Machine Learning in Falls Prediction; A cognition-based predictor of falls for the acute neurological in-patient population

Background Information: Falls are associated with high direct and indirect costs, and significant morbidity and mortality for patients. Pathological falls are usually a result of a compromised motor system, and/or cognition. Very little research has been conducted on predicting falls based on this premise. Aims: To demonstrate that cognitive and motor tests can be used to create a robust predictive tool for falls. Methods: Three tests of attention and executive function (Stroop, Trail Making, and Semantic Fluency), a measure of physical function (Walk-12), a series of questions (concerning recent falls, surgery and physical function) and demographic information were collected from a cohort of 323 patients at a tertiary neurological center. The principal outcome was a fall during the in-patient stay (n = 54). Data-driven, predictive modelling was employed to identify the statistical modelling strategies which are most accurate in predicting falls, and which yield the most parsimonious models of clinical relevance. Results: The Trail test was identified as the best predictor of falls. Moreover, addition of any others variables, to the results of the Trail test did not improve the prediction (Wilcoxon signed-rank p < .001). The best statistical strategy for predicting falls was the random forest (Wilcoxon signed-rank p < .001), based solely on results of the Trail test. Tuning of the model results in the following optimized values: 68% (+- 7.7) sensitivity, 90% (+- 2.3) specificity, with a positive predictive value of 60%, when the relevant data is available. Conclusion: Predictive modelling has identified a simple yet powerful machine learning prediction strategy based on a single clinical test, the Trail test. Predictive evaluation shows this strategy to be robust, suggesting predictive modelling and machine learning as the standard for future predictive tools

Health related quality of life in COVID-19 survivors discharged from acute hospitals: results of a short-form 36-item survey [version 1; peer review: awaiting peer review]

Background: Health-related quality of life (HRQL) is important for evaluating the impact of a disease in the longer term across the physical and psychological domains of human functioning. The aim of this study is to evaluate HRQL in COVID-19 survivors in Italy using the short form 36-items questionnaire (SF-36). Methods: This is an observational study involving adults discharged home following a coronavirus disease 2019 (COVID-19)-related hospital admission. Baseline demographic and clinical data including the Cumulative Illness Rating Scale (CIRS) and the Hospital Anxiety and Depression Scale (HADS) were collected. The validated Italian version of SF-36 was administered cross-sectionally. The SF-36 contains eight scales measuring limitations in physical and social functioning, the impact on roles and activities, fatigue, emotional wellbeing, pain and general health perception. Results: A total of 35 patients, with a mean age of 60 years, completed the SF-36. The results showed difficulties across the physical and psychological domains, particularly affecting the return to previous roles and activities. A higher burden of co-morbidities as well as a more severe muscle weakness was associated to a lower physical functioning. Younger age, rather than older, correlated to a perceived greater limitation in physical functioning and vitality. Conclusions: COVID-19 survivors particularly the ones of working age may need support for resuming their premorbid level of functioning and returning to work

The Trail Making test : a study of its ability to predict falls in the acute neurological in-patient population

Objective: To determine whether tests of cognitive function and patient-reported outcome measures of motor function can be used to create a machine learning-based predictive tool for falls. Design: Prospective cohort study. Setting: Tertiary neurological and neurosurgical center. Subjects: In all, 337 in-patients receiving neurosurgical, neurological, or neurorehabilitation-based care. Main Measures: Binary (Y/N) for falling during the in-patient episode, the Trail Making Test (a measure of attention and executive function) and the Walk-12 (a patient-reported measure of physical function). Results: The principal outcome was a fall during the in-patient stay (n = 54). The Trail test was identified as the best predictor of falls. Moreover, addition of other variables, did not improve the prediction (Wilcoxon signed-rank P < 0.001). Classical linear statistical modeling methods were then compared with more recent machine learning based strategies, for example, random forests, neural networks, support vector machines. The random forest was the best modeling strategy when utilizing just the Trail Making Test data (Wilcoxon signed-rank P < 0.001) with 68% (± 7.7) sensitivity, and 90% (± 2.3) specificity. Conclusion: This study identifies a simple yet powerful machine learning (Random Forest) based predictive model for an in-patient neurological population, utilizing a single neuropsychological test of cognitive function, the Trail Making test

Specific Recognition of the Viral Protein UL18 by CD85j/LIR-1/ILT2 on CD8+ T Cells Mediates the Non-MHC-Restricted Lysis of Human Cytomegalovirus-Infected Cells

Abstract Immune evasion mechanisms of human CMV are known; however, the immune control of infection remains poorly elucidated. We show that interaction between the viral protein UL18 on infected cells and the invariant receptor CD85j/LIR-1/ILT2 expressed on CTL is relevant for the control of infection. Resting and activated CD8+ T cells lysed UL18 expressing cells, whereas cells infected with CMV defective for UL18 were not killed. Lysis was not dependent on CD8+ T cell Ag specificity, MHC-unrestricted and specifically blocked by anti-CD85j and anti-UL18 mAb. Moreover, soluble recombinant UL18Fc immunoprecipitated CD85j from T cells. Activation is mediated by CD85j and its pathway is unrelated to CD3/TCR engagement. UL18 is detected in immunocompromised patients with productive infection and the mechanism used in vivo by human CMV to ensure survival of the immunocompetent host may be mediated by activation signals delivered by infected cells to T lymphocytes via UL18/CD85j interactions

CTLA4CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus

Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed

Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in mice coinfected with Strongyloides venezuelensis

The presence of intestinal helminths can down-regulate the immune response required to control mycobacterial infection. BALB/c mice infected with Mycobacterium bovis following an infection with the intestinal helminth Strongyloides venezuelensis showed reduced interleukin-17A production by lung cells and increased bacterial burden. Also, small granulomas and a high accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in the lung. These data suggest that intestinal helminth infection could have a detrimental effect on the control of tuberculosis (TB) and render coinfected individuals more susceptible to the development of TB

Safety and immunogenicity of radiation-attenuated PfSPZ vaccine in equatoguinean infants, children, and adults

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults /= 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine