research and Informatics Living Laboratory for Innovative Advances of New Technologies (BRILLIANT) in community mobility rehabilitation aims to generate evidence-based research to improve rehabilitation for individuals with acquired brain injury (ABI). ObjectiveThis study aims to (1) identify the factors limiting or enhancing mobility in real-world community environments (public spaces, including the mall, home, and outdoors) and understand their complex interplay in individuals of all ages with ABI and (2) customize community environment mobility training by identifying, on a continuous basis, the specific rehabilitation strategies and interventions that patient subgroups benefit from most. Here, we present the research and technology plan for the BRILLIANT initiative. MethodsA cohort of individuals, adults and children, with ABI (N=1500) will be recruited. Patients will be recruited from the acute care and rehabilitation partner centers within 4 health regions (living labs) and followed throughout the continuum of rehabilitation. Participants will also be recruited from the community. Biomedical, clinician-reported, patient-reported, and brain imaging data will be collected. Theme 1 will implement and evaluate the feasibility of collecting data across BRILLIANT living labs and conduct predictive analyses and artificial intelligence (AI) to identify mobility subgroups. Theme 2 will implement, evaluate, and identify community mobility interventions that optimize outcomes for mobility subgroups of patients with ABI. ResultsThe biomedical infrastructure and equipment have been established across the living labs, and development of the clinician- and patient-reported outcome digital solutions is underway. Recruitment is expected to begin in May 2022. ConclusionsThe program will develop and deploy a comprehensive clinical and community-based mobility-monitoring system to evaluate the factors that result in poor mobility, and develop personalized mobility interventions that are optimized for specific patient subgroups. Technology solutions will be designed to support clinicians and patients to deliver cost-effective care and the right intervention to the right person at the right time to optimize long-term functional potential and meaningful participation in the community. International Registered Report Identifier (IRRID)PRR1-10.2196/12506

BackgroundThe LOVIT (Lessening Organ Dysfunction with Vitamin C) trial is a blinded multicenter randomized clinical trial comparing high-dose intravenous vitamin C to placebo in patients admitted to the intensive care unit with proven or suspected infection as the main diagnosis and receiving a vasopressor. ObjectiveWe aim to describe a prespecified statistical analysis plan (SAP) for the LOVIT trial prior to unblinding and locking of the trial database. MethodsThe SAP was designed by the LOVIT principal investigators and statisticians, and approved by the steering committee and coinvestigators. The SAP defines the primary and secondary outcomes, and describes the planned primary, secondary, and subgroup analyses. ResultsThe SAP includes a draft participant flow diagram, tables, and planned figures. The primary outcome is a composite of mortality and persistent organ dysfunction (receipt of mechanical ventilation, vasopressors, or new renal replacement therapy) at 28 days, where day 1 is the day of randomization. All analyses will use a frequentist statistical framework. The analysis of the primary outcome will estimate the risk ratio and 95% CI in a generalized linear mixed model with binomial distribution and log link, with site as a random effect. We will perform a secondary analysis adjusting for prespecified baseline clinical variables. Subgroup analyses will include age, sex, frailty, severity of illness, Sepsis-3 definition of septic shock, baseline ascorbic acid level, and COVID-19 status. ConclusionsWe have developed an SAP for the LOVIT trial and will adhere to it in the analysis phase. International Registered Report Identifier (IRRID)DERR1-10.2196/36261

AbstractObjectives To identify factors which may influence mobility and could be considered during the evaluation of mobility in individuals with acquired brain injury (ABI) following qualitative focus groups with both clinicians and individuals with ABI, to assess their needs and preferences in order to individualize their care management plans.Methods Five focus groups were held, three with clinicians from 3 rehabilitation sites of CRIR (CRDM: n = 4; IURDPM: n = 3; JRH: n = 10) and two with individuals with ABI from one rehabilitation site (CRDM) (individuals with stroke: n = 5; individuals with TBI: n = 5). Focus group discussions were transcribed and analyzed using inductive and deductive thematic content approaches.Results Four themes were identified: considering mobility holistically and individual needs, preferences, and unique experiences; assessment and intervention guidelines; support network; and uncertainty about symptoms and recovery. Using the ten-rule International Classification, Functioning, Disability, and Health framework linking process, codes were categorized into Body Functions Activity and Participation, and Environmental Factors exploring the prominent domains that mostly identify factors influencing mobility.Conclusions Comprehensive measurement of mobility remains an ongoing challenge owing to multiple contributing factors, ranging from personal and psychosocial factors to the influence of a myriad of environmental and community considerations. Preparing individuals with ABI for community mobility can be substantially improved if healthcare professionals employ communicative tools to facilitate shared decision making with patients and to deliver patient-centred rehabilitation care.

Abstract Background Patient prioritization is a strategy used to manage access to healthcare services. Patient prioritization tools (PPT) contribute to supporting the prioritization decision process, and to its transparency and fairness. Patient prioritization tools can take various forms and are highly dependent on the particular context of application. Consequently, the sets of criteria change from one context to another, especially when used in non-emergency settings. This paper systematically synthesizes and analyzes the published evidence concerning the development and challenges related to the validation and implementation of PPTs in non-emergency settings. Methods We conducted a systematic mixed studies review. We searched evidence in five databases to select articles based on eligibility criteria, and information of included articles was extracted using an extraction grid. The methodological quality of the studies was assessed by using the Mixed Methods Appraisal Tool. The article selection process, data extraction, and quality appraisal were performed by at least two reviewers independently. Results We included 48 studies listing 34 different patient prioritization tools. Most of them are designed for managing access to elective surgeries in hospital settings. Two-thirds of the tools were investigated based on reliability or validity. Inconclusive results were found regarding the impact of PPTs on patient waiting times. Advantages associated with PPT use were found mostly in relationship to acceptability of the tools by clinicians and increased transparency and equity for patients. Conclusions This review describes the development and validation processes of PPTs used in non-urgent healthcare settings. Despite the large number of PPTs studied, implementation into clinical practice seems to be an open challenge. Based on the findings of this review, recommendations are proposed to develop, validate, and implement such tools in clinical settings. Systematic review registration PROSPERO CRD42018107205

Introduction The COVID-19 pandemic and associated restrictive measures have caused important disruptions in economies and labour markets, changed the way we work and socialise, forced schools to close and healthcare and social services to reorganise. This unprecedented crisis forces individuals to make considerable efforts to adapt and will have psychological and social consequences, mainly on vulnerable individuals, that will remain once the pandemic is contained and will most likely exacerbate existing social and gender health inequalities. This crisis also puts a toll on the capacity of our healthcare and social services structures to provide timely and adequate care. The MAVIPAN (Ma vie et la pandémie/ My Life and the Pandemic) study aims to document how individuals, families, healthcare workers and health organisations are affected by the pandemic and how they adapt.Methods and analysis MAVIPAN is a 5-year longitudinal prospective cohort study launched in April 2020 across the province of Quebec (Canada). Quantitative data will be collected through online questionnaires (4–6 times/year) according to the evolution of the pandemic. Qualitative data will be collected with individual and group interviews and will seek to deepen our understanding of coping strategies. Analysis will be conducted under a mixed-method umbrella, with both sequential and simultaneous analyses of quantitative and qualitative data.Ethics and dissemination MAVIPAN aims to support the healthcare and social services system response by providing high-quality, real-time information needed to identify those who are most affected by the pandemic and by guiding public health authorities’ decision making regarding intervention and resource allocation to mitigate these impacts. MAVIPAN was approved by the Ethics Committees of the Primary Care and Population Health Research Sector of CIUSSS de la Capitale-Nationale (Committee of record) and of the additional participating institutions.Trial registration number NCT04575571.

BackgroundLiving labs in the health and well-being domain have become increasingly common over the past decade but vary in available infrastructure, implemented study designs, and outcome measures. The Horizon 2020 Project Virtual Health and Wellbeing Living Lab Infrastructure aims to harmonize living lab procedures and open living lab infrastructures to facilitate and promote research activities in the health and well-being domain in Europe and beyond. This protocol will describe the design of a joint research activity, focusing on the use of innovative technology for both rehabilitation interventions and data collection in a rehabilitation context. ObjectiveWith this joint research activity, this study primarily aims to gain insight into each living lab’s infrastructure and procedures to harmonize health and well-being living lab procedures and infrastructures in Europe and beyond, particularly in the context of rehabilitation. Secondarily, this study aims to investigate the potential of innovative technologies for rehabilitation through living lab methodologies. MethodsThis study has a mixed methods design comprising multiple phases. There are two main phases of data collection: cocreation (phase 1) and small-scale pilot studies (phase 2), which are preceded by a preliminary harmonization of procedures among the different international living labs. An intermediate phase further allows the implementation of minor adjustments to the intervention or protocol depending on the input that was obtained in the cocreation phase. A total of 6 small-scale pilot studies using innovative technologies for intervention or data collection will be performed across 4 countries. The target study sample comprises patients with stroke and older adults with mild cognitive impairment. The third and final phases involve Delphi procedures to reach a consensus on harmonized procedures and protocols. ResultsPhase 1 data collection will begin in March 2022, and phase 2 data collection will begin in June 2022. Results will include the output of the cocreation sessions, small-scale pilot studies, and advice on harmonizing procedures and protocols for health and well-being living labs focusing on rehabilitation. ConclusionsThe knowledge gained by the execution of this research will lead to harmonized procedures and protocols in a rehabilitation context for health and well-being living labs in Europe and beyond. In addition to the harmonized procedures and protocols in rehabilitation, we will also be able to provide new insights for improving the implementation of innovative technologies in rehabilitation. International Registered Report Identifier (IRRID)PRR1-10.2196/34537

BackgroundSevere infections are characterized by inflammation and oxidative damage. Ascorbic acid (vitamin C) administration may attenuate oxidative damage and, in turn, reduce vascular endothelial injury in pulmonary and systemic vasculature. ObjectiveWe aim to describe a protocol for a living systematic review that will evaluate the effectiveness and safety of parenteral vitamin C administration in adults with severe infections, including those with COVID-19. MethodsWe searched Ovid MEDLINE, Embase, CINAHL, the Centers for Disease Control and Prevention COVID-19 database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to March 30, 2021, for randomized controlled trials evaluating parenteral vitamin C versus no parenteral vitamin C in hospitalized adults with severe infection. Eligible studies will include at least 1 arm involving any dose of parenteral vitamin C alone or in combination with other cointerventions and at least 1 arm not involving parenteral vitamin C. The primary outcomes of interest will include in-hospital, 30-day, and 90-day mortality. Title and abstract screening, full-text screening, data extraction, and risk of bias evaluation via a modified Risk of Bias 2.0 tool will be conducted independently and in pairs. We will perform random effects modeling for meta-analyses, in which study weights will be generated by using the inverse variance method. We will assess certainty in effect estimates by using the Grading of Recommendations Assessment, Development and Evaluation methodology. Meta-analyses will be updated iteratively as new trial evidence becomes available. ResultsAmong the 1386 citations identified as of March 30, 2021, a total of 17 eligible randomized controlled trials have been identified as of September 2021. We are in the process of updating the search strategy and associated data analyses. ConclusionsThe results will be of importance to critical care physicians and hospitalists who manage severe infection and COVID-19 in daily practice, and they may directly inform international clinical guidance. Although our systematic review will incorporate the most recent trial evidence, ongoing trials may change our confidence in the estimates of effects, thereby necessitating iterative updates in the form of a living review. Trial RegistrationPROSPERO CRD42020209187; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=209187 International Registered Report Identifier (IRRID)RR1-10.2196/33989

BackgroundEngaging patients and the public in clinical practice guideline (CPG) development is believed to contribute significantly to guideline quality, but the advantages of the various co-design strategies have not been empirically compared, making it difficult to choose one strategy over another. ObjectiveThis pilot study aims to document the acceptability, feasibility, and outcomes of 2 methods of involving patients in outlining CPG. MethodsA single-blind crossover pragmatic study was performed with patients with traumatic brain injury. The patients experimented with 2 alternative methods of producing clinical practice recommendations (ie, a discussion group and a wiki). The participants rated the acceptability of the 2 methods, and feasibility was assessed using indicators, such as the number of participants who completed the 2 methods and the number of support interventions required. Experts, blinded to the method, independently rated the participants' outcome recommendations for clarity, accuracy, appropriateness, and usefulness. ResultsWe recruited 20 participants, and 16 completed the study. The acceptability of the 2 methods showed little variation, with qualitative comments expressing a slight preference for the social nature of focus groups. Thus, both methods of involving patients in CPG development appeared feasible, and the experts’ opinions of the adapted recommendations were both positive, although the recommendations produced through focus groups were deemed more relevant to support clinical practice. ConclusionsOur results confirm the acceptability and feasibility of focus groups and wikis to allow patients with traumatic brain injury to participate in clinical practice guideline production. This study contributes to the scientific literature by suggesting that the 2 methods were acceptable, feasible, and produced positive outcomes. Trial RegistrationClinicalTrials.gov NCT02023138; https://clinicaltrials.gov/ct2/show/NCT02023138

Parkinson’s disease (PD) is characterized by neurodegeneration and neuroinflammation. PD prevalence and incidence are higher in men than in women and modulation of gonadal hormones could have an impact on the disease course. This was investigated in male and female gonadectomized (GDX) and SHAM operated (SHAM) mice. Dutasteride (DUT), a 5α-reductase inhibitor, was administered to these mice for 10 days to modulate their gonadal sex hormones. On the fifth day of DUT treatment, mice received 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to model PD. We have previously shown in these mice the toxic effect of MPTP in SHAM and GDX males and in GDX females on dopamine markers and astrogliosis whereas SHAM females were protected by their female sex hormones. In SHAM males, DUT protected against MPTP toxicity. In the present study, microglial density and the number of doublets, representative of a microglial proliferation, were increased by the MPTP lesion only in male mice and prevented by DUT in SHAM males. A three-dimensional morphological microglial analysis showed that MPTP changed microglial morphology from quiescent to activated only in male mice and was not prevented by DUT. In conclusion, microgliosis can be modulated by sex hormone-dependent and independent factors in a mice model of PD.

Vaccination has saved billions of human lives and has considerably reduced the economic burden associated with pandemic and endemic infectious diseases. Notwithstanding major advancements in recent decades, multitude diseases remain with no available effective vaccine. While subunit-based vaccines have shown great potential to address the safety concerns of live-attenuated vaccines, their limited immunogenicity remains a major drawback that still needs to be addressed for their use fighting infectious illnesses, autoimmune disorders, and/or cancer. Among the adjuvants and delivery systems for antigens, bacterial proteinaceous supramolecular structures have recently received considerable attention. The use of bacterial proteins with self-assembling properties to deliver antigens offers several advantages, including biocompatibility, stability, molecular specificity, symmetrical organization, and multivalency. Bacterial protein nanoassemblies closely simulate most invading pathogens, acting as an alarm signal for the immune system to mount an effective adaptive immune response. Their nanoscale architecture can be precisely controlled at the atomic level to produce a variety of nanostructures, allowing for infinite possibilities of organized antigen display. For the bottom-up design of the proteinaceous antigen delivery scaffolds, it is essential to understand how the structural and physicochemical properties of the nanoassemblies modulate the strength and polarization of the immune responses. The present review first describes the relationships between structure and the generated immune responses, before discussing potential and current clinical applications.

Many endophytes and rhizobacteria associated with plants support the growth and health of their hosts. The vast majority of these potentially beneficial bacteria have yet to be characterized, in part because of the cost of identifying bacterial isolates. Matrix-assisted laser desorption-time of flight (MALDI-TOF) has enabled culturomic studies of host-associated microbiomes but analysis of mass spectra generated from plant-associated bacteria requires optimization. In this study, we aligned mass spectra generated from endophytes and rhizobacteria isolated from heritage and sweet varieties of Zea mays. Multiple iterations of alignment attempts identified a set of parameters that sorted 114 isolates into 60 coherent MALDI-TOF taxonomic units (MTUs). These MTUs corresponded to strains with practically identical (>99%) 16S rRNA gene sequences. Mass spectra were used to train a machine learning algorithm that classified 100% of the isolates into 60 MTUs. These MTUs provided >70% coverage of aerobic, heterotrophic bacteria readily cultured with nutrient rich media from the maize microbiome and allowed prediction of the total diversity recoverable with that particular cultivation method. Acidovorax sp., Pseudomonas sp. and Cellulosimicrobium sp. dominated the library generated from the rhizoplane. Relative to the sweet variety, the heritage variety c ontained a high number of MTUs. The ability to detect these differences in libraries, suggests a rapid and inexpensive method of describing the diversity of bacteria cultured from the endosphere and rhizosphere of maize.

NLRP3 inflammasome activation and complement-mediated inflammation have been implicated in promoting choroidal neovascularization (CNV) in age-related macular degeneration (AMD), but central questions regarding their contributions to AMD pathogenesis remain unanswered. Key open questions are (1) whether NLRP3 inflammasome activation mainly in retinal pigment epithelium (RPE) or rather in non-RPE cells promotes CNV, (2) whether inflammasome activation in CNV occurs via NLRP3 or also through NLRP3-independent mechanisms, and (3) whether complement activation induces inflammasome activation in CNV. Here we show in a neovascular AMD mouse model that NLRP3 inflammasome activation in non-RPE cells but not in RPE cells promotes CNV. We demonstrate that both NLRP3-dependent and NLRP3-independent inflammasome activation mechanisms induce CNV. Finally, we find that complement and inflammasomes promote CNV through independent mechanisms. Our findings uncover an unexpected role of non-NLRP3 inflammasomes for CNV and suggest that combination therapies targeting inflammasomes and complement may offer synergistic benefits to inhibit CNV.

Introduction Orthopaedic injuries affect almost 90% of trauma patients. A previous scoping review and expert consultation survey identified 15 potential low-value intra-hospital practices in the adult orthopaedic trauma population. Limiting the frequency of such practices could reduce adverse events, improve clinical outcomes and free up resources. The aim of this study is to synthesise the evidence on intra-hospital practices for orthopaedic injuries, previously identified as potentially of low value.Methods and analysis We will search Medline, Excerpta Medica Database (EMBASE), the Cochrane Central Register of Controlled Trials and Epistemonikos to identify systematic reviews, randomised controlled trials (RCTs), quasi-RCTs, cohort studies and case–control studies that evaluate selected practices according to a priori PICOS statements (Population–Intervention–Comparator–Outcome–Study design) . We will evaluate the methodological quality for systematic reviews using the Measurement Tool to Assess Systematic Reviews version 2 (AMSTAR-2). Risk of bias in original studies will be evaluated with the Cochrane revised tool for RCTs (RoB2) and with the risk of bias in non-randomised studies of interventions (ROBINS-I) tool. If for a given practice, more than two original studies on our primary outcome are identified, we will conduct meta-analysis using a random effects model and assess heterogeneity using the I2 index. We will assess credibility of evidence (I–IV) based on statistical significance, sample size, heterogeneity and bias as per published criteria.Ethics and dissemination Ethics approval is not required as original data will not be collected. Knowledge users from three level I trauma centres are involved in the design and conduct of the study in accordance with an integrated knowledge translation approach. Findings related to the rapid review will be available in May 2020. They will be presented to key stakeholders to inform discussions and raise awareness on low-value injury care. In addition, results will be disseminated in a peer-reviewed journal, at national and international scientific meetings and to healthcare associations.

Abstract Background Psychosocial job stressors, such as low control and high demands, have been found to influence the health and wellbeing of doctors. However, past research in this area has relied on cross-sectional data, which limits causal inferences about the influence of psychosocial job stressors on health. In this study, we examine this relationship longitudinally while also assessing whether the relationship between psychosocial job stressors and health is modified by gender. Methods The data source was seven annual waves of the Medicine in Australia: Balancing Employment and Life (MABEL) survey. The outcome was self-rated health (measured using the SF-12), and key exposures reflected job control, job demands, work-life balance variables, employment arrangements, and aggression experienced at work. We used longitudinal fixed and random effects regression models to assess within and between-person changes in health. Results Excessive job demands, low job control, feelings of not being rewarded at work, and work-life imbalance were associated with higher within-person odds of poorer self-rated health. Gender differences were apparent. For female doctors, work arrangements and work-life imbalance were associated with poorer self-rated health whilst task-based job stressors were associated with poorer self-rated health in male doctors. Conclusions These results suggest the importance of addressing adverse working environments among doctors. Trial registration Not applicable.

ObjectivesPrimary brain tumors are composed of tumor cells, neural/glial tissues, edema, and vasculature tissue. Conventional MRI has a limited ability to evaluate heterogeneous tumor pathologies. We developed a novel diffusion MRI-based method-Heterogeneity Diffusion Imaging (HDI)-to simultaneously detect and characterize multiple tumor pathologies and capillary blood perfusion using a single diffusion MRI scan.MethodsSeven adult patients with primary brain tumors underwent standard-of-care MRI protocols and HDI protocol before planned surgical resection and/or stereotactic biopsy. Twelve tumor sampling sites were identified using a neuronavigational system and recorded for imaging data quantification. Metrics from both protocols were compared between World Health Organization (WHO) II and III tumor groups. Cerebral blood volume (CBV) derived from dynamic susceptibility contrast (DSC) perfusion imaging was also compared with the HDI-derived perfusion fraction.ResultsThe conventional apparent diffusion coefficient did not identify differences between WHO II and III tumor groups. HDI-derived slow hindered diffusion fraction was significantly elevated in the WHO III group as compared with the WHO II group. There was a non-significantly increasing trend of HDI-derived tumor cellularity fraction in the WHO III group, and both HDI-derived perfusion fraction and DSC-derived CBV were found to be significantly higher in the WHO III group. Both HDI-derived perfusion fraction and slow hindered diffusion fraction strongly correlated with DSC-derived CBV. Neither HDI-derived cellularity fraction nor HDI-derived fast hindered diffusion fraction correlated with DSC-derived CBV.ConclusionsConventional apparent diffusion coefficient, which measures averaged pathology properties of brain tumors, has compromised accuracy and specificity. HDI holds great promise to accurately separate and quantify the tumor cell fraction, the tumor cell packing density, edema, and capillary blood perfusion, thereby leading to an improved microenvironment characterization of primary brain tumors. Larger studies will further establish HDI's clinical value and use for facilitating biopsy planning, treatment evaluation, and noninvasive tumor grading.

Measuring the proximity of the body to the environment has the potential to provide rehabilitation health care professionals (RHCP) new, additional information to assess mobility. The aims of this study were to explore the opinions and needs of professionals to use a new device to measure such proximity, and to determine potential barriers and facilitators to implement it within the clinical setting. Four focus groups were conducted with 23 RHCP. The concept of a proximity measurement device in the early stages of development was introduced. A qualitative content analysis using a model of clinical utility as guidance for coding of the transcribed texts was used. Many potential uses were raised including: improving patient safety, motor learning, independence in tasks as gait, transfers and reaching tasks, saving time during assessment, improving follow-up with the client, data precision and objectivity to assess tasks. Barriers were related to still unclear relevance, effectiveness, the added value of such a device, and time required for use. The development of a turnkey device with support to facilitate its implementation was seen to be positive. These focus groups provided important information to further identify potential uses of such a device and to help to decrease barriers to its implementation.

BACKGROUND:During the 2013-2016 West Africa Ebola outbreak, supportive care was the only non-experimental treatment option for patients with Ebola virus disease (EVD). However, providing care that would otherwise be routine for most clinical settings in the context of a highly contagious and lethal pathogen is much more challenging. The objective of this study was to document and deepen understanding of barriers to provision of supportive care in Ebola treatment units (ETUs) as perceived by those involved in care delivery during the outbreak. METHODS:This qualitative study consisted of 29 in-depth semi-structured interviews with stakeholders (decision-makers, physicians, nurses) involved in patient care delivery during the outbreak. Analysis consisted of interview debriefing and team-based transcript coding in NVivo10 software using thematic analysis. FINDINGS:Participants emphasized three interconnected barriers to providing high-quality supportive care during the outbreak: 1) lack of material and human resources in ETUs; 2) ETU organizational structure limiting the provision of supportive clinical care; and 3) delayed and poorly coordinated policies limiting the effectiveness of global and national responses. Participants also noted the ethical complexities of defining and enacting best clinical practices in low-income countries. They noted tension between, on one hand, scaling up minimal care and investing in clinical care preparedness to a level sustainable in West Africa and, on the other, providing a higher level of supportive care, which in low-resource health systems would require important investments. CONCLUSION:Our findings identified potentially modifiable barriers to the delivery of supportive care to patients with EVD in West Africa. Addressing these in the inter-outbreak period will be useful to improve patient care and outcomes during inevitable future outbreaks. Promoting community trust and engagement through long-term capacity building of the healthcare workforce and infrastructure would increase both health system resilience and ability to handle other outbreaks of emerging diseases.