The reliability of gait parameters captured via instrumented walkways: a systematic review and meta-analysis

Introduction: Electronic pressure-sensitive walkways are commonly available solutions to quantitatively assess gait parameters for clinical and research purposes. Many studies have evaluated their measurement properties in different conditions with variable findings. In order to be informed about the current evidence of their reliability for optimal clinical and scientific decision making, this systematic review provided a quantitative synthesis of the test-retest reliability and minimal detectable change of the captured gait parameters across different test conditions (single and cognitive dual-task conditions) and population groups. Evidence acquisition: A literature search was conducted in PubMed, Embase, and Scopus until November 2021 to identify articles that examined the test-retest reliability properties of the gait parameters captured by pressure-sensitive walkways (gait speed, cadence, stride length and time, double support time, base of support) in adult healthy individuals or patients. The methodological quality was rated using the "Consensus-based standards for the selection of health measurement instruments" checklist. Data were meta-analyzed on intraclass correlation coefficient to examine the test-retest relative reliability. Quantitative synthesis was performed for absolute reliability, examined by the weighted average of minimal detectable change values. Evidence synthesis: A total of 44 studies were included in this systematic review. The methodological quality was adequate in half of the included studies. The main finding was that pressure-sensitive walkways are reliable tools for objective assessment of spatial and temporal gait parameters both in singleand cognitive dual-task conditions. Despite few exceptions, the review identified intraclass correlation coefficient higher than 0.75 and minimal detectable change lower than 30%, demonstrating satisfactory relative and absolute reliability in all examined populations (healthy adults, elderly, patients with cognitive impairment, spinocerebellar ataxia type 14, Huntington's disease, multiple sclerosis, Parkinson's disease, rheumatoid arthritis, spinal cord injury, stroke or vestibular dysfunction). Conclusions: Current evidence suggested that, despite different populations and testing protocols used in the included studies, the test-retest reliability of the examined gait parameters was acceptable under single and cognitive dual-task conditions. Further high-quality studies with powered sample sizes are needed to examine the reliability findings of the currently understudied and unexplored pathologies and test conditions

Spiral drawing analysis with a smart ink pen to identify Parkinson's disease fine motor deficits

Introduction: Since the uptake of digitizers, quantitative spiral drawing assessment allowed gaining insight into motor impairments related to Parkinson's disease. However, the reduced naturalness of the gesture and the poor user-friendliness of the data acquisition hamper the adoption of such technologies in the clinical practice. To overcome such limitations, we present a novel smart ink pen for spiral drawing assessment, intending to better characterize Parkinson's disease motor symptoms. The device, used on paper as a normal pen, is enriched with motion and force sensors. Methods: Forty-five indicators were computed from spirals acquired from 29 Parkinsonian patients and 29 age-matched controls. We investigated between-group differences and correlations with clinical scores. We applied machine learning classification models to test the indicators ability to discriminate between groups, with a focus on model interpretability. Results: Compared to control, patients' drawings were characterized by reduced fluency and lower but more variable applied force, while tremor occurrence was reflected in kinematic spectral peaks selectively concentrated in the 4-7 Hz band. The indicators revealed aspects of the disease not captured by simple trace inspection, nor by the clinical scales, which, indeed, correlate moderately. The classification achieved 94.38% accuracy, with indicators related to fluency and power distribution emerging as the most important. Conclusion: Indicators were able to significantly identify Parkinson's disease motor symptoms. Our findings support the introduction of the smart ink pen as a time-efficient tool to juxtapose the clinical assessment with quantitative information, without changing the way the classical examination is performed

Video-based Goniometer Applications for Measuring Knee Joint Angles during Walking in Neurological Patients: A Validity, Reliability and Usability Study

: Easy-to-use evaluation of Range Of Motion (ROM) during walking is necessary to make decisions during neurological rehabilitation programs and during follow-up visits in clinical and remote settings. This study discussed goniometer applications (DrGoniometer and Angles - Video Goniometer) that measure knee joint ROM during walking through smartphone cameras. The primary aim of the study is to test the inter-rater and intra-rater reliability of the collected measurements as well as their concurrent validity with an electro-goniometer. The secondary aim is to evaluate the usability of the two mobile applications. A total of 22 patients with Parkinson's disease (18 males, age 72 (8) years), 22 post-stroke patients (17 males, age 61 (13) years), and as many healthy volunteers (8 males, age 45 (5) years) underwent knee joint ROM evaluations during walking. Clinicians and inexperienced examiners used the two mobile applications to calculate the ROM, and then rated their perceived usability through the System Usability Scale (SUS). Intraclass correlation coefficients (ICC) and correlation coefficients (corr) were calculated. Both applications showed good reliability (ICC > 0.69) and validity (corr > 0.61), and acceptable usability (SUS > 68). Smartphone-based video goniometers could be used to assess the knee ROM during walking in neurological patients, because of their acceptable degree of reliability, validity and usability

Autonomic cardiac profile in male and female healthcare professionals with and without preschoolers: differences evidenced by heart rate variability analysis

A reduced nocturnal cardiac vagal modulation has been observed in working women with preschoolers. Whether this adaptation also occurs in men remains an open question. The aim of this study was to analyze the cardiac autonomic profile of two groups of healthcare male professionals, one with and one without preschoolers, to be compared to females. Twenty-five working men with preschoolers (M_KID, age 35.41 ± 4.01 years) and 25 without (M_NOKID, 34.48 ± 6.00 years) were compared with 25 working women with preschoolers (W_KID, 37.7 ± 5.6 years) and 25 without (W_NOKID, 35.4 ± 7.2 years). A 24-h Holter electrocardiogram was performed for time and frequency domain analysis of the beat-to-beat variations of RR interval (RR) variability, during daytime (DAY) and nighttime (NIGHT). The power of RR variability in the high frequency band (HFRR) was considered as an index of cardiac vagal modulation. RR variability indices were similar in M_KID and M_NOKID during both DAY and NIGHT. In contrast, W_KID showed a reduced nocturnal HFRR compared to W_NOKID. The comparison of working men with and without preschoolers revealed no differences in the cardiac autonomic profile, in contrast with women. This suggests that sex and/or gender may represent a crucial factor in the cardiac neural control in the parental condition

Carriers of ADAMTS13 Rare Variants Are at High Risk of Life-Threatening COVID-19

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections. Carriers are reported to be asymptomatic. Exome analysis of about 3000 SARS-CoV-2 infected subjects of different severities, belonging to the GEN-COVID cohort, revealed the specific role of vWF cleaving enzyme ADAMTS13 (A disintegrin-like and metalloprotease with thrombospondin type 1 motif, 13). We report here that ultra-rare variants in a heterozygous state lead to a rare form of COVID-19 characterized by hyper-inflammation signs, which segregates in families as an autosomal dominant disorder conditioned by SARS-CoV-2 infection, sex, and age. This has clinical relevance due to the availability of drugs such as Caplacizumab, which inhibits vWF-platelet interaction, and Crizanlizumab, which, by inhibiting P-selectin binding to its ligands, prevents leukocyte recruitment and platelet aggregation at the site of vascular damage

Gain- and Loss-of-Function CFTR Alleles Are Associated with COVID-19 Clinical Outcomes

Carriers of single pathogenic variants of the CFTR (cystic fibrosis transmembrane conductance regulator) gene have a higher risk of severe COVID-19 and 14-day death. The machine learning post-Mendelian model pinpointed CFTR as a bidirectional modulator of COVID-19 outcomes. Here, we demonstrate that the rare complex allele [G576V;R668C] is associated with a milder disease via a gain-of-function mechanism. Conversely, CFTR ultra-rare alleles with reduced function are associated with disease severity either alone (dominant disorder) or with another hypomorphic allele in the second chromosome (recessive disorder) with a global residual CFTR activity between 50 to 91%. Furthermore, we characterized novel CFTR complex alleles, including [A238V;F508del], [R74W;D1270N;V201M], [I1027T;F508del], [I506V;D1168G], and simple alleles, including R347C, F1052V, Y625N, I328V, K68E, A309D, A252T, G542*, V562I, R1066H, I506V, I807M, which lead to a reduced CFTR function and thus, to more severe COVID-19. In conclusion, CFTR genetic analysis is an important tool in identifying patients at risk of severe COVID-19

Association of Toll-like receptor 7 variants with life-threatening COVID-19 disease in males: findings from a nested case-control study

Background: Recently, loss-of-function variants in TLR7 were identified in two families in which COVID-19 segregates like an X-linked recessive disorder environmentally conditioned by SARS-CoV-2. We investigated whether the two families represent the tip of the iceberg of a subset of COVID-19 male patients.Methods: This is a nested case-control study in which we compared male participants with extreme phenotype selected from the Italian GEN-COVID cohort of SARS-CoV-2-infected participants (<60y, 79 severe cases versus 77 control cases). We applied the LASSO Logistic Regression analysis, considering only rare variants on young male subsets with extreme phenotype, picking up TLR7 as the most important susceptibility gene.Results: Overall, we found TLR7 deleterious variants in 2.1% of severely affected males and in none of the asymptomatic participants. The functional gene expression profile analysis demonstrated a reduction in TLR7-related gene expression in patients compared with controls demonstrating an impairment in type I and II IFN responses.Conclusion: Young males with TLR7 loss-of-function variants and severe COVID-19 represent a subset of male patients contributing to disease susceptibility in up to 2% of severe COVID-19

A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

: The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10-8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10-8). A total of 113 variants were associated with survival at P-value < 1.0 × 10-5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways

An explainable model of host genetic interactions linked to COVID-19 severity

We employed a multifaceted computational strategy to identify the genetic factors contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing (WES) dataset of a cohort of 2000 Italian patients. We coupled a stratified k-fold screening, to rank variants more associated with severity, with the training of multiple supervised classifiers, to predict severity based on screened features. Feature importance analysis from tree-based models allowed us to identify 16 variants with the highest support which, together with age and gender covariates, were found to be most predictive of COVID-19 severity. When tested on a follow-up cohort, our ensemble of models predicted severity with high accuracy (ACC = 81.88%; AUCROC = 96%; MCC = 61.55%). Our model recapitulated a vast literature of emerging molecular mechanisms and genetic factors linked to COVID-19 response and extends previous landmark Genome-Wide Association Studies (GWAS). It revealed a network of interplaying genetic signatures converging on established immune system and inflammatory processes linked to viral infection response. It also identified additional processes cross-talking with immune pathways, such as GPCR signaling, which might offer additional opportunities for therapeutic intervention and patient stratification. Publicly available PheWAS datasets revealed that several variants were significantly associated with phenotypic traits such as "Respiratory or thoracic disease", supporting their link with COVID-19 severity outcome.A multifaceted computational strategy identifies 16 genetic variants contributing to increased risk of severe COVID-19 infection from a Whole Exome Sequencing dataset of a cohort of Italian patients

Host genetics and COVID-19 severity: increasing the accuracy of latest severity scores by Boolean quantum features

The impact of common and rare variants in COVID-19 host genetics has been widely studied. In particular, in Fallerini et al. (Human genetics, 2022, 141, 147–173), common and rare variants were used to define an interpretable machine learning model for predicting COVID-19 severity. First, variants were converted into sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. After that, the Boolean features, selected by these logistic models, were combined into an Integrated PolyGenic Score (IPGS), which offers a very simple description of the contribution of host genetics in COVID-19 severity. IPGS leads to an accuracy of 55%–60% on different cohorts, and, after a logistic regression with both IPGS and age as inputs, it leads to an accuracy of 75%. The goal of this paper is to improve the previous results, using not only the most informative Boolean features with respect to the genetic bases of severity but also the information on host organs involved in the disease. In this study, we generalize the IPGS adding a statistical weight for each organ, through the transformation of Boolean features into “Boolean quantum features,” inspired by quantum mechanics. The organ coefficients were set via the application of the genetic algorithm PyGAD, and, after that, we defined two new integrated polygenic scores ((Formula presented.) and (Formula presented.)). By applying a logistic regression with both IPGS, ((Formula presented.) (or indifferently (Formula presented.)) and age as inputs, we reached an accuracy of 84%–86%, thus improving the results previously shown in Fallerini et al. (Human genetics, 2022, 141, 147–173) by a factor of 10%