A Standards-Based Architecture Proposal for Integrating Patient mHealth Apps to Electronic Health Record Systems.

BACKGROUND: Mobile health Applications (mHealth Apps) are opening the way to patients' responsible and active involvement with their own healthcare management. However, apart from Apps allowing patient's access to their electronic health records (EHRs), mHealth Apps are currently developed as dedicated "island systems". OBJECTIVE: Although much work has been done on patient's access to EHRs, transfer of information from mHealth Apps to EHR systems is still low. This study proposes a standards-based architecture that can be adopted by mHealth Apps to exchange information with EHRs to support better quality of care. METHODS: Following the definition of requirements for the EHR/mHealth App information exchange recently proposed, and after reviewing current standards, we designed the architecture for EHR/mHealth App integration. Then, as a case study, we modeled a system based on the proposed architecture aimed to support home monitoring for congestive heart failure patients. We simulated such process using, on the EHR side, OpenMRS, an open source longitudinal EHR and, on the mHealth App side, the iOS platform. RESULTS: The integration architecture was based on the bi-directional exchange of standard documents (clinical document architecture rel2 - CDA2). In the process, the clinician "prescribes" the home monitoring procedures by creating a CDA2 prescription in the EHR that is sent, encrypted and de-identified, to the mHealth App to create the monitoring calendar. At the scheduled time, the App alerts the patient to start the monitoring. After the measurements are done, the App generates a structured CDA2-compliant monitoring report and sends it to the EHR, thus avoiding local storage. CONCLUSIONS: The proposed architecture, even if validated only in a simulation environment, represents a step forward in the integration of personal mHealth Apps into the larger health-IT ecosystem, allowing the bi-directional data exchange between patients and healthcare professionals, supporting the patient's engagement in self-management and self-care.

A pictorial schema for a comprehensive user-oriented identification of medical Apps.

OBJECTIVES: The huge amount of released medical apps prevents medical app users from believing that medical scientific societies and other accreditation bodies as well, have the resources and the power for assigning to any medical app a quality score. By the time being, any medical app user has to take the risks related to the frequently insufficient accreditation of that app. Providing clear user-oriented schemas, to be adopted both when putting a medical App on the market and when an App comes to be evaluated by a cohort or single users, becomes crucial. The aim of our research was to define a pictorial identification one-shot schema for a comprehensive user-oriented identification of medical apps. METHODS: Adopting a pictorial approach is common in software design modeling. To build up our identification schema we started from the limited number of Apps already available on a web site of app reviews (iMedicalApps.com), and we identified an appropriately large set of attributes for describing medical apps. We arranged the attributes in six main families. We organized them in a one-shot comprehensive pictorial schema. We adopted a traffic light color code for assessing each attribute, that was sufficient to provide simple elements of alerts and alarms regarding a single App. Then, we considered apps from iMedicalApps.com web site belonging to three medical specialties: cardiology, oncology, and pharma and analyzed them according to the proposed pictorial schema. RESULTS: A pictorial schema having the attributes grouped in the families related to "Responsible Promoters", "Offered Services", "Searching Methods", "Applications Domains", "Envisaged Users", and "Qualifiers and Quantifiers" has been identified. Furthermore, we produced a one-shot pictorial schema for each considered app, and for each medical specialty, we produced it also in an aggregated form. CONCLUSIONS: The one-shot pictorial schema provides a useful perception of when and where to use a considered app. It fits positively the expectations of potential but different user's profiles. It can be a first step towards a systematic assessment of apps from the user viewpoint.

A comprehensive e-prescribing model to allow representing, comparing, and analyzing available systems.

BACKGROUND: Even though ePrescribing systems are now available in many healthcare systems and have been a crucial milestone of the roadmaps towards eHealth in the last years, there is still a large heterogeneity among functionalities and performances of different systems. OBJECTIVE: In this paper, we propose an updated comprehensive model for the ePrescribing process able to represent, analyze, and compare current systems and to support the design of new, more general, systems suitable also to sustain the ePrescription process in National Healthcare Systems. METHODS: After a preliminary literature review, we identified six main phases of the ePrescribing process, namely Assign, Transmit, Dispense, Administer, Monitor, and Analysis Decision. Each phase produces a digital object characterized by formal properties that ensure the collection of appropriate data and information and works as input for the next one. The impact, in terms of benefits, of ePrescribing on governance, drug surveillance, and quality of care at the individual, territorial, and governmental levels are related to the formal properties of the digital objects created at the end of each phase. RESULTS AND CONCLUSIONS: The model-based implementation of each phase has an impact on the quality of care, the access to care, and the effectiveness of care delivery. The model does not cover cost evaluation, but the benefits identified can be used as basis for cost-benefit or cost-effectiveness analysis of heterogeneous systems.

Gender-related differences in moral judgments.

The moral sense is among the most complex aspects of the human mind. Despite substantial evidence confirming gender-related neurobiological and behavioral differences, and psychological research suggesting gender specificities in moral development, whether these differences arise from cultural effects or are innate remains unclear. In this study, we investigated the role of gender, education (general education and health education) and religious belief (Catholic and non-Catholic) on moral choices by testing 50 men and 50 women with a moral judgment task. Whereas we found no differences between the two genders in utilitarian responses to non-moral dilemmas and to impersonal moral dilemmas, men gave significantly more utilitarian answers to personal moral (PM) dilemmas (i.e., those courses of action whose endorsement involves highly emotional decisions). Cultural factors such as education and religion had no effect on performance in the moral judgment task. These findings suggest that the cognitive-emotional processes involved in evaluating PM dilemmas differ in men and in women, possibly reflecting differences in the underlying neural mechanisms. Gender-related determinants of moral behavior may partly explain gender differences in real-life involving power management, economic decision-making, leadership and possibly also aggressive and criminal behaviors.

Modulation of beta oscillations in the subthalamic area during action observation in Parkinson's disease.

Mapping observed actions into the onlooker's motor system seems to provide the neurofunctional mechanisms for action understanding. Subthalamic nucleus (STN) local field potential (LFP) recordings in patients with movement disorders disclosed that network oscillations in the beta range are involved in conveying motor and non-motor information across the cortico-basal ganglia-thalamo-cortical loop. This evidence, together with the existence of connections between the STN and cortical areas active during observation of actions performed by other people, suggests that the STN oscillatory activity in specific frequency bands could encode not only motor information, but also information related to action observation. To test this hypothesis we directly recorded STN oscillations through electrodes for deep brain stimulation in patients with Parkinson's disease during observation of actions and of static objects. We found selective action-related oscillatory modulations in two functionally distinct beta bands: whereas low-beta oscillations (10-18 Hz) selectively desynchronized only during action-observation, high-beta oscillations (20-30 Hz) synchronized both during the observation of action and action-related objects. Low-beta modulations are therefore specific to action observation and high-beta modulations are related to the action scene. Our findings show that in the basal ganglia there are functional changes spreading to the action environment, probably presetting the motor system in relation to the motor context and suggesting that the dynamics of beta oscillations can contribute to action understanding mechanisms.

Myoinositol content in the human brain is modified by transcranial direct current stimulation in a matter of minutes: a 1H-MRS study.

Brain content of myoinositol (mI) has been shown to be altered in several neuropsychiatric conditions. Likewise, various forms of electric currents have been applied to the human brain for therapeutic purposes in neuropsychiatric diseases. In this study we aimed to depict the effects of low-power transcranial direct current stimulation (tDCS) on brain mI by proton magnetic resonance spectroscopy ((1)H-MRS). We studied two groups of five healthy subjects by (1)H-MRS: the first group was studied before and after both anodal and sham (placebo) tDCS over the right frontal lobe, and the second group was studied at the same intervals without undergoing either sham or anodal tDCS. Anodal tDCS induced a significant increase of mI content at 30 min after stimulation offset (141.5 +/- 16.7%, P < 0.001) below the stimulating electrode but not in distant regions, such as the visual cortex, whereas sham tDCS failed to induce changes in mI. Neither N-acetyl-aspartate (NAA) nor the other metabolite contents changed after anodal or sham stimulation. (1)H-MRS represents a powerful tool to follow the regional effects of tDCS on brain mI and, possibly, on the related phosphoinositide system.

Subthalamic local field potential oscillations during ongoing deep brain stimulation in Parkinson's disease.

How deep brain stimulation (DBS) acts and how the brain responds to it remains unclear. To investigate the mechanisms involved, we analyzed changes in local field potentials from the subthalamic area (STN-LFPs) recorded through the deep brain macroelectrode during monopolar DBS of the subthalamic nucleus area (STN-DBS) in a group of eight patients (16 nuclei) with idiopathic Parkinson's disease. Monopolar STN-DBS was delivered through contact 1 and differential LFP recordings were acquired between contacts 0 and 2. The stimulating contact was 0.5 mm away from each recording contact. The power spectral analysis of STN-LFPs showed that during ongoing STN-DBS whereas the power of beta oscillations (8-20 Hz) and high beta oscillations (21-40 Hz) remained unchanged, the power of low-frequency oscillations (1-7 Hz) significantly increased (baseline=0.37+/-0.22; during DBS=7.07+/-15.10, p=0.0003). Despite comparable low-frequency baseline power with and without levodopa, the increase in low-frequency oscillations during STN-DBS was over boosted by pretreatment with levodopa. The low-frequency power increase in STN-LFPs during ongoing STN-DBS could reflect changes induced at basal ganglia network level similar to those elicited by levodopa. In addition, the correlation between the heart beat and the low-frequency oscillations suggests that part of the low-frequency power increase during STN-DBS arises from polarization phenomena around the stimulating electrode. Local polarization might in turn also help to normalize STN hyperactivity in Parkinson's disease.

Transcranial direct current stimulation improves recognition memory in Alzheimer disease.

OBJECTIVE: To evaluate the cognitive effect of transcranial direct current stimulation (tDCS) over the temporoparietal areas in patients with Alzheimer disease (AD). METHODS: In 10 patients with probable AD, we delivered anodal tDCS (AtDCS), cathodal tDCS (CtDCS), and sham tDCS (StDCS) over the temporoparietal areas in three sessions. In each session recognition memory and visual attention were tested at baseline (prestimulation) and 30 minutes after tDCS ended (poststimulation). RESULTS: After AtDCS, accuracy of the word recognition memory task increased (prestimulation: 15.5 +/- 0.9, poststimulation: 17.9 +/- 0.8, p = 0.0068) whereas after CtDCS it decreased (15.8 +/- 0.6 vs 13.2 +/- 0.9, p = 0.011) and after StDCS it remained unchanged (16.3 +/- 0.7 vs 16.0 +/- 1.0, p = 0.75). tDCS left the visual attention-reaction times unchanged. CONCLUSION: Transcranial direct current stimulation (tDCS) delivered over the temporoparietal areas can specifically affect a recognition memory performance in patients with Alzheimer disease (AD). Because tDCS is simple, safe and inexpensive, our finding prompts studies using repeated tDCS, in conjunction with other therapeutic interventions for treating patients with AD.

Cerebellar transcranial direct current stimulation impairs the practice-dependent proficiency increase in working memory.

How the cerebellum is involved in the practice and proficiency of non-motor functions is still unclear. We tested whether transcranial direct current stimulation (tDCS) over the cerebellum (cerebellar tDCS) induces after-effects on the practice-dependent increase in the proficiency of a working memory (WM) task (Sternberg test) in 13 healthy subjects. We also assessed the effects of cerebellar tDCS on visual evoked potentials (VEPs) in four subjects and compared the effects of cerebellar tDCS on the Sternberg test with those elicited by tDCS delivered over the prefrontal cortex in five subjects. Our experiments showed that anodal or cathodal tDCS over the cerebellum impaired the practice-dependent improvement in the reaction times in a WM task. Because tDCS delivered over the prefrontal cortex induced an immediate change in the WM task but left the practice-dependent proficiency unchanged, the effects of cerebellar tDCS are structure-specific. Cerebellar tDCS left VEPs unaffected, its effect on the Sternberg task therefore seems unlikely to arise from visual system involvement. In conclusion, tDCS over the cerebellum specifically impairs the practice-dependent proficiency increase in verbal WM.

Improved naming after transcranial direct current stimulation in aphasia.

Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischaemic stroke. This study evaluated the effect of tDCS over the left frontotemporal areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted of the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 minutes) and sham stimulation. Whereas anodal tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly improved the accuracy of the picture naming task by a mean of 33.6% (SEM 13.8%).

Lie-specific involvement of dorsolateral prefrontal cortex in deception.

Lies are intentional distortions of event knowledge. No experimental data are available on manipulating lying processes. To address this issue, we stimulated the dorsolateral prefrontal cortex (DLPFC) using transcranial direct current stimulation (tDCS). Fifteen healthy volunteers were tested before and after tDCS (anodal, cathodal, and sham). Two types of truthful (truthful selected: TS; truthful unselected: TU) and deceptive (lie selected: LS; lie unselected: LU) responses were evaluated using a computer-controlled task. Reaction times (RTs) and accuracy were collected and used as dependent variables. In the baseline task, the RT was significantly longer for lie responses than for true responses ([mean +/- standard error] 1153.4 +/- 42.0 ms vs. 1039.6 +/- 36.6 ms; F(1,14) = 27.25, P = 0.00013). At baseline, RT for selected pictures was significantly shorter than RT for unselected pictures (1051.26 +/- 39.0 ms vs. 1141.76 +/- 41.1 ms; F(1,14) = 34.85, P = 0.00004). Whereas after cathodal and sham stimulation, lie responses remained unchanged (cathodal 5.26 +/- 2.7%; sham 5.66 +/- 3.6%), after anodal tDCS, RTs significantly increased but did so only for LS responses (16.86 +/- 5.0%; P = 0.002). These findings show that manipulation of brain function with DLPFC tDCS specifically influences experimental deception and that distinctive neural mechanisms underlie different types of lies.

Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas.

Neuromuscular fatigue is the exercise-dependent decrease in the ability of muscle fibres to generate force. To investigate whether manipulation of brain excitability by transcranial direct current stimulation (tDCS; 1.5 mA, 10 min, 0.026 C/cm(2)) modulates neuromuscular fatigue, we evaluated the effect of brain polarization over the right motor areas of the cerebral cortex of healthy subjects on the endurance time for a submaximal isometric contraction of left elbow flexors. In 24 healthy volunteers the study protocol comprised an assessment of the maximum voluntary contraction (MVC) for the left elbow flexors and a fatiguing isometric contraction (35% of MVC), before and immediately after brain polarization. One hour elapsed between baseline (T0) and postconditioning (T1) evaluation. After tDCS, MVC remained unchanged from baseline (mean +/- SEM; anodal tDCS: T0, 154.4 +/- 18.07; T1, 142.8 +/- 16.62 N; cathodal tDCS: T0, 156 +/- 18.75; T1, 141.86 +/- 17.53 N; controls: T0, 148.8 +/- 6.64; T1, 137.6 +/- 7.36 N; P > 0.1). Conversely, endurance time decreased significantly less after anodal than after cathodal tDCS or no stimulation (-21.1 +/- 5.5%, -35.7 +/- 3.3% and -39.3 +/- 3.3%, respectively; P < 0.05). None of the evaluated electromyographic variables changed after tDCS. Anodal tDCS could improve endurance time by directly modulating motor cortical excitability, modulating premotor areas, decreasing fatigue-related muscle pain, increasing motivation and improving synergist muscle coupling. Our findings, showing that anodal tDCS over the motor areas of the cerebral cortex improves muscle endurance, open the way to increasing muscle endurance and decreasing muscle fatigue in normal (i.e. sports medicine) and pathological conditions.

An electronic device for artefact suppression in human local field potential recordings during deep brain stimulation.

The clinical efficacy of high-frequency deep brain stimulation (DBS) for Parkinson's disease and other neuropsychiatric disorders likely depends on the modulation of neuronal rhythms in the target nuclei. This modulation could be effectively measured with local field potential (LFP) recordings during DBS. However, a technical drawback that prevents LFPs from being recorded from the DBS target nuclei during stimulation is the stimulus artefact. To solve this problem, we designed and developed 'FilterDBS', an electronic amplification system for artefact-free LFP recordings (in the frequency range 2-40 Hz) during DBS. After defining the estimated system requirements for LFP amplification and DBS artefact suppression, we tested the FilterDBS system by conducting experiments in vitro and in vivo in patients with advanced Parkinson's disease undergoing DBS of the subthalamic nucleus (STN). Under both experimental conditions, in vitro and in vivo, the FilterDBS system completely suppressed the DBS artefact without inducing significant spectral distortion. The FilterDBS device pioneers the development of an adaptive DBS system retroacted by LFPs and can be used in novel closed-loop brain-machine interface applications in patients with neurological disorders.

Gender-related differences in the human subthalamic area: a local field potential study.

The objective of this study was to investigate the possible existence of gender-related neurophysiological differences in the oscillatory activity of the human subthalamic area. To this end, we recorded local field potentials (LFPs) after neurosurgical procedures for deep brain stimulation (DBS) in 24 patients (12 males and 12 females) with Parkinson's disease. LFP recordings at rest before levodopa medication (19 nuclei from 11 female patients and 16 nuclei from ten male patients) showed significantly higher power in the alpha/low-beta band (8-12 Hz, P<0.01; 13-20 Hz, P=0.03) in females than in males. After levodopa medication (ten nuclei from six female patients and 11 nuclei from seven male patients), the power in the high-gamma band (60-90 Hz) and of the 300 Hz rhythm was significantly higher in females than in males (high-gamma, P=0.007; 300 Hz, P=0.002). These findings show that functional gender-related differences in the central nervous system involve the human subthalamic area (STN) and its response to levodopa in Parkinson's disease. Gender-related neurophysiological differences may be important for understanding gender-specific features of neurodegenerative disorders and should be considered when interpreting LFP data from the human basal ganglia.

Low-frequency subthalamic oscillations increase after deep brain stimulation in Parkinson's disease.

This work is the second of a series of papers in which we investigated the neurophysiological basis of deep brain stimulation (DBS) clinical efficacy using post-operative local field potential (LFP) recordings from DBS electrodes implanted in the subthalamic nucleus (STN) in patients with Parkinson's disease. We found that low-frequency (1-1.5Hz) oscillations in LFP recordings from the STN of patients with Parkinson's disease dramatically increase after DBS of the STN itself (log power change=0.93+/-0.62; Wilcoxon: p=0.0002, n=13), slowly decaying to baseline levels after turning DBS off. The DBS-induced increase of low-frequency LFP oscillations is highly reproducible and appears only after the delivery of DBS for a time long enough to induce clinical improvement. This increase of low-frequency LFP oscillations could reflect stimulation-induced modulation of network activity or could represent changes of the electrochemical properties at the brain-electrode interface.

Dopamine-dependent non-linear correlation between subthalamic rhythms in Parkinson's disease.

The basic information architecture in the basal ganglia circuit is under debate. Whereas anatomical studies quantify extensive convergence/divergence patterns in the circuit, suggesting an information sharing scheme, neurophysiological studies report an absence of linear correlation between single neurones in normal animals, suggesting a segregated parallel processing scheme. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and in parkinsonian patients single neurones become linearly correlated, thus leading to a loss of segregation between neurones. Here we propose a possible integrative solution to this debate, by extending the concept of functional segregation from the cellular level to the network level. To this end, we recorded local field potentials (LFPs) from electrodes implanted for deep brain stimulation (DBS) in the subthalamic nucleus (STN) of parkinsonian patients. By applying bispectral analysis, we found that in the absence of dopamine stimulation STN LFP rhythms became non-linearly correlated, thus leading to a loss of segregation between rhythms. Non-linear correlation was particularly consistent between the low-beta rhythm (13-20 Hz) and the high-beta rhythm (20-35 Hz). Levodopa administration significantly decreased these non-linear correlations, therefore increasing segregation between rhythms. These results suggest that the extensive convergence/divergence in the basal ganglia circuit is physiologically necessary to sustain LFP rhythms distributed in large ensembles of neurones, but is not sufficient to induce correlated firing between neurone pairs. Conversely, loss of dopamine generates pathological linear correlation between neurone pairs, alters the patterns within LFP rhythms, and induces non-linear correlation between LFP rhythms operating at different frequencies. The pathophysiology of information processing in the human basal ganglia therefore involves not only activities of individual rhythms, but also interactions between rhythms.