Digital health technologies and major depressive disorder.

There is an urgent need to improve the clinical management of major depressive disorder (MDD), which has become increasingly prevalent over the past two decades. Several gaps and challenges in the awareness, detection, treatment, and monitoring of MDD remain to be addressed. Digital health technologies have demonstrated utility in relation to various health conditions, including MDD. Factors related to the COVID-19 pandemic have accelerated the development of telemedicine, mobile medical apps, and virtual reality apps and have continued to introduce new possibilities across mental health care. Growing access to and acceptance of digital health technologies present opportunities to expand the scope of care and to close gaps in the management of MDD. Digital health technology is rapidly evolving the options for nonclinical support and clinical care for patients with MDD. Iterative efforts to validate and optimize such digital health technologies, including digital therapeutics and digital biomarkers, continue to improve access to and quality of personalized detection, treatment, and monitoring of MDD. The aim of this review is to highlight the existing gaps and challenges in depression management and discuss the current and future landscape of digital health technology as it applies to the challenges faced by patients with MDD and their healthcare providers.

Implementing Digital Technologies in Clinical Trials: Lessons Learned.

Multiple digital health technologies have been evaluated across clinical development programs, including external, wearable, implantable, and ingestible devices and sensors, along with digital mobile health applications (apps) that are accessible via users' personal electronic devices (e.g., smartphones, tablets, and computers). Several of these technologies have been incorporated into our ongoing neurology and respiratory clinical development programs. Based on our experience, one of the greatest potential benefits of digital health technologies is the ability to collect objective and/or biological data continuously or at regular intervals outside of office visits during a patient's normal daily activities to provide additional efficacy and safety information, versus data capture from traditional episodic, time point-based office visits. Many challenges encountered with digital health technologies can be successfully addressed by providing the appropriate training to staff and patients, ensuring availability of appropriate infrastructure support, and conducting pilot studies before scaling up to larger trials. Overall, our experience with digital health technologies demonstrated their potential to increase the amount of objective data collected in clinical trials, expand patient access to trials, and facilitate further improvement of clinical outcomes.

Biometric Digital Health Technology for Measuring Motor Function in Parkinson's Disease: Results from a Feasibility and Patient Satisfaction Study.

OBJECTIVES: To assess the feasibility, predictive value, and user satisfaction of objectively quantifying motor function in Parkinson's disease (PD) through a tablet-based application (iMotor) using self-administered tests. METHODS: PD and healthy controls (HCs) performed finger tapping, hand pronation-supination and reaction time tasks using the iMotor application. RESULTS: Thirty-eight participants (19 with PD and 17 HCs) were recruited in the study. PD subjects were 53% male, with a mean age of 67.8 years (±8.8), mean disease duration of 6.5 years (±4.6), Movement Disorders Society version of the Unified Parkinson Disease Rating Scale III score 26.3 (±6.7), and Hoehn & Yahr stage 2. In the univariate analysis, most tapping variables were significantly different in PD compared to HC. Tap interval provided the highest predictive ability (90%). In the multivariable logistic regression model reaction time (reaction time test) (p = 0.021) and total taps (two-target test) (p = 0.026) were associated with PD. A combined model with two-target (total taps and accuracy) and reaction time produced maximum discriminatory performance between HC and PD. The overall accuracy of the combined model was 0.98 (95% confidence interval: 0.93-1). iMotor use achieved high rates of patients' satisfaction as evaluated by a patient satisfaction survey. CONCLUSION: iMotor differentiated PD subjects from HCs using simple alternating tasks of motor function. Results of this feasibility study should be replicated in larger, longitudinal, appropriately designed, controlled studies. The impact on patient care of at-home iMotor-assisted remote monitoring also deserves further evaluation.

Tablet-Based Application for Objective Measurement of Motor Fluctuations in Parkinson Disease.

BACKGROUND: The motor subscale of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) has limited applicability for the assessment of motor fluctuations in the home setting. METHODS: To assess whether a self-administered, tablet-based application can reliably quantify differences in motor performance using two-target finger tapping and forearm pronation-supination tasks in the ON (maximal dopaminergic medication efficacy) and OFF (reemergence of parkinsonian deficits) medication states, we recruited 11 Parkinson disease (PD) patients (age, 60.6 ± 9.0 years; disease duration, 12.8 ± 4.1 years) and 11 healthy age-matched controls (age, 62.5 ± 10.5 years). The total number of taps, tap interval, tap duration, and tap accuracy were algorithmically calculated by the application, using the more affected side in patients and the dominant hand in healthy controls. RESULTS: Compared to the OFF state, PD patients showed a higher number of taps (84.2 ± 20.3 vs. 54.9 ± 26.9 taps; p = 0.0036) and a shorter tap interval (375.3 ± 97.2 vs. 708.2 ± 412.8 ms; p = 0.0146) but poorer tap accuracy (2,008.4 ± 995.7 vs. 1,111.8 ± 901.3 pixels; p = 0.0055) for the two-target task in the ON state, unaffected by the magnitude of coexistent dyskinesia. Overall, test-retest reliability was high (r >0.75) and the discriminatory ability between OFF and ON states was good (0.60 ≤ AUC ≤ 0.82). The correlations between tapping data and MDS-UPDRS-III scores were only moderate (-0.55 to 0.55). CONCLUSIONS: A self-administered, tablet-based application can reliably distinguish between OFF and ON states in fluctuating PD patients and may be sensitive to additional motor phenomena, such as accuracy, not captured by the MDS-UPDRS-III.

Technology in Parkinson's disease: Challenges and opportunities.

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

Impact of metformin-induced gastrointestinal symptoms on quality of life and adherence in patients with type 2 diabetes.

AIMS: Gastrointestinal (GI) symptoms are common in patients with type 2 diabetes mellitus (T2DM). This study assesses the impact of 1) metformin on GI symptoms and health-related quality of life (HRQoL) and 2) metformin-associated GI symptoms on medication adherence in patients with type 2 diabetes newly beginning therapy. METHODS: Patients with T2DM aged>or=18 years starting metformin from January to June 2007 who filled their prescriptions for >or=3 months were identified from a health benefits company database. Via telephone, GI symptom impact was evaluated in a 360-patient sample using the validated Bowel Symptom Questionnaire and Medical Outcomes Study 36-Item Short-Form Health (SF-36) survey. Adherence was assessed using the medication possession ratio (MPR). Logistic regression adjusting for demographic and clinical covariates was used to assess the relationship between GI symptoms and MPR<80%. RESULTS: The most and least common GI symptoms reported were diarrhea (62.1%) and retching (21.1%), respectively. Most GI symptoms were associated with lower physical and mental HRQoL (P<0.05). Most changes in specific HRQoL reached the minimum important difference of 3 points. Bloating, nausea, and abdominal pain were significantly associated with MPR<80%. Adjustment for demographic, clinical, and HRQoL factors made these relationships less evident. CONCLUSIONS: Metformin-associated GI symptoms in patients with T2DM lead to lower physical and mental HRQoL, which may result in patient nonadherence or physician reluctance to optimally titrate the metformin dose.

Objective tremor registration during DBS surgery for essential tremor.

Essential Tremor (ET) is characterized by a 4-12-Hz postural and kinetic tremor, most commonly affecting the upper limbs. Deep brain stimulation (DBS) of the thalamus (Vim) has been found to be highly effective in severe/refractory forms of ET. Intra-operative assessment of tremor is performed using clinical methods based on patient and physician perception of tremor intensity. We present for the first time the case of a patient whose tremor was objectively monitored/quantified pre- and intra-operatively using device-based tremor registration to supplement clinical measures. We present the case of a 76-year-old right-handed woman that received unilateral (left-sided) DBS of the ventrointermediate (Vim) nucleus of thalamus (Vim) for medically refractory ET. Tremor was monitored with an accelerometer-based Tremor Pen, which is part of a simple portable device (CATSYS 2000 System, Danish Product Development Ltd., DK, www.catsys.dk). The patient was asked to perform tasks for tremor evaluation before and during thalamic DBS. Tremor quantification revealed a significant improvement (34.7-fold) in the contralateral (right) limb following macro-stimulation. No significant improvement was registered in the ipsilateral (non-operated) side. Simple electronic tremor registration methods during DBS of the Vim nucleus of the thalamus may supplement the existing methodology that is solely based on subjective measures derived from clinical observations.

Expression of Lewy body protein septin 4 in postmortem brain of Parkinson's disease and control subjects.

In Parkinson's disease (PD) neuronal degeneration is associated with abnormal protein aggregation in various forms including Lewy bodies (LBs). A major component of LBs is alpha-synuclein; septin 4 (SEPT4), a polymerizing GTP-binding protein that serves as scaffold for diverse molecules has been found to colocalize with alpha-synuclein in LBs. The central role of SEPT4 in the etiopathogenesis of PD has been suggested since SEPT4 also shows a physiological association with alpha-synuclein and serves as a substrate for parkin. To this end, we studied the expression of septin 4 and alpha-synuclein in postmortem human substantia nigra (SN) and amygdala from patients with PD and healthy controls. Twenty patients (14 men : 6 women, onset 63.0 +/- 11.4 years, age 77.3 +/- 7.6 years, Hoehn and Yahr 4.05/5) and 9 neurologically healthy controls (4 men/5 women, age at death 80.1 +/- 8.6 years) were studied. Sporadic PD cases showed a statistically significant decrease of the fold change (FC) of SNCA (FC = 0.31, P = 0.00001) and SEPT4 (FC = 0.67, P = 0.054) gene expressions in the SN and the amygdala (SNCA: FC = 0.49, P = 0.02; SEPT4: FC = 0.32, P = 0.007) versus healthy controls. However, an increase of both proteins in PD versus control subjects was observed with immunoblotting. The semi-quantitative protein ratio calculations revealed more than 10-fold increases for both SEPT4 and alpha-synuclein in PD versus control subjects. We present for the first time similar signal expression patterns and parallel accumulation of SEPT4 and alpha-synuclein in well-characterized postmortem PD brain. Considering the heterogeneous etiology of sporadic PD and the variability of individual human samples, SEPT4 accumulation may be regarded as one of the common pathological changes in PD and should therefore be further explored.

Sarcoidosis with basal ganglial infiltration presenting as Parkinsonism.

The present report describes the case of a woman with symptoms of Parkinsonism (slow and monotonous speech, left foot dragging and micrographia) that gradually developed over a period of 12 months. She had a 10-month history of untreated, asymptomatic sarcoidosis diagnosed by routine biopsy of an enlarged left supraclavicular lymph node. After her condition deteriorated, a brain MRI showed right basal ganglial areas of haemorrhage with perilesional fast fluid-attenuated inversion-recovery (FLAIR) abnormalities. Right stereotactic frame-based brain parenchymal biopsy of the lesion site revealed reactive central nervous system (CNS) tissue with perivascular chronic inflammation and non-caseating granulomas consistent with definite neurosarcoidosis. The patient was started on a high dose of prednisone with good initial response. When mild progression was noted within the next 12 months azathioprine was added to her treatment. The patient's neurological status has been stable without progression of her Parkinsonian symptomatology.

Anterocollis: clinical features and treatment options.

BACKGROUND: Anterocollis (AC) is a form of cervical dystonia (CD) that produces patterned, repetitive muscle contractions that result in neck flexion. It has been mainly described in the context of parkinsonian movement disorders including Parkinson's disease and multiple system atrophy. MATERIAL/METHODS: We performed a review of consecutive AC patients seen in our Movement Disorders Clinic over a 15-year period. The diagnosis of AC was based on degree of abnormal neck anteroflexion. RESULTS: Out of 399 CD patients 27 (6.8%) had features of AC. AC was more prevalent in women (67.3%). It was associated with neuroleptic exposure, PD and a family history of movement/neurological disorder. No definite cases with MSA and AC were described in our cohort. Botulinum toxin injections and tetrabenazine produced clinical improvement. CONCLUSIONS: The demographic and phenotypic features and treatment outcomes of AC in our cohort were somewhat different from other types of CD.

The insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) in Parkinson's disease.

Parkinson's disease (PDI is a neurodegenerative disorder of unknown etiology. Both genetic and environmental factors are thought to be implicated to some extent. The ACE gene insertion/deletion (I/D) polymorphism has been associated with common neurodegenerative disorders that share similar clinical and neuropathological features with PD (Alzheimer's disease). In this study we set out to examine the role of the ACE gene insertion/deletion (I/D) polymorphism in Parkinson's disease (PD).We conducted a case-control association study among 77 PD patients and 50 non-PD controls from Greece. The genotype frequencies for II, ID, and DD were 39, 48, and 13%, respectively, in the PD group and 32, 50, and 18% in the control group. Although the DD frequency was higher in the case group statistical significance was not reached. We conclude that although disease modifying effects cannot be excluded, the ACE insertion/deletion polymorphism is unlikely to be an important determinant of susceptibility to PD in this population.

Patterns of antibiotic use among adults and parents in the community: a questionnaire-based survey in a Greek urban population.

The purpose of this study was to look for factors that affect attitudes to antibiotic use in Greek urban settings. By using a questionnaire-based survey, we conducted 323 face-to-face interviews (173 adults, 150 carers of children). In the adult group, 74.6% admitted using non-prescribed antibiotics, while only 22.7% of parents had administered non-prescribed antibiotics to their children. Around 50% of adults discontinued therapy earlier, more than 10% did not follow the correct dosage instructions and about 55% admitted using leftover antibiotics. Of the parents, 18.7% discontinued therapy earlier and 7.3% admitted keeping leftover antibiotics. Our results showed that adults were likely to show unsatisfactory compliance and to use non-prescribed antibiotics, while parents were less likely to use non-prescribed antibiotics for their children and were more compliant.