Embodied Spatial Navigation Training in Mild Cognitive Impairment: A Proof-of-Concept Trial.

Background: Egocentric and allocentric spatial memory impairments affect the navigation abilities of older adults with mild cognitive impairment (MCI). Embodied cognition research hints that specific aids can be implemented into virtual reality (VR) training to enhance spatial memory. Objective: In this study, we preliminarily tested 'ANTaging', an embodied-based immersive VR training for egocentric and allocentric memory, compared to treatment as usual (TAU) spatial training in MCI. Methods: MCI patients were recruited for this controlled trial. A cognitive battery was administered at pre-test, after ten sessions of ANTaging or TAU intervention, and at 3-month follow-up (FU). The primary outcomes were spatial cognition tests (Corsi supra-span, CSS; Manikin test, MT). VR egocentric and allocentric performance was also collected. Results: We found that ANTaging significantly improved MT scores at FU compared to TAU. CSS slightly improved in both groups. Concerning secondary outcomes, auditory-verbal forgetting significantly improved at post-test in the ANTaging but not TAU group and significantly declined at FU in the TAU but not in the ANTaging group. Global cognition significantly improved at FU for TAU and remained stable for ANTaging. Other tests showed no improvement or deterioration. Clinical significance showed that ANTaging is effective for CSS. Virtual egocentric and allocentric memory performance improved across ANTaging sessions. Conclusions: ANTaging holds the potential to be superior for improving spatial cognition in MCI compared to TAU. Embodied cognition research provides insights for designing effective spatial navigation rehabilitation in aging.

Bodily and Visual-Cognitive Navigation Aids to Enhance Spatial Recall in Mild Cognitive Impairment.

Background: Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. Objective: We aimed to assess navigation cues for innovative spatial training in aging. Methods: Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Results: Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. Conclusions: These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded.

Beyond traditional training: Integrating data from semi-immersive VR dual-task intervention in Parkinsonian Syndromes. A study protocol.

Completing cognitive and motor tasks simultaneously requires a high level of cognitive control in terms of executive processes and attentional abilities. Most of the daily activities require a dual-task performance. While walking, for example, it may be necessary to adapt gait to obstacles of the environment or simply participate in a conversation; all these activities involve more than one ability at the same time. This parallel performance may be critical in the cognitive or motor load, especially for patients with neurological diseases such as Parkinsonian Syndromes. Patients are often characterized by a crucial impairment in performing both tasks concurrently, showing a decrease in attention skills and executive functions, thus leading to increased negative outcomes. In this scenario, the accurate assessment of the components involved in dual-task performance is crucial, and providing an early specific training program appears to be essential. The objective of this protocol is to assess cognitive and motor components involved in dual-task performance and create a training program based on ecological activities focusing on executive and motor functions. Thus, we will employ Virtual Reality to provide semi-immersive, multisensory, ecological, standardized, and realistic experiences for rehabilitative purposes in patients with Parkinsonian Syndromes, considering its high prevalence in aging and the incidence of motor and cognitive dysfunctions in this population. Moreover, we propose to integrate the great amount of different data provided by dual-task and Virtual Reality system, using machine learning techniques. These integrations may increase the treatment's reliability in terms of better prognostic indexes and individualized training.

Corrigendum: The effects of an acceptance and commitment-informed interdisciplinary rehabilitation program for chronic airway diseases on health status and psychological symptoms.

[This corrects the article DOI: 10.3389/fpsyg.2021.818659.].

Usability of an Embodied CAVE System for Spatial Navigation Training in Mild Cognitive Impairment.

Individuals with mild cognitive impairment (MCI) usually report navigation and spatial memory impairments. Spatial navigation is an embodied process that requires the active involvement of both physical (e.g., motor commands and proprioception) and cognitive (e.g., decision-making and mental rotation) information. Immersive virtual reality (IVR) is a valuable tool that employs this information as real-world navigation does. Given the crucial impact of spatial navigation on daily life, research should focus on ways to enhance it. Though they are still in their development, contemporary IVR methods for spatial navigation training in MCI seem promising. In this usability study, eight patients with MCI syndrome tested an IVR spatial navigation training demo and interacted with the CAVE using active stereo glasses, a foot-motion pad, and a joypad. During the demo, users were asked to report their impressions on the IVR training using the thinking-aloud procedure. Moreover, questionnaires regarding usability, presence and cybersickness were administered at the end of the experience. Our results show that the first version of this system is usable by the patients even if most of them did not have experience with PC/IVR. The system provided a moderate sense of spatial presence and limited negative effects. Issues found during the thinking-aloud procedure concerned the visual aspects, which affected the interaction user-system. Participants reported that they needed more practice with the foot-motion pad even though the overall experience was positively evaluated. Identifying these critical features was essential to develop an improved version of the current system.

Enhancing spatial navigation skills in mild cognitive impairment patients: a usability study of a new version of ANTaging software.

Introduction: Mild Cognitive Impairment (MCI) often presents challenges related to spatial navigation and retention of spatial information. Navigating space involves intricate integration of bodily and environmental cues. Spatial memory is dependent on two distinct frame of reference systems for organizing this information: egocentric and allocentric frames of reference. Virtual Reality (VR) has emerged as a promising technology for enhancing spatial navigation skills and spatial memory by facilitating the manipulation of bodily, environmental, and cognitive cues. Methods: This usability study was based on a fully within-subjects design in which seven MCI patients underwent two kinds of VR conditions: participants were required to complete the ANTaging demo both in Oculus Rift S (immersive condition) and in Samsung UHD 4K monitor (semi-immersive condition). Participants were seated and they had to use a foot-motion pad to navigate and explore the environment to collect and relocate some objects in the virtual environment. Post-interaction, users provided feedback on their experiences. Additionally, usability, potential side effects, data analysis feasibility, and user preferences with immersive and semi-immersive technologies were assessed through questionnaires. Results: Results indicated higher usability ratings for the semi-immersive setup, with fewer negative effects reported compared to the immersive counterpart. According to qualitative analyses of the interviews, patients do seem to like both VR apparatuses even though the semi-immersive condition was perceived as the most suitable choice because of the size of the screen. Patients generally found it difficult to remember object locations. Participants expressed the need for more practice with the foot-motion pad, despite an overall positive experience. They generally would like to use this system to improve their memory. Discussion: Identifying these key aspects was crucial for refining the system before the upcoming clinical trial. This study sheds light on the potential of semi-immersive VR in aiding individuals with MCI, paving the way for enhanced spatial navigation interventions.

Contribution of cognitive and bodily navigation cues to egocentric and allocentric spatial memory in hallucinations due to Parkinson's disease: A case report.

Parkinson's disease (PD) manifestations can include visual hallucinations and illusions. Recent findings suggest that the coherent integration of bodily information within an egocentric representation could play a crucial role in these phenomena. Egocentric processing is a key aspect of spatial navigation and is supported by the striatum. Due to the deterioration of the striatal and motor systems, PD mainly impairs the egocentric rather than the allocentric spatial frame of reference. However, it is still unclear the interplay between spatial cognition and PD hallucinations and how different navigation mechanisms can influence such spatial frames of reference. We report the case of A.A., a patient that suffers from PD with frequent episodes of visual hallucinations and illusions. We used a virtual reality (VR) navigation task to assess egocentric and allocentric spatial memory under five navigation conditions (passive, immersive, map, path decision, and attentive cues) in A.A. and a PD control group without psychosis. In general, A.A. exhibited a statistically significant classical dissociation between the egocentric and allocentric performance with a greater deficit for the former. In particular, the dissociation was statistically significant in the "passive" and "attentive cues" conditions. Interestingly in the "immersive" condition, the dissociation was not significant and, in contrast to the other conditions, trends showed better performance for egocentric than allocentric memory. Within the theories of embodiment, we suggest that body-based information, as assessed with VR navigation tasks, could play an important role in PD hallucinations. In addition, the possible neural underpinnings and the usefulness of VR are discussed.

Brain M-App's Structure and Usability: A New Application for Cognitive Rehabilitation at Home.

Cognitive frailty is defined as a clinical condition characterized by both physical frailty and cognitive impairment, without reaching the criteria for dementia. The major goal of rehabilitation intervention is to assist patients in performing ordinary personal duties without the assistance of another person, or at the very least to remove the need for additional support, using adaptive approaches and facilities. In this regard, home-based rehabilitation allows patients to continue an intervention begun in a hospital setting while also ensuring support and assistance when access to healthcare systems is limited, such as during the present pandemic situation. We thus present Brain m-App, a tablet-based application designed for home-based cognitive rehabilitation of frail subjects, addressing spatial memory, attention, and executive functions. This app exploits the potential of 360° videos which are well-suited to home-based rehabilitation. The Brain m-app is made up of 10 days of activities that include a variety of exercises. The activities were chosen based on those patients used to do during their clinical practice in the hospital with the aim to improve their independence and autonomy in daily tasks. The preliminary usability test, which was conducted on five older people, revealed a sufficient level of usability, however, the sample size was modest. Results from the clinical study with 10 patients, revealed that Brain m-App improved especially executive functions and memory performances.

The Effects of an Acceptance and Commitment-Informed Interdisciplinary Rehabilitation Program for Chronic Airway Diseases on Health Status and Psychological Symptoms.

BACKGROUND: Chronic airway diseases are prevalent and costly conditions. Interdisciplinary rehabilitation programs that include Acceptance and Commitment-based (ACT) components could be important to tackle the vicious circle linking progression of the disease, inactivity, and psychopathological symptoms. METHODS: A retrospective evaluation of routinely collected data of an interdisciplinary rehabilitation program was performed. The program included group sessions including patient education, breathing exercise, occupational therapy and an ACT-based psychological treatment, and individual sessions of physical therapy. Demographic data, clinical characteristics of the patients and the values of outcome variables (health status, quality of life, anxiety, and depression) before treatment, at discharge, at 3 months, and at 6 months were extracted from medical records. Multiple imputation was employed to address missing data. Linear mixed models were employed to assess changes over time. Multivariable logistic regression was performed to assess predictors of a minimum clinically important change of health status from baseline to the 6-months follow-up. RESULTS: Data from 31 patients with chronic obstructive pulmonary disease (COPD) and 12 patients with bronchiectasis were extracted. Health status improved from baseline to discharge to the 3 months follow-up, but not to the 6 months follow-up. Anxiety and depression improved across all the time points. Quality of life did not improve over time. Having a worse health status at baseline and fewer depressive symptoms were significantly associated with achieving a minimum clinically important change of health status at 6 months. The effects of the interdisciplinary program were not different for patients with COPD or with bronchiectasis. DISCUSSION: Interdisciplinary programs including ACT-based components are promising treatments for the rehabilitation of patients with chronic airway diseases.

Executive Functions Are Associated with Fall Risk but not Balance in Chronic Cerebrovascular Disease.

BACKGROUND: Older people's deficits in executive functions (EF) have been shown to lead to higher fall risk, postural sway, and reduced speed. Crucially, EF impairments are even more pronounced in individuals with chronic cerebrovascular disease (CVD), namely vascular cognitive impairment. METHODS: In this retrospective cross-sectional study, we used a complete neuropsychological battery, including the Trail Making Test (TMT) and physical measures, such as the Morse fall and EQUI scales, to assess 66 individuals with chronic CVD. Linear regressions, Bayesian analyses, and model selection were performed to see the impact of EF, global cognition, and vascular parkinsonism/hemiplegia on physical measures (fall risk and balance). RESULTS: The TMT part B and BA correlated (r = 0.44 and r = 0.45) with Morse fall scale. Only EF significantly explained fall risk, whereas global cognition and vascular parkinsonism/hemiplegia did not. These findings were confirmed by Bayesian evidence and parsimony model selection. Balance was not significantly correlated with any of the neuropsychological tests. CONCLUSIONS: This is the first study investigating the relationship between cognitive and physical measures in a sample of older people with chronic CVD. The results are consistent with previous findings that link EF with fall risk in CVD.

Usability Issues of Clinical and Research Applications of Virtual Reality in Older People: A Systematic Review.

Aging is a condition that may be characterized by a decline in physical, sensory, and mental capacities, while increased morbidity and multimorbidity may be associated with disability. A wide range of clinical conditions (e.g., frailty, mild cognitive impairment, metabolic syndrome) and age-related diseases (e.g., Alzheimer's and Parkinson's disease, cancer, sarcopenia, cardiovascular and respiratory diseases) affect older people. Virtual reality (VR) is a novel and promising tool for assessment and rehabilitation in older people. Usability is a crucial factor that must be considered when designing virtual systems for medicine. We conducted a systematic review with Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines concerning the usability of VR clinical systems in aging and provided suggestions to structure usability piloting. Findings show that different populations of older people have been recruited to mainly assess usability of non-immersive VR, with particular attention paid to motor/physical rehabilitation. Mixed approach (qualitative and quantitative tools together) is the preferred methodology; technology acceptance models are the most applied theoretical frameworks, however senior adapted models are the best within this context. Despite minor interaction issues and bugs, virtual systems are rated as usable and feasible. We encourage usability and user experience pilot studies to ameliorate interaction and improve acceptance and use of VR clinical applications in older people with the aid of suggestions (VR-USOP) provided by our analysis.

An Immersive Motor Protocol for Frailty Rehabilitation.

Frailty is a pre-clinical condition that worsens physical health and quality of life. One of the most frequent symptoms of frailty is an increased risk of falling. In order to reduce this risk, we propose an innovative virtual reality motor rehabilitation program based on an immersive tool. All exercises will take place in the CAVE, a four-screen room with a stationary bike. The protocol will include two types of exercises for the improvement of balance: "Positive Bike" and "Avoid the Rocks." We will choose evaluation scales related to the functional aspects and subjective perception of balance. Our aim is to prove that our innovative motor rehabilitation protocol is as effective as or more effective than classical rehabilitation.

A Social Virtual Reality-Based Application for the Physical and Cognitive Training of the Elderly at Home.

Frailty is a clinical condition affecting the elderly population which results in an increased risk of falls. Previous studies demonstrated that falls prevention programs are effective, but they suffer from low adherence, especially when subjects have to train unsupervised in their homes. To try to improve treatment adherence, virtual reality and social media have been proposed as promising strategies for the increase of users' motivation and thus their willingness to practice. In the context of smart homes, this work presents SocialBike, a virtual reality-based application aimed at improving the clinical outcomes of older frail adults in their houses. Indeed, SocialBike is integrated in the "house of the future" framework and proposes a Dual Task training program in which the users are required to cycle on a stationary bike while recognizing target animals or objects appearing along the way. It also implements the possibility of training with other users, thus reducing the risk of social isolation. Within SocialBike, users can choose the multiplayer mode they prefer (i.e., collaborative or competitive), and are allowed to train following their own attitude. SocialBike's validation, refinement, and business model are currently under development, and are briefly discussed as future works.

Characteristics, Usability, and Users Experience of a System Combining Cognitive and Physical Therapy in a Virtual Environment: Positive Bike.

We present the architecture and usability evaluation of virtual reality system-"Positive Bike"-designed for improving cognitive and motor conditions in frail elderly patients. The system consists of a cycle-ergometer integrated in an immersive virtual reality system (CAVE) which allows combining motor and cognitive exercises according to a "dual-task" paradigm. We tested the usability and user's experience of the prototype in a pilot evaluation study that involved five elderly patients. The prototype was tested in one-session training to understand the limitations and areas for improvement of our system. The evaluation consisted in (i) usability assessment using the system usability scale; (ii) evaluation of user's engagement using the flow state scale; and (iii) expert evaluation involving interviews with domain experts. Results showed a good usability, both for system usability scale and the semi-structured interview. The level of flow (i.e., enjoyment with the task at hand) measured using the short flow state scale, was also high. Analysis of semi-structured interview carried out with domain experts provided further indications to improve the system. Overall, these findings show that, despite some limitations, the system is usable and provides an enjoyable user's experience.

A wearable remote monitoring system for the identification of subjects with a prolonged QT interval or at risk for drug-induced long QT syndrome.

BACKGROUND: A correct measurement of the QT interval in the out-of-hospital setting is important whenever the long QT syndrome (LQTS) is suspected or a therapy might lead to drug-induced LQTS (diLQTS) because QT interval monitoring in the initial days of therapy could alert to dangerous QT prolongation. We explored whether automated QTc measurements (BGM) by BodyGuardian™ (BG), a wearable remote monitoring system, are sufficiently reliable compared to our own manual measurements (MM) performed on the same beats during 12­lead Holter recordings in LQTS patients (pts) and in healthy controls. METHODS: We performed 351 measurements in 20 LQTS pts and 16 controls. MM and BGM were compared by a Bland-Altman plot (BAp). High values of BAp indicate large differences between measurements. RESULTS: In all 36 subjects QTc was 446 ±â€¯41 and 445 ±â€¯47 ms in MM and BGM, respectively. The mean ±â€¯SE BAp was -1.4 ±â€¯1.8 ms for QTc in all subjects, 8.3 ±â€¯2.3 and -7.2 ±â€¯2.5 ms respectively in controls and LQTS. The disagreement between BGM and MM <15 ms in all, in controls, and in LQTS was respectively 57%, 63% and 54%. Among controls, there were only 3/132 false positive measurements (BGM QTc >470 ms when MM QTc <440 ms) in 3 different subjects. Among LQTS, there were 10/219 false negative measurements (BGM QTc <440 ms when MM QTc >470 ms) in 6 pts, but only two had multiple false negative values. CONCLUSIONS: This wearable monitoring system reliably identifies a prolonged QT interval and probably also subjects at risk for diLQTS.

For neonatal ECG screening there is no reason to relinquish old Bazett's correction.

Aims: There is an almost endless controversy regarding the choice of the QT correction formula to be used in electrocardiograms (ECG) in neonates for screening for long QT syndrome (LQTS). We compared the performance of four commonly used formulae and a new formula derived from neonates. Methods and results: From a cohort of 44 596 healthy neonates prospectively studied in Italy between 2001 and 2006, 5000 ECGs including 17 with LQTS-causing mutation identified by genotyping were studied using four QT correction formulae [Bazett's (QTcB), Fridericia's (QTcF), Framingham (QTcL), and Hodges (QTcH)]. A neonate-specific exponential correction (QTcNeo) was derived using 2500 randomly selected ECGs and validated for accuracy in the remaining 2500 ECGs. Digital ECGs were recorded between the 15th and 25th day of life; QT interval was measured manually in leads II, V5, and V6. To assess the ability to provide heart rate (HR) independent QT correction, regression analysis of the QTc-HR plots for all 5000 ECGs with each correction formula was done. QTcB provided the most HR independent correction with a slope closest to zero (slope +0.086 ms/b.p.m.) followed by QTcF (slope -0.308 ms/b.p.m.), QTcL (slope -0.364 ms/b.p.m.), and QTcH (slope +0.962 ms/b.p.m.). The QTc-HR slope of QTcNeo (QT/RR0.467) was similar to QTcB. The ability to correctly identify neonates with LQTS was best with QTcB, QTcF, and QTcNeo (comparable areas under the receiver operating characteristic curves) with positive predictive value of 39-40% and sensitivity of 100%. Cut-off values were 460 ms for QTcB, 394 ms for QTcF, and 446 ms for QTcNeo. Conclusions: The Bazett's correction provides an effective HR independent QT correction and also accurately identifies the neonates affected by LQTS. It can be used with confidence in neonates, although other methods could also be used with appropriate cut-offs.

QT interval and dispersion in drug-free anorexia nervosa adolescents: a case control study.

Long QT values have been reported in patients with anorexia nervosa of the restricting type (ANr) potentially increasing the risk of fatal arrhythmia, especially if psychotropic drug treatment is required. Nevertheless, the previous studies on this topic are biased by drug exposure, long disease durations, and small sample sizes. This study is aimed at assessing QTc and QTcd values in ANr adolescents with recent onset and drug free, as compared to subjects affected by psychiatric disorders other than ANr. We evaluated QTc and its dispersion (QTcd) in a population of 77 drug-free ANr female adolescents and compared to an equal number of healthy controls (H-CTRL) and pathological controls (P-CTRL, mixed psychiatric disorders). The QT determination was performed on a standard simultaneous 12-lead ECG in blind by a single experienced investigator. QTc was calculated by the Bazett's formula and QTcd was determined as the difference between the maximum and minimum QTc intervals in different leads. Only for ANr patients, clinico-demographic data, hormones, and electrolytes were obtained. QTc was slightly reduced in ANr patients (27.7 ms, < 10%, p < 0.0003) vs. controls, while QTcd was increased in P-CTRL (30%, p < 0.0003). Heart rate was significantly lower in ANr patients vs. controls (25%; p < 0.003). Tyroid hormones and serum potassium showed weak although significant positive correlations with QTc in ANr patients. QTcd displayed a weak negative correlation with the BMI percentile (r = - 0.262, p = 0.03). We reject the hypothesis that QTc and QTcd are increased in drug-free ANr adolescents with a relatively short-disease duration. Further studies are needed to understand if the previously reported increase might be related to other associated chronic disorders, such as hormonal or electrolyte imbalance.

A Novel Virtual Reality-Based Training Protocol for the Enhancement of the "Mental Frame Syncing" in Individuals with Alzheimer's Disease: A Development-of-Concept Trial.

A growing body of evidence suggests that people with Alzheimer's Disease (AD) show compromised spatial abilities. In addition, there exists from the earliest stages of AD a specific impairment in "mental frame syncing," which is the ability to synchronize an allocentric viewpoint-independent representation (including object-to-object information) with an egocentric one by computing the bearing of each relevant "object" in the environment in relation to the stored heading in space (i.e., information about our viewpoint contained in the allocentric viewpoint-dependent representation). The main objective of this development-of-concept trial was to evaluate the efficacy of a novel VR-based training protocol focused on the enhancement of the "mental frame syncing" of the different spatial representations in subjects with AD. We recruited 20 individuals with AD who were randomly assigned to either "VR-based training" or "Control Group." Moreover, eight cognitively healthy elderly individuals were recruited to participate in the VR-based training in order to have a different comparison group. Based on a neuropsychological assessment, our results indicated a significant improvement in long-term spatial memory after the VR-based training for patients with AD; this means that transference of improvements from the VR-based training to more general aspects of spatial cognition was observed. Interestingly, there was also a significant effect of VR-based training on executive functioning for cognitively healthy elderly individuals. In sum, VR could be considered as an advanced embodied tool suitable for treating spatial recall impairments.

No Untoward Effect of Long-Term Ketoconazole Administration on Electrocardiographic QT Interval in Patients with Cushing's Disease.

Ketoconazole is listed among drugs that prolong QT interval and may increase the risk of torsade de pointes, a severe ventricular arrhythmia. This compound has recently been approved for treatment of Cushing's syndrome, a severe endocrine disorder. These patients harbour several risk factors for prolonged QT interval, for example hypokalaemia and left ventricular hypertrophy, but no study has evaluated whether administration of ketoconazole affects their QT interval. The aim of this study was to assess the QT interval in patients with Cushing's disease during long-term administration of ketoconazole. Electrocardiograms from 15 patients with Cushing's disease (12 women, 3 men, age: 37.8 ± 2.66 years) on ketoconazole treatment (100 mg-800 mg qd) for 1 month to 12 years were reviewed retrospectively. QT interval was measured and corrected for heart rate (QTc). Measurements before and during ketoconazole treatment were compared and any abnormal QTc value recorded. Concurrent medical therapies were also documented. On average, QTc was superimposable before and during ketoconazole treatment (393.2 ± 7.17 versus 403.3 ± 6.05 msec. in women; 424.3 ± 23.54 versus 398.0 ± 14.93 msec. in men, N.S.). QTc normalized on ketoconazole in one man with prolonged QTc prior to treatment; no abnormal QTc was observed in any other patient during the entire observation period, even during concurrent treatment with other QT-prolonging drugs. In conclusion, long-term ketoconazole administration does not appear to be associated with significant prolongation of QT interval in patients with Cushing's disease. ECG monitoring can follow recommendations drawn for other low-risk QT-prolonging drugs with attention to specific risk factors, for example hypokalaemia and drug interactions.

Improvement of spontaneous language in stroke patients with chronic aphasia treated with music therapy: a randomized controlled trial.

AIM OF THE STUDY: The aim of this research is to evaluate the effects of active music therapy (MT) based on free-improvisation (relational approach) in addition to speech language therapy (SLT) compared with SLT alone (communicative-pragmatic approach: Promoting Aphasic's Communicative Effectiveness) in stroke patients with chronic aphasia. MATERIALS AND METHODS: The experimental group (n = 10) was randomized to 30 MT individual sessions over 15 weeks in addition to 30 SLT individual sessions while the control group (n = 10) was randomized to only 30 SLT sessions during the same period. Psychological and speech language assessment were made before (T0) and after (T1) the treatments. RESULTS: The study shows a significant improvement in spontaneous speech in the experimental group (Aachener Aphasie subtest: p = 0.020; Cohen's d = 0.35); the 50% of the experimental group showed also an improvement in vitality scores of Short Form Health Survey (chi-square test = 4.114; p = 0.043). CONCLUSIONS: The current trial highlights the possibility that the combined use of MT and SLT can lead to a better result in the rehabilitation of patients with aphasia than SLT alone.