Feasibility of regional center telehealth visits utilizing a rural research network in people with Parkinson's disease.

Background: Impaired motor and cognitive function can make travel cumbersome for People with Parkinson's disease (PwPD). Over 50% of PwPD cared for at the University of Arkansas for Medical Sciences (UAMS) Movement Disorders Clinic reside over 30 miles from Little Rock. Improving access to clinical care for PwPD is needed. Objective: To explore the feasibility of remote clinic-to-clinic telehealth research visits for evaluation of multi-modal function in PwPD. Methods: PwPD residing within 30 miles of a UAMS Regional health center were enrolled and clinic-to-clinic telehealth visits were performed. Motor and non-motor disease assessments were administered and quantified. Results were compared to participants who performed at-home telehealth visits using the same protocols during the height of the COVID pandemic. Results: Compared to the at-home telehealth visit group (n = 50), the participants from regional centers (n = 13) had similar age and disease duration, but greater disease severity with higher total Unified Parkinson's disease rating scale scores (Z = -2.218, p = 0.027) and lower Montreal Cognitive Assessment scores (Z = -3.350, p < 0.001). Regional center participants had lower incomes (Pearson's chi = 21.3, p < 0.001), higher costs to attend visits (Pearson's chi = 16.1, p = 0.003), and lived in more socioeconomically disadvantaged neighborhoods (Z = -3.120, p = 0.002). Prior research participation was lower in the regional center group (Pearson's chi = 4.5, p = 0.034) but both groups indicated interest in future research participation. Conclusions: Regional center research visits in PwPD in medically underserved areas are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

Etiology and incidence of postpartum depression among birthing women in the scenario of pandemics, geopolitical conflicts and natural disasters: a systematic review.

Postpartum depression (PPD) is classified under postpartum psychiatric disorders and initiates soon after birthing, eliciting neuropsychological and behavioral deficits in mothers and offspring. Globally, PPD is estimated to be associated with 130-190 per 1000 birthing. The severity and incidences of PPD have aggravated in the recent years due to the several unfavorable environmental and geopolitical circumstances. The purpose of this systematic review hence is to explore the contributions of recent circumstances on the pathogenesis and incidence of PPD. The search, selection and retrieval of the articles published during the last three years were systematically performed. The results from the primary studies indicate that unfavorable contemporary socio-geopolitical and environmental circumstances (e.g. Covid-19 pandemic, political conflicts/wars, and natural calamities; such as floods and earthquakes) detrimentally affect PPD etiology. A combination of socio-economic and psychological factors, including perceived lack of support and anxiousness about the future may contribute to drastic aggravation of PPD incidences. Finally, we outline some of the potential treatment regimens (e.g. inter-personal psycho- and art-based therapies) that may prove to be effective in amelioration of PPD-linked symptoms in birthing women, either alone or in complementation with traditional pharmacological interventions. We propose these psychological and art-based intervention strategies may beneficially counteract the negative influences of the unfortunate recent events across multiple cultures, societies and geographical regions.

Development and implementation of the frog-in-maze game to study upper limb movement in people with Parkinson's disease.

Upper-limb bradykinesia occurs early in Parkinson's disease (PD) and bradykinesia is required for diagnosis. Our goal was to develop, implement and validate a game "walking" a frog through a maze using bimanual, alternating finger-tapping movements to provide a salient, objective, and remotely monitorable method of tracking disease progression and response to therapy in PD. Twenty-five people with PD and 16 people without PD participated. Responses on 5 different mazes were quantified and compared to spatiotemporal gait parameters and standard disease metrics in these participants. Intertap interval (ITI) on maze 2 & 3, which included turns, was strongly inversely related to stride-length and stride-velocity and directly related to motor UPDRS scores. Levodopa decreased ITI, except in maze 4. PD participants with freezing of gait had longer ITI on all mazes. The responses quantified on maze 2 & 3 were related to disease severity and gait stride-length, were levodopa responsive, and were worse in people with freezing of gait, suggesting that these mazes could be used to quantify motor dysfunction in PD. Programming our frog-in-maze game onto a remotely distributable platform could provide a tool to monitor disease progression and therapeutic response in people with PD, including during clinical trials.

A machine learning method to process voice samples for identification of Parkinson's disease.

Machine learning approaches have been used for the automatic detection of Parkinson's disease with voice recordings being the most used data type due to the simple and non-invasive nature of acquiring such data. Although voice recordings captured via telephone or mobile devices allow much easier and wider access for data collection, current conflicting performance results limit their clinical applicability. This study has two novel contributions. First, we show the reliability of personal telephone-collected voice recordings of the sustained vowel /a/ in natural settings by collecting samples from 50 people with specialist-diagnosed Parkinson's disease and 50 healthy controls and applying machine learning classification with voice features related to phonation. Second, we utilize a novel application of a pre-trained convolutional neural network (Inception V3) with transfer learning to analyze the spectrograms of the sustained vowel from these samples. This approach considers speech intensity estimates across time and frequency scales rather than collapsing measurements across time. We show the superiority of our deep learning model for the task of classifying people with Parkinson's disease as distinct from healthy controls.

Profile of cardiac lesions among laboratory confirmed congenital rubella syndrome (CRS) infants: a nationwide sentinel surveillance, India, 2016-22.

Background: The phenotypical profile of cardiovascular malformations in patients with congenital rubella syndrome (CRS) is varied. We aimed to describe the profile of cardiac defects among CRS patients detected in the sentinel CRS surveillance in India during 2016-22. Methods: Sentinel sites enrolled infants with suspected CRS based on presence of cardiac defects, hearing impairment, eye signs, or maternal history of febrile rash illness. Suspected CRS cases underwent detailed systemic examination, including echocardiography and serological investigation for rubella. Cardiac defects were categorized as 'Simple' or 'Complex' as per the National Heart, Lung, and Blood Institute classification. We compared the distribution of cardiac defects among laboratory confirmed CRS cases and seronegative discarded cases. Findings: Of the 4578 suspected CRS cases enrolled by 14 sites, 558 (12.2%) were laboratory confirmed. 419 (75.1%) laboratory confirmed cases had structural heart defects (simple defects: n = 273, 65.2%, complex defects: n = 144, 34.4%), with ventricular septal defect (42.7%), atrial septal defect (39.4%), patent ductus arteriosus (36.5%), and tetralogy of Fallot as the commonest defects (4.5%). Laboratory confirmed CRS cases had higher odds of left to right shunt lesions (OR = 1.58, 95% CI: 1.15-2.17). This was mainly on account of a significant association of PDA with CRS (OR = 1.77, 95% CI: 1.42-2.21). Mortality was higher among CRS patients with complex heart defects (HR = 2.04, 95% CI: 1.26-3.30). Interpretation: Three-fourths of the laboratory confirmed CRS cases had structural heart defects. CRS patients with complex cardiac defects had higher mortality. Detecting CRS infection early and providing timely intervention for cardiovascular defects is critical for the management of CRS patients. Funding: Ministry of Health and Family Welfare, Govt of India, through Gavi, the Vaccine Alliance.

Gait Declines Differentially in, and Improves Prediction of, People with Parkinson's Disease Converting to a Freezing of Gait Phenotype.

BACKGROUND: Freezing of gait (FOG) is a debilitating, variably expressed motor symptom in people with Parkinson's disease (PwPD) with limited treatments. OBJECTIVE: To determine if the rate of progression in spatiotemporal gait parameters in people converting from a noFOG to a FOG phenotype (FOGConv) was faster than non-convertors, and determine if gait parameters can help predict this conversion. METHODS: PwPD were objectively monitored longitudinally, approximately every 6 months. Non-motor assessments were performed at the initial visit. Steady-state gait in the levodopa ON-state was collected using a gait mat (Protokinetics) at each visit. The rate of progression in 8 spatiotemporal gait parameters was calculated. FOG convertors (FOGConv) were classified if they did not have FOG at initial visit and developed FOG at a subsequent visit. RESULTS: Thirty freezers (FOG) and 30 non-freezers were monitored an average of 3.5 years, with 10 non-freezers developing FOG (FOGConv). FOGConv and FOG had faster decline in mean stride-length, swing-phase-percent, and increase in mean total-double-support percent, coefficient of variability (CV) foot-strike-length and CV swing-phase-percent than the remaining non-freezers (noFOG). On univariate modeling, progression rates of mean stride-length, stride-velocity, swing-phase-percent, total-double-support-percent and of CV swing-phase-percent had high discriminative power (AUC > 0.83) for classification of the FOGConv and noFOG groups. CONCLUSION: FOGConv had a faster temporal decline in objectively quantified gait than noFOG, and progression rates of spatiotemporal gait parameters were more predictive of FOG phenotype conversion than initial (static) parameters Objectively monitoring gait in disease prediction models may help define FOG prone groups for testing putative treatments.

Levodopa responsive gait dynamics in OFF- and ONOFF-state freezing of gait in Parkinson's disease.

Background: In people with Parkinson's disease (PwPD), Freezing of Gait (FOG) episodes can be levodopa responsive (OFF-FOG) or levodopa unresponsive (ONOFF-FOG). Steady-state gait abnormalities, outside of the freezing episodes themselves also exist and the response to levodopa in these different groups has not been previously documented. Objectives: To define the levodopa responsiveness in steady-state gait in OFF-FOG and ONOFF-FOG individuals. Methods: Steady-state gait was collected in both the effective levodopa OFF-state (doses withheld > 8 h) and ON-state (1 h after levodopa dosing) in 32 PwPD; 10 with OFF-FOG and 22 with ONOFF-FOG. Levodopa response was compared between the two groups in the mean and variability (CV) of 8 spatiotemporal gait parameters. Results: Both OFF-FOG and ONOFF-FOG participants showed improvement in mean stride-length and stride-velocity with levodopa. Improvement was seen in the OFF-FOG but not the ONOFF-FOG groups in mean stride-width and CV Integrated pressure with levodopa. Discussion: In this study we show that steady-state gait deficits improve with levodopa in PwPD with OFF-FOG and ONOFF-FOG, even though episodes of FOG did not resolve in the ONOFF-FOG group. Lowering levodopa in people with ONOFF-FOG, or levodopa-unresponsive freezing of gait, should be undertake with caution and objective gait titration at different levodopa doses may be beneficial. Further work is needed to elucidate the pathophysiologic mechanisms of these differences.

Objective quantification of responses to the clinical pull-test in people with Parkinson's disease.

BACKGROUND: Postural instability can occur in the later-stages of Parkinson's disease (PD). The clinical pull-test is scored on a 0-4 scale on the Unified Parkinson's disease rating scale (UPDRS), with postural instability scored 2 or higher. This ordinal scale does not adequately track progression in early-PD or predict development of postural instability. RESEARCH QUESTION: To develop a test that quantifiably measured the backward stepping response on the pull-test in early-PD. METHODS: Participants (35 controls and 79 PD participants) were prospectively enrolled in this study. Participants stepped backwards with each shoulder pull at four strengths on an instrumented gait mat. Four spatiotemporal parameters (reaction-time, step-back-time, step-back-distance, step-back-velocity) were quantified using Protokinetics Movement Analysis Software. Spatiotemporal pull-test parameters were compared to standard PD measures using linear regression and correlation coefficients. Repeated measures analysis was used to determine group differences in pull-test parameters. In a subset of participants repeated testing was performed and Bland-Altman plots were used to determine reproducibility of the pull-test parameters. RESULT: Step-back-distance and step-back-velocity were inversely related to motor UPDRS and freezing of gait questionnaire scores. PD participants had shorter step-back-distance than controls adjusted for age and sex. Repeat assessments in 16 participants, on average 0.7 years apart, showed good agreement on most of the quantified parameters. SIGNIFICANCE: The backward stepping response in PD participants was quantifiable, reproducible, and related to disease severity and could be used to quantify progression towards postural instability in early-PD.

Real world reduction in red cell transfusion with restrictive transfusion threshold in haematology inpatients.

OBJECTIVES: The aim of this study was to assess the reduction in red cell transfusions following a change in the red cell transfusion threshold for haematology inpatients from 80 to 70 g/L. BACKGROUND: Haematology patients are among the high users of red blood cells. We reduced the threshold for transfusion of haematology inpatients to 70 g/L. This was based on evidence provided by randomised controlled trial published in 2020 that showed restrictive transfusion is non-inferior to liberal transfusion. METHOD: We assessed red cell transfusions for haematology inpatients at Oxford University Hospitals NHS Foundation Trust for 9 months before and 9 months after a change in red cell transfusion threshold from 80 to 70 g/L. RESULTS: After the change in threshold to 70 g/L or less from 80 g/L, the median number of red cell transfusions per month reduced to 88 from 111. This was a 23% reduction in the total number of red cells administered per month. CONCLUSION: These results show the real-world reductions in transfusion that can be made by putting local transfusion guidelines in line with the international recommendations. This is of particular importance at a time of national blood shortage.

Levodopa ONOFF-state freezing of gait: Defining the gait and non-motor phenotype.

BACKGROUND: Freezing in the levodopa-medicated-state (ON-state) is a debilitating feature of Parkinson's disease without treatment options. Studies detailing the distinguishing features between people with freezing of gait that improves with levodopa and those whose freezing continues even on levodopa are lacking. OBJECTIVE: To characterize the gross motor, gait, and non-motor features of this phenotype. METHODS: Instrumented continuous gait was collected in the levodopa-medicated-state in 105 patients: 43 non-freezers (no-FOG), 36 with freezing only OFF-levodopa (OFF-FOG) and 26 with freezing both ON- and OFF-levodopa (ONOFF-FOG). Evaluation of motor and non-motor disease features was undertaken using validated scales. A linear mixed model with age, sex, disease duration, and motor UPDRS scores as covariates was used to determine differences in spatiotemporal gait and non-motor disease features among the groups. RESULTS: Compared to OFF-FOG, the ONOFF-FOG group had greater disease severity (on the Unified Parkinson's disease Rating Scale) and worse cognition (on the Montreal Cognitive Assessment, Frontal Assessment Battery and Scales for Outcome in Parkinson's disease-Cognition scales) and quality of life (on the PDQ-39), but similar mood (on the Hamilton depression and anxiety scales) and sleep quality (on Epworth sleepiness scale and RBD questionnaire). For several gait features, differences between the ONOFF-OFF groups were at least as large and in the opposite direction as differences between OFF-no groups, controlling for disease severity. Variability in ONOFF-FOG was greater than in other groups. Using results from our study and others, a power analysis for a potential future study reveals sample sizes of at least 80 ONOFF and 80 OFF-FOG patients would be needed to detect clinically meaningful differences. CONCLUSIONS: Intra-patient variability in spatiotemporal gait features was much greater in ONOFF-FOG than in the other two groups. Our results suggest that multifactorial deficits may lead to ONOFF-FOG development.

A study of turn bias in people with idiopathic Parkinson's disease.

The objective of the study is to explore whether people with Parkinson's disease (PwPD) display a preferential turn bias dependent upon disease asymmetry, and whether specific disease features predict turn bias. PwPD and age-matched controls were instructed to walk on an instrumented gait mat making "normal" turns. Trials were analyzed using Proto Kinetics Movement Analysis Software (PKMAS) and time-locked video recordings to obtain turn directionality and spatiotemporal turn measures. Turn bias was estimated using previously defined formulas. Seventy-two PwPD and 28 controls were included. One hundred percent of controls and 85% of PwPD had left turn bias. Turn bias was not significantly associated with age, gender, handedness, disease asymmetry, cognition, or disease severity. The Freezing of Gait Questionnaire (FOGQ) questions 5 and 6 showed linear-by-linear association with turn bias. In binary logistic and ordinal regression models, FOGQ question 6 (average duration of turn freezing) and turn width were predictive of turn bias. Rightward turns had greater frequency of freezing episodes. Turn bias in our PwPD cohort does not appear related to disease asymmetry or other disease features, except gait freezing. Whether freezing severity on turning leads to non-left turn bias or vice versa requires more focused studies. Physical therapy interventions targeting turning direction in PwPD could reduce freezing severity.

Amplitude setting and dopamine response of finger tapping and gait are related in Parkinson's disease.

Movement amplitude setting is affected early in Parkinson's disease (PD), clinically manifesting as bradykinesia. Our objective was to determine if amplitude setting of upper limb bimanual movements and bipedal gait are similarly modulated in PD. 27 PD and 24 control participants were enrolled. Participants performed a bimanual anti-phase finger tapping task wearing gloves with joint angular sensors, and an instrumented gait assessment. Participants performed normal and fast paced assessments to vary motor load. PD participants were evaluated OFF (PD-OFF) and ON (PD-ON) levodopa. PD-OFF participants had smaller tap amplitude, and greater tap amplitude variability than controls in the more affected hands (all p < 0.05). Tap amplitude and stride length (p = 0.030) were correlated in PD-OFF. Tap amplitude was also correlated with motor UPDRS (p < 0.005) and bradykinesia motor (p < 0.05) and ADL (p < 0.005) UPDRS subscores. The relative amount of improvement in tap amplitude and stride length with levodopa was correlated. In PD, upper limb and gait amplitude setting are similarly scaled with motor demand and dopamine supplementation. This suggests these automated motor functions are subserved by common functional networks.

Feasibility of telemedicine research visits in people with Parkinson's disease residing in medically underserved areas.

Introduction: Gait, balance, and cognitive impairment make travel cumbersome for People with Parkinson's disease (PwPD). About 75% of PwPD cared for at the University of Arkansas for Medical Sciences' Movement Disorders Clinic reside in medically underserved areas (MUAs). Validated remote evaluations could help improve their access to care. Our goal was to explore the feasibility of telemedicine research visits for the evaluation of multi-modal function in PwPD in a rural state. Methods: In-home telemedicine research visits were performed in PwPD. Motor and non-motor disease features were evaluated and quantified by trained personnel, digital survey instruments for self-assessments, digital voice recordings, and scanned and digitized Archimedes spiral drawings. Participant's MUA residence was determined after evaluations were completed. Results: Twenty of the fifty PwPD enrolled resided in MUAs. The groups were well matched for disease duration, modified motor UPDRS, and Montreal Cognitive assessment scores but MUA participants were younger. Ninety-two percent were satisfied with their visit, and 61% were more likely to participate in future telemedicine research. MUA participants traveled longer distances, with higher travel costs, lower income, and education level. While 50% of MUA participants reported self-reliance for in-person visits, 85% reported self-reliance for the telemedicine visit. We rated audio-video quality highly in approximately 60% of visits in both groups. There was good correlation with prior in-person research assessments in a subset of participants. Conclusions: In-home research visits for PwPD in MUAs are feasible and could help improve access to care and research participation in these traditionally underrepresented populations.

Increased foot strike variability during turning in Parkinson's disease patients with freezing of gait.

BACKGROUND: Turning is a common trigger for freezing episodes in patients with Parkinson's disease (PD). Freezing during turning can lead to falls and fractures and decreased quality of life. RESEARCH QUESTION: Does foot-strike contact variability also increase during turning, as previously reported in straight gait in PD patients with Freezing of Gait (FOG)? METHODS: Subjects were instructed to walk on a gait mat, making "normal pivot" (180°) turns at each end. ProtoKinetics Movement Analysis Software (PKMAS) software was used for analysis. Video recordings and foot-pressure-prints were studied to identify and define turn segments. Spatiotemporal gait and turn measures were then determined only for the turn segments. A movement disorders neurologist determined clinical freezes. RESULTS: 100 subjects (28 controls, 38 noFOG and 34 FOG) were included. Compared to non-freezers (noFOG), FOG subjects had a smaller foot-strike during turning (a measure of completeness of foot contact with the mat) and increased foot-strike variability. FOG subjects also had a shorter stride-length, slower stride-velocity, and greater swing phase time and percentage during turns. After adjusting for turn direction, inner/outer leg dynamics showed heavier inner leg footsteps in FOG subjects. 38% of FOG subjects experienced freezes during turning. 69% of freezes occurred during the middle third of the turn. Turn-freezers had more severe spatiotemporal gait deficits. SIGNIFICANCE: Developing targeted therapies to retrain subjects to plant their whole foot on the ground with more consistency could help decrease episodes of freezing of gait.

Olfactory Deficits in the Freezing of Gait Phenotype of Parkinson's Disease.

Background: Olfactory dysfunction often occurs before motor onset in Parkinson's disease (PD) and can be detected with the University of Pennsylvania Smell Identification Test (UPSIT). Based on the Braak hypothesis, the olfactory bulb is one of two sites where disease pathology may start and spread to deeper brain structures. Objective: To evaluate whether a specific pattern of odorant identification on the UPSIT discriminated Parkinson's disease patients with and without freezing of gait. Methods: One hundred and twenty four consecutive participants (33 controls, 31 non-freezers, and 60 freezers) were administered the UPSIT. Using the chi-square test, each odorant on the UPSIT was ranked based on the differential ability of freezers and non-freezers to identify them correctly. Using predictive statistics and confusion matrices, the best combination of odorants and a cut-off score was determined. Results: Freezers had a shift toward a more severe hyposmia classification based on age and sex based normative values. The correct identification of nine odors (bubblegum, chocolate, smoke, wintergreen, paint thinner, orange, strawberry, grass, and peanut) was significantly worse in freezers compared to non-freezers. Correctly identifying ≤ 2 out of 3-odorants (bubblegum, chocolate, and smoke) had a 77% sensitivity and 61% specificity for categorizing freezers. The 3-odorant score was not correlated with disease duration, motor or total UPDRS scores, MoCA scores or age at testing. The predictive statistics were similar when sexes were separately categorized. Conclusions: A 3-odorant score helped categorize freezers and non-freezers with similar sensitivity and specificity to short odorant Parkinson's disease identification batteries.

Utility of objective gait measures in levodopa-unresponsive freezing in Parkinson's.

Levodopa-unresponsive gait freezing in Parkinson disease is debilitating. Gait kinematics, while time-consuming, can help optimize levodopa's benefit on gait stride length and stride velocity, and thereby improve freezing and falls in these patients.

Semantic Integration of Multi-Modal Data and Derived Neuroimaging Results Using the Platform for Imaging in Precision Medicine (PRISM) in the Arkansas Imaging Enterprise System (ARIES).

Neuroimaging is among the most active research domains for the creation and management of open-access data repositories. Notably lacking from most data repositories are integrated capabilities for semantic representation. The Arkansas Imaging Enterprise System (ARIES) is a research data management system which features integrated capabilities to support semantic representations of multi-modal data from disparate sources (imaging, behavioral, or cognitive assessments), across common image-processing stages (preprocessing steps, segmentation schemes, analytic pipelines), as well as derived results (publishable findings). These unique capabilities ensure greater reproducibility of scientific findings across large-scale research projects. The current investigation was conducted with three collaborating teams who are using ARIES in a project focusing on neurodegeneration. Datasets included magnetic resonance imaging (MRI) data as well as non-imaging data obtained from a variety of assessments designed to measure neurocognitive functions (performance scores on neuropsychological tests). We integrate and manage these data with semantic representations based on axiomatically rich biomedical ontologies. These instantiate a knowledge graph that combines the data from the study cohorts into a shared semantic representation that explicitly accounts for relations among the entities that the data are about. This knowledge graph is stored in a triple-store database that supports reasoning over and querying these integrated data. Semantic integration of the non-imaging data using background information encoded in biomedical domain ontologies has served as a key feature-engineering step, allowing us to combine disparate data and apply analyses to explore associations, for instance, between hippocampal volumes and measures of cognitive functions derived from various assessment instruments.

Differential Gait Decline in Parkinson's Disease Enhances Discrimination of Gait Freezers from Non-Freezers.

BACKGROUND: Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) for which treatments are limited. To develop neuroprotective strategies, determining whether disease progression is different in phenotypic variants of PD is essential. OBJECTIVE: To determine if freezers have a faster decline in spatiotemporal gait parameters. METHODS: Subjects were enrolled in a longitudinal study and assessed every 3- 6 months. Continuous gait in the levodopa ON-state was collected using a gait mat (Protokinetics). The slope of change/year in spatiotemporal gait parameters was calculated. RESULTS: 26 freezers, 31 non-freezers, and 25 controls completed an average of 6 visits over 28 months. Freezers had a faster decline in mean stride-length, stride-velocity, swing-%, single-support-%, and variability in single-support-% compared to non-freezers (p < 0.05). Gait decline was not correlated with initial levodopa dose, duration of levodopa therapy, change in levodopa dose or change in Montreal Cognitive Assessment scores (p > 0.25). Gait progression parameters were required to obtain 95% accuracy in categorizing freezers and non-freezers groups in a forward step-wise binary regression model. Change in mean stride-length, mean stride-width, and swing-% variability along with initial foot-length variability, mean swing-% and apathy scores were significant variables in the model. CONCLUSION: Freezers had a faster temporal decline in objectively quantified gait, and inclusion of longitudinal gait changes in a binary regression model greatly increased categorization accuracy. Levodopa dosing, cognitive decline and disease severity were not significant in our model. Early detection of this differential decline may help define freezing prone groups for testing putative treatments.

Lidocaine tripotassium phosphate complex laden microemulsion for prolonged local anaesthesia: In vitro and in vivo studies.

Lidocaine is widely used as a local anaesthetic in the clinical practice to manage pre- and post-operative pain, skin burns, etc. However, the short duration of action (< 2 h) of marketed dosage forms limit their ability to meet clinical needs. Herein, we prepared a lidocaine-tPP(tri potassium phosphate)-complex loaded microemulsion to achieve greater penetration, followed by destabilization of microemulsion in the skin layer to precipitate oil-complex to produce a depot effect in the skin for prolonging the effects of anaesthesia. The lidocaine-tPP-complex-microemulsion was compared with lidocaine base loaded microemulsion, marketed ointment USP and lidocaine HCl. The pseudo ternary phase diagrams at three Smix ratios (1:2, 1:3 and 1:4; Pluronic F127: PEG 400) were constructed using Capmul MCM C8 EP as oil phase. The Smix at 1:4 ratio showed large microemulsion area in comparison to 1:2 and 1:6 ratio. The lidocaine base (LD-1:4-ME10O45SM and LD-1:4-ME20O45SM) and lidocaine-tPP-complex (LDC-1:4-ME10O45SM and LDC-1:4-ME20O45SM) loaded microemulsion batches (1:4 ratio) were thermodynamically stable. The ex vivo diffusion study showed sustained release up to 12 h with microemulsion batches, in comparison to lidocaine HCl (4 h) and ointment base (7 h). The selected LDC-1:4-ME20O45SM batch was non-irritating on the rabbit skin. In drug retention studies, LD-1:4-ME20O45SM and LDC-1:4-ME20O45SM batches showed 2.68- and 3.93-fold greater lidocaine retention in comparison to ointment USP. The radiant heat tail-flick test showed prolong local anaesthesia using LDC-1:4-ME20O45SM in comparison to ointment USP. The findings suggest that lidocaine-tPP-complex loaded microemulsion could be a potential strategy for providing prolong local anaesthesia.

Objective impairment of tandem gait in Parkinson's disease patients increases with disease severity.

INTRODUCTION: Tandem gait abnormalities have been reported to increase with advancing age, play a role in fall-prediction in Parkinson's disease, and distinguish it from atypical parkinsonism. Tandem gait has been scored based on the number of side steps off a straight line in these studies. Objective measurement of spatiotemporal tandem gait parameters in Parkinson's disease has not been previously reported. METHODS: Subjects (74 Parkinson's disease and 28 controls) were enrolled after IRB approval. Those with more than 1 fall/day or a Montreal Cognitive Assessment score <10 were excluded. Subjects tandem walked ("heel to toe") on a 20 foot pressure-sensor mat. Data was collected and analyzed using PKMAS software (Protokinetics). RESULTS: Compared to controls, on tandem gait, Parkinson's subjects had increased step width, stride width and path width, with a slower stride velocity and an increased time spent in all phases of the gait cycle. Parkinson's subjects also applied greater pressure with each step and had greater step-to-step variability in tandem gait measures. While Hoehn & Yahr stage 1 subjects were not significantly different from controls, stage 2 and 2.5 + groups were different. Parkinson's subjects with freezing of gait also walked with a wider base compared to those without gait freezing. Tandem gait spatiotemporal parameters were not correlated with fall frequency. CONCLUSIONS: Tandem gait is impaired in Parkinson's disease in a stage-dependent manner, with wider base and increased step-to-step variability, which could suggest involvement of cerebellar and mediolateral balance pathways.