Minimal detectable change of gait and balance measures in older neurological patients: estimating the standard error of the measurement from before-after rehabilitation data thanks to the linear mixed-effects models.

BACKGROUND: Tracking gait and balance impairment in time is paramount in the care of older neurological patients. The Minimal Detectable Change (MDC), built upon the Standard Error of the Measurement (SEM), is the smallest modification of a measure exceeding the measurement error. Here, a novel method based on linear mixed-effects models (LMMs) is applied to estimate the standard error of the measurement from data collected before and after rehabilitation and calculate the MDC of gait and balance measures. METHODS: One hundred nine older adults with a gait impairment due to neurological disease (66 stroke patients) completed two assessment sessions before and after inpatient rehabilitation. In each session, two trials of the 10-meter walking test and the Timed Up and Go (TUG) test, instrumented with inertial sensors, have been collected. The 95% MDC was calculated for the gait speed, TUG test duration (TTD) and other measures from the TUG test, including the angular velocity peak (ωpeak) in the TUG test's turning phase. Random intercepts and slopes LMMs with sessions as fixed effects were used to estimate SEM. LMMs assumptions (residuals normality and homoscedasticity) were checked, and the predictor variable ln-transformed if needed. RESULTS: The MDC of gait speed was 0.13 m/s. The TTD MDC, ln-transformed and then expressed as a percentage of the baseline value to meet LMMs' assumptions, was 15%, i.e. TTD should be < 85% of the baseline value to conclude the patient's improvement. ωpeak MDC, also ln-transformed and expressed as the baseline percentage change, was 25%. CONCLUSIONS: LMMs allowed calculating the MDC of gait and balance measures even if the test-retest steady-state assumption did not hold. The MDC of gait speed, TTD and ωpeak from the TUG test with an inertial sensor have been provided. These indices allow monitoring of the gait and balance impairment, which is central for patients with an increased falling risk, such as neurological old persons. TRIAL REGISTRATION: NA.

Italian translation and cultural adaptation of the Agitated Behavior Scale (ABS-I) in patients with acquired brain injuries.

OBJECTIVE: The objective of this study was to produce a cross-cultural adaptation in Italian of the Agitated Behavior Scale (ABS), originally developed in English, as the first of two stages that also include cross-cultural validation and allow a clinical scale to be used in the proper setting such as rehabilitation units. METHODS: In order to adapt the ABS scale to a different cultural environment, five consecutive steps were performed: (1) forward translations (n = 8), (2) synthesis of the 8 forward translations to obtain a first shared italian version (ABS_I_trial), (3) back translations (n = 3), (4) creation of an expert committee to evaluate forward and back translations and finally (5) the cognitive debriefing. RESULTS: After the five steps, including forward translations and back translations, the process of committee verification and judgement and the evaluative step of cognitive debriefing, high comprehensibility of all items was found, resulting in an Italian translation version of ABS suitable for application in a clinical setting. CONCLUSION: ABS translation was produced by means of a standardized procedure aimed at minimizing cross-cultural gaps. The expert committee evaluated the version produced as highly understandable in Italian. Further steps, such as the subsequent validation of its psychometric properties, are needed to employ this translation in a clinical setting.

Physical and Rehabilitation Medicine: say relational or functional, not holistic.

Modern medicine tends to privilege disciplines promising "objective" laws governing body parts (from molecules to organs). Studies on a person's illness and disability are (apparently) confined to "subjectivity." The Specialty of Physical and Rehabilitation Medicine is often regarded as a humanitarian approach, belonging at best to the family of "soft," "qualitative," or "quasi-experimental" sciences. This specialty often claims specificity by labelling itself as "functional" and "holistic." However, it is shown here that the former term is acceptable, yet redundant, and the second misleading. When human behaviors and perceptions are at stake, "function" indicates a person's relationship with the outer world (already tackled by the definitional term "physical" from the Greek "physis"). The word "holistic" emphasizes mind-body unity and person-environment interdependence but, in current usage, overshadows the complementary need for an analytic, experimental approach to any function. Medicine aims at fighting disease and disability in single persons. This endeavor requires knowing body parts and mechanisms and understanding how interventions on "parts" affect the "whole." This understanding rests on the experimental method. For instance, returning to a given societal role (participation) may require restoration of walking (activity), which may require reinforcement of weakened muscular groups (impairment). Working only on holistic bio-psycho-social "wholes" may miss the therapeutic mission of medicine.

Fatigue may improve equally after balance and endurance training in multiple sclerosis: a randomised, crossover clinical trial.

Introduction: Fatigue and poor balance are frequent and severe problems in multiple sclerosis (MS) that may interact. Endurance training is known to be effective on fatigue. This study aims to test if balance training is more effective against MS fatigue. Methods: A randomised crossover trial was run, recruiting 31 MS people (21 women; median age: 46 years, range: 30-64; median EDSS: 4, range: 2.5-5). Participants received balance and endurance training alternately (15 one-to-one sessions, 5 days/week) and were assessed before (T0), after (T1), and 30 days after treatment ended (T2). The Modified Fatigue Impact Scale (MFIS) with scores linearised through Rasch analysis was the primary outcome (the lower the measure, the better the condition, i.e., the lower the fatigue symptoms). The Equiscale balance scale and posturography (EquiTest) were used to assess balance. Linear mixed-effects models with ANOVA were used for significance testing. Results: Thirteen participants had no carryover effect and were included in the primary analysis. Fatigue significantly changed across the three time points (F2,58 = 16.0; p < 0.001), but no difference across treatments was found. Altogether, both treatments significantly improved the MFIS measure at T1 (95%CI: -1.24 logits; mean: -1.67 to -0.81 logits) and T2 (95%CI: -1.04; mean: -1.49 to -0.60) compared to T0 (95%CI: -0.51; mean: -0.95 to -0.08; p ≤ 0.001). Equiscale and posturography highlighted balance improvement after balance training but not after endurance training. Conclusion: Balance and endurance training could similarly reduce fatigue in MS patients in the short term. However, only balance training also improved balance in MS.

Interpreting results from Rasch analysis 1. The "most likely" measures coming from the model.

Purpose: The present article summarises the characteristics of Rasch's theory, providing an original metrological model for persons' measurements. Properties describing the person "as a whole" are key outcome variables in Medicine. This is particularly true in Physical and Rehabilitation Medicine, targeting the person's interaction with the outer world. Such variables include independence, pain, fatigue, balance, and the like. These variables can only be observed through behaviours of various complexity, deemed representative of a given "latent" person's property. So how to infer its "quantity"? Usually, behaviours (items) are scored ordinally, and their "raw" scores are summed across item lists (questionnaires). The limits and flaws of scores (i.e., multidimensionality, non-linearity) are well known, yet they still dominate the measurement in Medicine.Conclusions: Through Rasch's theory and statistical analysis, scores are transformed and tested for their capacity to respect fundamental measurement axioms. Rasch analysis returns the linear measure of the person's property ("ability") and the item's calibrations ("difficulty"), concealed by the raw scores. The difference between a person's ability and item difficulty determines the probability that a "pass" response is observed. The discrepancy between observed scores and the ideal measures (i.e., the residual) invites diagnostic reasoning. In a companion article, advanced applications of Rasch modelling are illustrated. Implications for rehabilitationQuestionnaires' ordinal scores are poor approximations of measures. The Rasch analysis turns questionnaires' scores into interval measures, provided that its assumptions are respected.Thanks to the Rasch analysis, accurate measures of independence, pain, fatigue, cognitive capacities and other whole person's variables of paramount importance in rehabilitation are available.The current work is addressed to rehabilitation professionals looking for an introduction to interpreting published results based on Rasch analysis.The first of a series of two, the present article illustrates the most common graphic and numeric outputs found in published papers presenting the Rasch analysis of questionnaires.

Interpreting results from Rasch analysis 2. Advanced model applications and the data-model fit assessment.

Purpose: The present paper presents developments and advanced practical applications of Rasch's theory and statistical analysis to construct questionnaires for measuring a person's traits. The flaws of questionnaires providing raw scores are well known. Scores only approximate objective, linear measures. The Rasch Analysis allows you to turn raw scores into measures with an error estimate, satisfying fundamental measurement axioms (e.g., unidimensionality, linearity, generalizability). A previous companion article illustrated the most frequent graphic and numeric representations of results obtained through Rasch Analysis. A more advanced description of the method is presented here.Conclusions: Measures obtained through Rasch Analysis may foster the advancement of the scientific assessment of behaviours, perceptions, skills, attitudes, and knowledge so frequently faced in Physical and Rehabilitation Medicine, not less than in social and educational sciences. Furthermore, suggestions are given on interpreting and managing the inevitable discrepancies between observed scores and ideal measures (data-model "misfit"). Finally, twelve practical take-home messages for appraising published results are provided.Implications for rehabilitationThe current work is the second of two papers addressed to rehabilitation clinicians looking for an in-depth introduction to the Rasch analysis.The first paper illustrates the most common results reported in published papers presenting the Rasch analysis of questionnaires.The present article illustrates more advanced applications of the Rasch analysis, also frequently found in publications.Twelve take-home messages are given for a critical appraisal of the results.

Pay attention: you can fall! The Mini-BESTest scale and the turning duration of the TUG test provide valid balance measures in neurological patients: a prospective study with falls as the balance criterion.

Background: Balance, i.e., the ability not to fall, is often poor in neurological patients and this impairment increases their risk of falling. The Mini-Balance Evaluation System Test (Mini-BESTest), a rating scale, the Timed Up and Go (TUG) test, and gait measures are commonly used to quantify balance. This study assesses the criterion validity of these measures as balance measures. Methods: The probability of being a faller within nine months was used as the balance criterion. The Mini-BESTest, TUG (instrumented with inertial sensors), and walking test were administered before and after inpatient rehabilitation. Multiple and LASSO logistic regressions were used for the analysis. The diagnostic accuracy of the model was assessed with the area under the curve (AUC) of the receiver operating characteristic curve. Mobility measure validity was compared with the Akaike Information Criterion (AIC). Results: Two hundred and fourteen neurological patients (stroke, peripheral neuropathy, or parkinsonism) were recruited. In total, 82 patients fell at least once in the nine-month follow-up. The Mini-BESTest (AUC = 0.69; 95%CI: 0.62-0.76), the duration of the TUG turning phase (AUC = 0.69; 0.62-0.76), and other TUG measures were significant faller predictors in regression models. However, only the turning duration (AIC = 274.0) and Mini-BESTest (AIC = 276.1) substantially improved the prediction of a baseline model, which only included fall risk factors from the medical history (AIC = 281.7). The LASSO procedure selected gender, disease chronicity, urinary incontinence, the Mini-BESTest, and turning duration as optimal faller predictors. Conclusion: The TUG turning duration and the Mini-BESTest predict the chance of being a faller. Their criterion validity as balance measures in neurological patients is substantial.

The social relevance and the temporal constraints of motor resonance in humans.

In humans, motor resonance effects can be tracked by measuring the enhancement of corticospinal excitability by action observation. Uncovering factors driving motor resonance is crucial for optimizing action observation paradigms in experimental and clinical settings. In the present study, we deepen motor resonance properties for grasping movements. Thirty-five healthy subjects underwent an action observation task presenting right-hand grasping movements differing from their action goal. Single-pulse transcranial magnetic stimulation was applied over the left primary motor cortex at 100, 200, or 300 ms from the onset of the visual stimulus depicting the action. Motor-evoked potentials were recorded from four muscles of the right hand and forearm. Results show a muscle-specific motor resonance effect at 200 ms after movement but selectively for observing a socially relevant grasp towards another human being. This effect correlates with observers' emotional empathy scores, and it was followed by inhibition of motor resonance at 300 ms post-stimulus onset. No motor resonance facilitation emerged while observing intransitive hand movement or object grasping. This evidence highlights the social side of motor resonance and its dependency on temporal factors.

Measuring Quality of Life in Adults with Scoliosis: A Cross-Sectional Study Comparing SRS-22 and ISYQOL Questionnaires.

Idiopathic scoliosis is common in adulthood and can impact patients' physical and psychological health. The Scoliosis Research Society-22 Questionnaire (SRS-22) has been designed to assess health-related quality of life (HRQOL) in idiopathic scoliosis, and it is the most used disease-specific outcome tool from adolescence to adulthood. More recently, the Italian Spine Youth Quality of Life (ISYQOL) international questionnaire was developed, which performs better than SRS-22 in adolescent spinal deformities. However, the ISYQOL questionnaire has never been tested in adults. This study compares the construct validity of ISYQOL and SRS-22 with the Rasch analysis (partial credit model). We recruited 150 adults and 50 adolescents with scoliosis (≥30° Cobb). SRS-22, but not ISQYOL, showed disordered categories and one item not fitting the Rasch model. A 21-item SRS-22 version with revised categories was arranged and further compared to ISYQOL. Both questionnaires showed multidimensionality, and some items (SRS-22 in a greater number) functioned differently in persons of different ages. However, the artefacts caused by multidimensionality and differential functioning had a low impact on the questionnaires' measures. The construct validity of ISYQOL International and the revised SRS-22 are comparable. Both questionnaires (but not the original SRS-22) can return measures of disease burden in adults with scoliosis.

Long COVID in Children: A Multidisciplinary Review.

Long COVID syndrome has emerged as a long-lasting consequence of acute SARS-CoV-2 infection in adults. In addition, children may be affected by Long COVID, with potential clinical issues in different fields, including problems in school performance and daily activities. Yet, the pathophysiologic bases of Long COVID in children are largely unknown, and it is difficult to predict who will develop the syndrome. In this multidisciplinary clinical review, we summarise the latest scientific data regarding Long COVID and its impact on children. Special attention is given to diagnostic tests, in order to help the physicians to find potential disease markers and quantify impairment. Specifically, we assess the respiratory, upper airways, cardiac, neurologic and motor and psychological aspects. Finally, we also propose a multidisciplinary clinical approach.

Reversed Mirror Therapy (REMIT) after Stroke-A Proof-of-Concept Study.

In mirror training (MIT), stroke patients strive to move their hands while looking at the reflected image of the unaffected one. The recruitment of the mirror neurons and visual-proprioceptive conflict are expected to facilitate the paretic voluntary movement. Here, a reversed MIT (REMIT) is presented, which requires moving hands while looking at the reflected image of the paretic one, giving the illusion of being unable to move the unimpaired hand. This study compares MIT and REMIT on post-stroke upper-limb recovery to gain clues on the mechanism of action of mirror therapies. Eight chronic stroke patients underwent two weeks of MIT and REMIT (five sessions each) in a crossover design. Upper-limb Fugl-Meyer, Box and Block and handgrip strength tests were administered at baseline and treatments end. The strength of the mirror illusion was evaluated after each session. MIT induced a larger illusory effect. The Fugl-Meyer score improved to the same extent after both treatments. No changes occurred in the Box and Block and the handgrip tests. REMIT and MIT were equally effective on upper-limb dexterity, challenging the exclusive role of mirror neurons. Contrasting learned nonuse through an intersensory conflict might provide the rationale for both forms of mirror-based rehabilitation after stroke.

Cervical Proprioception Assessed through Targeted Head Repositioning: Validation of a Clinical Test Based on Optoelectronic Measures.

Neck proprioception is commonly assessed with head repositioning tests. In such a test, an operator rotates the head of a blindfolded individual to a target position. After returning to the rest position, the participant actively repositions the head to the target. Joint Position Error (JPE) is the angular difference between the target angle (however oriented in a 3D space) and the actively reached positions (the smaller the difference, the better the proprioception). This study aimed to validate a head-to-target (HTT) repositioning test using an optoelectronic system for also measuring the components of the JPE in the horizontal, frontal, and sagittal planes. The head movements requested by the operator consisted of 30° left-right rotations and 25° flexion-extension. The operators or subjects could not obtain these movements without modest rotations in other planes. Two operators were involved. Twenty-six healthy participants (13 women) were recruited (mean (SD): 33.4 (6.3) years). The subjects' JPE in the requested (intended) plane of motion (JPEint-component) was a few degrees only and smaller for flexion-extensions than for left-right rotations (right rotation: 5.39° (5.29°); left rotation: 5.03° (4.51°), extension: 1.79° (3.94°); flexion: 0.54° (4.35°)). Participants' average error in unintended planes was around 1° or less. Inter-operator consistency and agreement were high. The smallest detectable change, at p < 0.05, for JPEint-component ranged between 4.5° and 6.98°. This method of optoelectronic measurement in HTT repositioning tests provides results with good metric properties, fostering application to clinical studies.

Cross-cultural validation of the Italian Spine Youth Quality of Life questionnaire: the ISYQOL international.

BACKGROUND: Adolescent idiopathic scoliosis and its treatments can severely impact health-related quality of life. The Italian Spine Youth Quality of Life (ISYQOL) questionnaire, initially developed in Italian and tested on Italian people, was created to measure quality of life in young persons with spine changes. ISYQOL was created using the Rasch analysis, a modern psychometric technique for questionnaires' assessment and development, which showed that the ordinal scores of the ISYQOL Italian version provide sound quality of life measures. AIM: The current work aims to evaluate the cross-cultural equivalence of the ISYQOL questionnaire in seven different countries. DESIGN: Cross-sectional, international, multi-centre study. SETTING: Outpatient clinic. POPULATION: Five hundred fifty persons with adolescent idiopathic scoliosis from English Canada, French Canada, Greece, Italy, Spain, Poland, and Türkiye. METHODS: The ISYQOL Italian version was translated into six languages with the forward-backwards procedure. The conceptual equivalence of the items' content was verified, and any inconsistency was resolved by consensus. The Rasch analysis was used here to evaluate that ISYQOL translations retained the good measurement properties of the Italian version of the questionnaire. In addition, the Differential Item Functioning (DIF) was checked to assess the psychometric equivalence of the ISYQOL items in patients from different countries. RESULTS: Four items of the translated ISYQOL were dropped from the questionnaire since they did not contribute to measuring due to their poor fit to the model of Rasch. Seven items were affected by DIF for nationality, a finding pointing out that these items do not work the same (i.e. are not equivalent) in the different countries. Thanks to the Rasch analysis, the DIF for nationality was amended, and ISYQOL International was eventually obtained. CONCLUSIONS: ISYQOL International returns interval quality of life measures in people with adolescent idiopathic scoliosis with high cross-cultural equivalence in the tested countries. CLINICAL REHABILITATION IMPACT: Rigorous testing showed that ISYQOL International ordinal scores return quality of life measures cross-culturally equivalent in English and French Canada, Greece, Italy, Spain, Poland, and Türkiye. A new, psychometrically sound patient-reported outcome measure is thus available in rehabilitation medicine to measure health-related quality of life in idiopathic scoliosis.

Action Observation Treatment for Upper Limb Rehabilitation in Patients With Stroke: Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: In the last few years, new noninvasive strategies have emerged as rehabilitative treatments for patients with stroke. Action observation treatment (AOT) is a rehabilitation approach based on the properties of the mirror neuron system with a positive impact on modifying cortical activation patterns and improving the upper limb kinematics. AOT involves the dynamic process of observing purposeful actions with the intention of imitating and then practicing those actions. In recent years, several clinical studies suggested the effectiveness of AOT in patients with stroke to improve motor recovery and autonomy in activities of daily living. However, a deeper knowledge of the behavior of the sensorimotor cortex during AOT seems to be essential. OBJECTIVE: The aim of this clinical trial, conducted in 2 neurorehabilitation centers and in patients' homes, is to investigate the effectiveness of AOT in patients with stroke, confirming the translational power of a tailored treatment. Particular emphasis will be placed on the predictive value of neurophysiological biomarkers. In addition, the feasibility and impact of a home-based AOT program will be investigated. METHODS: A 3-arm, assessor-blinded, randomized controlled trial will be performed by enrolling patients with stroke in the chronic stage. A total of 60 participants will be randomly allocated to receive 15 sessions of AOT with different protocols (AOT at the hospital, AOT at home, and sham AOT), 3 sessions per week. The primary outcome will be assessed using the Fugl-Meyer Assessment-Upper Extremity scores. Secondary outcomes will be clinical, biomechanical, and neurophysiological assessment. RESULTS: The study protocol is part of a project (project code GR-2016-02361678) approved and funded by the Italian Ministry of Health. The study began with the recruitment phase in January 2022, and enrollment was expected to end in October 2022. Recruitment is now closed (December 2022). The results of this study are expected to be published in spring 2023. Upon completion of the analyses, we will examine the preliminary effectiveness of the intervention and neurophysiological outcomes. CONCLUSIONS: This study will be used to evaluate the effectiveness of 2 different AOT scenarios (ie, AOT at the hospital and AOT at home) in patients with chronic stroke and to assess the predictive value of neurophysiological biomarkers. Specifically, we will attempt to induce the functional modification of the cortical components by exploiting the features of the mirror neuron system, demonstrating relevant clinical, kinematic, and neurophysiological changes after AOT. With our study, we also want to provide, for the first time in Italy, the AOT home-based program while assessing its feasibility and impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT04047134; https://clinicaltrials.gov/ct2/show/NCT04047134. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42094.

Differential Item Functioning of the Mini-BESTest Balance Measure: A Rasch Analysis Study.

The Mini-Balance Evaluation Systems Test (Mini-BESTest), a 14-item scale, has high content validity for balance assessment. This study further examines the construct validity of the Mini-BESTest with an emphasis on its measurement invariance. The Mini-BESTest was administered to 292 neurological patients in two sessions (before and after rehabilitation) and evaluated with the Rasch analysis (Many-Facet Rating Scale Model: persons, items, sessions). Categories' order and fit to the model were assessed. Next, maps, dimensionality, and differential item functioning (DIF) were examined for construct validity evaluation. DIF was inspected for several clinically important variables, including session, diagnosis, and assistive devices. Mini-BESTest items had ordered categories and fitted the Rasch model. The item map did not flag severe construct underrepresentation. The dimensionality analysis showed that another variable extraneous to balance affected the score of a few items. However, this multidimensionality had only a modest impact on measures. Session did not cause DIF. DIF for assistive devices affected six items and caused a severe measurement artefact. The measurement artefact caused by DIF for diagnosis was negligible. The Mini-BESTest returns interval measures with robust construct validity and measurement invariance. However, caution should be used when comparing Mini-BESTest measures obtained with and without assistive devices.

The Rasch Analysis Shows Poor Construct Validity and Low Reliability of the Quebec User Evaluation of Satisfaction with Assistive Technology 2.0 (QUEST 2.0) Questionnaire.

This study aims to test the construct validity and reliability of the Quebec User Evaluation of Satisfaction with assistive Technology 2.0 (QUEST)-device, an eight-item questionnaire for measuring satisfaction with assistive devices. We collected 250 questionnaires from 79 patients and 32 caregivers. One QUEST was completed for each assistive device. Five assistive device types were included. QUEST was tested with the Rasch analysis (Many-Facet Rating Scale Model: persons, items, and device type). Most patients were affected by neurological disabilities, and most questionnaires were about mobility devices. All items fitted the Rasch model (InfitMS range: 0.88-1.1; OutfitMS: 0.84-1.28). However, the ceiling effect of the questionnaire was large (15/111 participants totalled the maximum score), its targeting poor (respondents mean measure: 1.90 logits), and its reliability was 0.71. The device classes had different calibrations (range: -1.18 to 1.26 logits), and item 3 functioned differently in patients and caregivers. QUEST satisfaction measures have low reliability and weak construct validity. Lacking invariance, the QUEST total score is unsuitable for comparing the satisfaction levels of users of different device types. The differential item functioning suggests that the QUEST could also be problematic for comparing satisfaction in patients and caregivers.

Why Questionnaire Scores Are Not Measures: A Question-Raising Article.

ABSTRACT: Any person is provided by characteristics that can be neither located in body parts nor directly observed (so-called latent variables): these may be behaviors, attitudes, perceptions, motor and cognitive skills, knowledge, emotions, and the like. Physical and rehabilitation medicine frequently faces variables of this kind, the target of many interventions. Latent variables can only be observed through representative behaviors (e.g., walking for independence, moaning for pain, social isolation for depression, etc.). To measure them, behaviors are often listed and summated as items in cumulative questionnaires ("scales"). Questionnaires ultimately provide observations ("raw scores") with the aspect of numbers. Unfortunately, they are only a rough and often misleading approximation to true measures for various reasons. Measures should satisfy the same measurement axioms of physical sciences. In the article, the flaws hidden in questionnaires' scores are summarized, and their consequences in outcome assessment are highlighted. The report should inspire a critical attitude in the readers and foster the interest in modern item response theory, with reference to Rasch analysis.

Balance impairment in myotonic dystrophy type 1: Dynamic posturography suggests the coexistence of a proprioceptive and vestibular deficit.

Falls are frequent in Myotonic Dystrophy type 1 (DM1), but the pathophysiology of the balance impairment needs further exploration in this disease. The current work aims to provide a richer understanding of DM1 imbalance. Standing balance in 16 patients and 40 controls was tested in two posturographic tests (EquiTest™). In the Sensory Organization Test (SOT), standstill balance was challenged by combining visual (eyes open vs. closed) and environmental conditions (fixed vs. sway-tuned platform and/or visual surround). In the "react" test, reflexes induced by sudden shifts in the support base were studied. Oscillations of the body centre of mass (COM) were measured. In the SOT, COM sway was larger in patients than controls in any condition, including firm support with eyes open (quiet standing). On sway-tuned support, COM oscillations when standing with closed eyes were larger in patients than controls even after taking into account the oscillations with eyes open. In the "react" paradigm, balance reflexes were delayed in patients. Results in both experimental paradigms (i.e., SOT and react test) are consistent with leg muscle weakness. This, however, is not a sufficient explanation. The SOT test highlighted that patients rely on vision more than controls to maintain static balance. Consistently enough, evidence is provided that an impairment of proprioceptive and vestibular systems contributes to falls in DM1. Rehabilitation programs targeted at reweighting sensory systems may be designed to improve safe mobility in DM1.

HLA Allele Frequencies and Association with Severity of COVID-19 Infection in Northern Italian Patients.

HLA allelic distribution was analysed in a cohort of 96 Northern Italian subjects (53M/43F) (mean age 59.9 ± 13.3 years) from Lombardy who developed COVID-19 during the first two pandemic waves to investigate possible correlations between HLA molecules and disease severity. An important role of HLA- B and HLA-C loci in modulating the clinical severity of COVID-19 disease was identified. In particular, the HLA-B07 supertype was observed to be associated with a significant risk for severe disease; conversely, the HLA-B27 supertype and C*12:02 allele played a protective role as they were associated with milder disease. These associations were confirmed after applying a multinomial regression analysis to adjust the correlation for age, gender and comorbidities with COVID-19 severity. Though the power of results is limited by the small sample size, data herein contribute to shedding light on the role played by genetic background in COVID-19 infection.