Randomised controlled trial of neurostimulation for symptoms of anorexia nervosa (TRENA study): study protocol.

BACKGROUND: Anorexia nervosa (AN) has amongst the highest mortality rates and the highest treatment costs of any psychiatric disorder. Recently, interest in non-invasive brain stimulation as a novel treatment for AN has grown. These include repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). METHODS: This double-blind, randomised sham-controlled trial will compare the relative acceptability and efficacy of tDCS and rTMS in people with AN. 70 participants will be randomised to active or sham tDCS, or active or sham rTMS treatment (2:1:2:1 ratio) over an 8-week treatment period. Participants will receive treatment as usual across the study duration. The primary outcomes are change on the Eating Disorder Examination Questionnaire and treatment acceptability. Secondary outcomes will include change in weight, cognition, mood, interpersonal functioning, and quality of life. Following the 8-week assessment, all participants will have the option of receiving an additional 12 weeks of at-home tDCS. A follow-up assessment will be conducted at 20 weeks post treatment. DISCUSSION: Research into non-invasive brain stimulation as treatments for AN has potential to improve clinical outcomes for patients by comparing the relative efficacy and acceptability of both treatment modalities in the inpatient and at-home setting (i.e., for at-home tDCS) results from this study will provide important information for informing future larger clinical trials of these treatments for AN. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05788042.

Tracking Mechanical Stress and Cell Migration with Inexpensive Polymer Thin-Film Sensors.

Polydiacetylene (PDA) Langmuir films are well known for their blue to red chromatic transitions in response to a variety of stimuli, including UV light, heat, bio-molecule bindings and mechanical stress. In this work, we detail the ability to tune PDA Langmuir films to exhibit discrete chromatic transitions in response to applied mechanical stress. Normal and shear-induced transitions were quantified using the Surface Forces Apparatus and established to be binary and tunable as a function of film formation conditions. Both monomer alkyl tail length and metal cations were used to manipulate the chromatic transition force threshold to enable discrete force sensing from ~50 to ~500 nN µm-2 for normal loading and ~2 to ~40 nN µm-2 for shear-induced transitions, which are appropriate for biological cells. The utility of PDA thin-film sensors was demonstrated with the slime mold Physarum polycephalum. The fluorescence readout of the films enabled: the area explored by Physarum to be visualized, the forces involved in locomotion to be quantified, and revealed novel puncta formation potentially associated with Physarum sampling its environment.

Comparative efficacy, cognitive effects and acceptability of electroconvulsive therapies for the treatment of depression: protocol for a systematic review and network meta-analysis.

INTRODUCTION: There have been important advances in the use of electroconvulsive therapy (ECT) to treat major depressive episodes. These include variations to the type of stimulus the brain regions stimulated, and the stimulus parameters (eg, stimulus duration/pulse width). Our aim is to investigate ECT types using a network meta-analysis (NMA) approach and report on comparative treatment efficacy, cognitive side effects and acceptability. METHOD: We will conduct a systematic review to identify randomised controlled trials that compared two or more ECT protocols to treat depression. This will be done using the following databases: Embase, MEDLINE PubMed, Web of Science, Scopus, PsycINFO, Cochrane CENTRAL and will be supplemented by personal contacts with researchers in the field. All authors will be contacted to provide missing information. Primary outcomes will be symptom severity on a validated continuous clinician-rated scale of depression, cognitive functioning measured using anterograde verbal recall, and acceptability calculated using all-cause drop-outs. Secondary outcomes will include response and remission rates, autobiographical memory following a course of ECT, and anterograde visuospatial recall.Bayesian random effects hierarchical models will compare ECT types. Additional meta-regressions may be conducted to determine the impact of effect modifiers and patient-specific prognostic factors if sufficient data are available. DISCUSSION: This NMA will facilitate clinician decision making and allow more sophisticated selection of ECT type according to the balance of efficacy, cognitive side effects and acceptability. ETHICS: This systematic review and NMA does not require research ethics approval as it will use published aggregate data and will not collect nor disclose individually identifiable participant data. PROSPERO REGISTRATION NUMBER: CRD42022357098.

A Clinical Case Series of Acute and Maintenance Home Administered Transcranial Direct Current Stimulation in Treatment-Resistant Depression.

OBJECTIVES: Transcranial direct current stimulation (tDCS) is a noninvasive neurostimulation technique being translated clinically for the treatment of depression. There is limited research documenting the longer-term effectiveness and safety of tDCS treatment. This case series is the first report of remotely supervised, home-administered tDCS (HA-tDCS) for depression in a clinical setting. METHODS: We report clinical, cognitive, and safety outcomes from 16 depressed patients who received acute and/or maintenance HA-tDCS. We retrospectively examined clinical data from up to 2.5 years of treatment. Descriptive statistics are reported to document patient outcomes. RESULTS: Twelve patients received acute treatment for a current depressive episode and 4 commenced tDCS maintenance therapy after responding to ECT or repetitive transcranial magnetic stimulation (rTMS). The cohort was highly treatment-resistant wherein 15 of 16 patients failed 3 trials or more of antidepressant medication in the current episode, and 6 patients failed to gain significant benefit from prior ECT or rTMS. Five of 12 patients responded to acute tDCS within 6 weeks, and 9 patients who received tDCS for more than 12 weeks maintained improvements over several months. Cognitive tests showed no evidence of impairments in cognitive outcomes after up to 2 years of treatment. Two patients were withdrawn from treatment because of blurred vision or exacerbation of tinnitus. Transcranial direct current stimulation was otherwise safe and well tolerated. CONCLUSIONS: Transcranial direct current stimulation given for at least 6 weeks may be of clinical benefit even in treatment-resistant depression. Results provide support for long-term effectiveness, safety, and feasibility of remotely supervised HA-tDCS and suggest a role for maintenance tDCS after acute treatment with tDCS, rTMS, or ECT.

Feasibility, Reliability, and Value of Remote Video-Based Trial Visits in Parkinson's Disease.

BACKGROUND: There is rising interest in remote clinical trial assessments, particularly in the setting of the COVID-19 pandemic. OBJECTIVE: To demonstrate the feasibility, reliability, and value of remote visits in a phase III clinical trial of individuals with Parkinson's disease. METHODS: We invited individuals with Parkinson's disease enrolled in a phase III clinical trial (STEADY-PD III) to enroll in a sub-study of remote video-based visits. Participants completed three remote visits over one year within four weeks of an in-person visit and completed assessments performed during the remote visit. We evaluated the ability to complete scheduled assessments remotely; agreement between remote and in-person outcome measures; and opinions of remote visits. RESULTS: We enrolled 40 participants (mean (SD) age 64.3 (10.4), 29% women), and 38 (95%) completed all remote visits. There was excellent correlation (ICC 0.81-0.87) between remote and in-person patient-reported outcomes, and moderate correlation (ICC 0.43-0.51) between remote and in-person motor assessments. On average, remote visits took around one quarter of the time of in-person visits (54 vs 190 minutes). Nearly all participants liked remote visits, and three-quarters said they would be more likely to participate in future trials if some visits could be conducted remotely. CONCLUSION: Remote visits are feasible and reliable in a phase III clinical trial of individuals with early, untreated Parkinson's disease. These visits are shorter, reduce participant burden, and enable safe conduct of research visits, which is especially important in the COVID-19 pandemic.

The anaesthetic-ECT time interval with thiopentone-Impact on seizure quality.

BACKGROUND: The time between anaesthetic induction and ECT stimulus administration has been hypothesised to significantly impact ictal EEG quality. In this study, our aim was to examine the effect of the time interval between anaesthetic induction and the ECT stimulus for ictal seizure quality in ECT sessions utilising thiopentone anaesthesia. METHODS: 413 EEG traces from 42 patients, collected retrospectively, were manually rated using a quantitative-qualitative structured rating scale (indices including seizure amplitude, regularity, post-ictal suppression and general seizure quality). Linear Mixed Effects Models were used to analyse the effect of the anaesthetic-ECT time interval on seizure quality indices, seizure duration and orientation scores after ECT, controlling for patient and ECT treatment factors. RESULTS: The anaesthetic-ECT time interval had a significant impact on ictal EEG quality indices (p < 0.05), with longer times producing higher quality seizures. Seizure duration and orientation scores after ECT were not significantly influenced by the anaesthetic-ECT time interval. Age, anaesthetic dose, ECT type and ECT treatment number also had a significant impact on measures of seizure quality (p < 0.05). LIMITATIONS: The effect of ventilation technique was not explicitly measured. Only manual ratings of ictal quality were analysed. CONCLUSIONS: The time between anaesthetic induction and ECT stimulus administration has a significant impact on the ictal EEG seizure quality observed, with thiopentone anaesthetic. These results are consistent with prior findings with propofol anaesthesia, and suggest a need for routine clinical monitoring of this time interval. This variable warrants consideration when interpreting ictal EEGs, which often informs subsequent dosing decisions.

Calibration and validation of Airborne Multiangle SpectroPolarimetric Imager (AirMSPI) polarization measurements.

The Airborne Multiangle SpectroPolarimetric Imager (AirMSPI), a precursor to the future Multi-Angle Imager for Aerosols satellite instrument, is a remote-sensing instrument for the characterization of atmospheric aerosols and clouds. To help discriminate between different aerosol particle types, which is crucial to improve our understanding of their impact on climate and air quality, AirMSPI acquires imagery over multiple view angles in the ultraviolet, visible, and near-infrared, and it employs dual photoelastic modulators (PEMs) to target an uncertainty requirement of ±0.005 in the degree of linear polarization (DoLP) at selected wavelengths. Laboratory polarimetric calibrations using a second-generation Polarization State Generator-2 (PSG-2) and validation measurements at 0

National Randomized Controlled Trial of Virtual House Calls for People with Parkinson's Disease: Interest and Barriers.

BACKGROUND: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. MATERIALS AND METHODS: Connect.Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based videoconferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. RESULTS: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. CONCLUSIONS: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.

A feasibility study of conducting the Montreal Cognitive Assessment remotely in individuals with movement disorders.

Remote assessments of individuals with a neurological disease via telemedicine have the potential to reduce some of the burdens associated with clinical care and research participation. We aim to evaluate the feasibility of conducting the Montreal Cognitive Assessment remotely in individuals with movement disorders. A pilot study derived from two telemedicine trials was conducted. In total, 17 individuals with movement disorders (8 with Parkinson disease and 9 with Huntington disease) had Montreal Cognitive Assessment examinations evaluated in-person and remotely via web-based video conferencing to primarily determine feasibility and potential barriers in its remote administration. Administering the Montreal Cognitive Assessment remotely in a sample of movement disorder patients with mild cognitive impairment is feasible, with only minor common complications associated with technology, including delayed sound and corrupted imaging for participants with low connection speeds. The Montreal Cognitive Assessment has the potential to be used in remote assessments of patients and research participants with movement disorders.

Feasibility of Virtual Research Visits in Fox Trial Finder.

BACKGROUND: Fox Trial Finder is an online registry for individuals with and without Parkinson disease (PD) interested in participating in PD research. However, distance or disability could prevent such individuals from participating in traditional, clinic-based research at major centers. OBJECTIVE: Use videoconferencing to connect participants to specialists to: (1) demonstrate feasibility of virtual research visits within this population (2) collect phenotypic data of the participants, (3) validate self-reported diagnosis, and (4) gauge interest in virtual research visits. METHODS: We solicited volunteers throughout the United States through Fox Trial Finder. Interested individuals with PD provided consent, were given web cameras if needed, completed baseline surveys, and downloaded videoconferencing software remotely. Participants had a test connection and assessment appointment which included the Montreal Cognitive Assessment (MoCA), then a virtual research visit with a neurologist who reviewed their history and assessed their PD using a modified Movement Disorders Society Unified Parkinson's Disease Rating Scale. Neurologists assessed PD diagnosis and symptomatology. Physicians and participants were surveyed about their experience. RESULTS: Of 204 individuals who consented, 166 (81% ) individuals from 39 states completed all visits. The mean age was 62 and mean disease duration was 8.0 years. Mean MoCA score was 26.5, and mean modified MDS-UPDRS motor score was 22.8 (out of a possible 124). Neurologists judged PD as the most likely diagnosis in 97% of cases. Overall satisfaction with the visits was 79% (satisfied or very satisfied) among neurologists and 93% among participants. CONCLUSIONS: Through virtual research visits, neurologists engaged, characterized, and validated self-reported diagnosis in individuals with PD over a broad geography. This model may facilitate future research participation.

A pilot study of virtual visits in Huntington disease.

BACKGROUND: Virtual visits through web-based video conferencing can increase access to specialty care for individuals with Huntington disease (HD) and facilitate research participation. OBJECTIVE: To determine the feasibility of conducting virtual visits directly into the homes of individuals with HD, to assess the reliability of conducting remote versus in-person motor assessments, and to determine the test-retest reliability of conducting motor assessments remotely. METHODS: Individuals with mild to moderate HD underwent baseline in-person clinic assessments and completed a HD care survey. Participants were randomized to receive three virtual visits from one of two physicians over four months that included a modified Unified Huntington's Disease Rating Scale motor examination (excluding rigidity and balance assessments) via web-based video conferencing. Intraclass coefficients (ICC) were calculated to determine the level of agreement between remote and in-person assessments. Participants also completed a survey on their interest in telemedicine. RESULTS: Thirteen individuals underwent baseline assessments, eleven (85%) participants completed at least one virtual visit, and 27 (82%) of 33 total virtual visits were completed. Remote motor scores demonstrated good reliability (ICC = 0.78; n = 11) compared to in-person motor scores. Test-retest reliability of motor scores conducted remotely was excellent (ICC = 0.90; n = 11). Participants expressed moderate future interest in using virtual visits to participate in research and to receive care. CONCLUSION: In this pilot study, virtual visits into the home were feasible and reliable for conducting motor assessments in HD. Larger scale studies need to confirm and generalize these findings to a broader population of participants.

Randomized controlled clinical trial of "virtual house calls" for Parkinson disease.

IMPORTANCE: The burden of neurological disorders is increasing, but access to care is limited. Providing specialty care to patients via telemedicine could help alleviate this growing problem. OBJECTIVE: To evaluate the feasibility, effectiveness, and economic benefits of using web-based videoconferencing (telemedicine) to provide specialty care to patients with Parkinson disease in their homes. DESIGN: A 7-month, 2-center, randomized controlled clinical trial. SETTING: Patients' homes and outpatient clinics at 2 academic medical centers. PARTICIPANTS: Twenty patients with Parkinson disease with Internet access at home. INTERVENTION: Care from a specialist delivered remotely at home or in person in the clinic. MAIN OUTCOME MEASURES: The primary outcome variable was feasibility, as measured by the percentage of telemedicine visits completed as scheduled. Secondary outcome measures included clinical benefit, as measured by the 39-item Parkinson Disease Questionnaire, and economic value, as measured by time and travel. RESULTS: Twenty participants enrolled in the study and were randomly assigned to telemedicine (n = 9) or in-person care (n = 11). Of the 27 scheduled telemedicine visits, 25 (93%) were completed, and of the 33 scheduled in-person visits, 30 (91%) were completed (P = .99). In this small study, the change in quality of life did not differ for those randomly assigned to telemedicine compared with those randomly assigned to in-person care (4.0-point improvement vs 6.4-point improvement; P = .61). Compared with in-person visits, each telemedicine visit saved participants, on average, 100 miles of travel and 3 hours of time. CONCLUSION AND RELEVANCE: Using web-based videoconferencing to provide specialty care at home is feasible, provides value to patients, and may offer similar clinical benefit to that of in-person care. Larger studies are needed to determine whether the clinical benefits are indeed comparable to those of in-person care and whether the results observed are generalizable. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01476306.

Neurotransmitters excreted in the urine as biomarkers of nervous system activity: validity and clinical applicability.

Strategies for managing the nervous system are numerous while methods of evaluating the nervous system are limited. Given the physiological importance of neurotransmitters as signaling molecules in the nervous system, the measurement of neurotransmitters has significant potential as a clinical tool. Of all the biological fluids that can be utilized, urinary neurotransmitter testing, due to its stability, sensitivity, and non-invasiveness, is the desired method to analyze nervous system function. Increasing use of this technology in a clinical setting demands a review of its feasibility, utility, and clinical value. We review the current body of literature pertaining to the mechanism of neurotransmitter transport across the blood-brain barrier as well as neurotransmitter filtration and excretion by the kidneys. In addition, this review summarizes the historical use of urinary neurotransmitter assessment to diagnose pheochromocytoma. Early research also correlated urinary assessment of neurotransmitters to various clinical symptoms and treatments of which we present research only for depression, ADHD, and inflammation because of the abundant amount of research in these areas. Finally, we review the limitations and challenges of urinary neurotransmitter testing. Taken together, evidence suggests that neurotransmitters excreted in the urine may have a place in clinical practice as a biomarker of nervous system function to effectively assess disturbances and monitor treatment efficacy.

First results from a dual photoelastic-modulator-based polarimetric camera.

We report on the construction and calibration of a dual photoelastic-modulator (PEM)-based polarimetric camera operating at 660?nm. This camera is our first prototype for a multispectral system being developed for airborne and spaceborne remote sensing of atmospheric aerosols. The camera includes a dual-PEM assembly integrated into a three-element, low-polarization reflective telescope and provides both intensity and polarization imaging. A miniaturized focal-plane assembly consisting of spectral filters and patterned wire-grid polarizers provides wavelength and polarimetric selection. A custom push-broom detector array with specialized signal acquisition, readout, and processing electronics captures the radiometric and polarimetric information. Focal-plane polarizers at orientations of 0 degrees and -45 degrees yield the normalized Stokes parameters q=Q/I and u=U/I respectively, which are then coregistered to obtain degree of linear polarization (DOLP) and angle of linear polarization. Laboratory test data, calibration results, and outdoor imagery acquired with the camera are presented. The results show that, over a wide range of DOLP, our challenging objective of uncertainty within +/-0.005 has been achieved.

Developing and evaluating the GriefLink web site: processes, protocols, dilemmas and lessons learned.

Despite a profusion of recommendations regarding the quality of web sites and guidelines related to ethical issues surrounding health-related sites, there is little guidance for the design and evaluation of sites relating to loss and grief. This article, which addresses these deficiencies, results from a community consultation process of designing and evaluating a web site--GriefLink--for bereaved consumers and for the professionals who help them. It presents the literature review that informed the project, the recommendations for design and content, the lessons learned through the process itself, and the difficulties of evaluating the benefits of a grief-related web site. Some ethical and legal dilemmas in developing grief-related web sites are discussed and issues of design, content, process, evaluation, and general features are addressed, which may also be applied to other communication forms for loss and grief matters, such as the print media.