No Measurable Transfer of Oxytocin-Receptor Agonist Merotocin Detected in Human Breast Milk.

Objective: The study aimed to assess the transfer of merotocin from systemic circulation to breast milk in early postpartum women and women with established lactation. Methods: This was a two-part, multicenter, open-label, parallel-group study. Merotocin was administered as a single 90-minute intravenous (iv) infusion mimicking the intranasal pharmacokinetic profile. In Part A, 12 early postpartum women received doses of either 4 µg (n = 6) or 16 µg (n = 6) of merotocin within 4 days of delivery. In Part B, six women with established lactation received 20 µg of merotocin. The total concentration of merotocin in plasma and breast milk and its metabolites excreted in breast milk were measured at various time points. Adverse events (AEs) were also assessed for both parts of the study. Results: In both early postpartum and established lactation groups (mean age, 26.3 years; 83.3% Caucasian), merotocin and its metabolites in breast milk were below the limit of quantification (25.0 pg/mL) at all time points. Sixteen treatment-emergent AEs occurred in early postpartum women only, including seven events of uterine spasm and three of breast engorgement. There was one moderate event, whereas all the other events were considered mild. Conclusion: Merotocin was undetectable in breast milk after single iv administration of up to 20 µg in early postpartum women and women with established lactation.

Alleviating anxiety while breastfeeding: evaluating buspirone transfer into human milk.

PURPOSE: Buspirone, an anxiolytic with minimal risk of dependence or respiratory depression, lacks extensive published data on its transfer into human milk during lactation. The objective of this study was to 1) quantify the transfer of buspirone and its active metabolite 1-pyrimidinylpiperazine (1-PP) into human milk, allowing for an estimation of maternal drug exposure to the breastfed infant, and 2) report observations of the infants exposed to buspirone via breastmilk. METHODS: Milk samples and health histories were collected from nine lactating mothers who donated milk samples to the InfantRisk Human Milk Biorepository while taking buspirone. The drug concentration-time profile of buspirone and 1-PP was determined using liquid chromatography-mass spectrometry. RESULTS: Buspirone was below the detection level of 1.5 ng/mL in all milk samples with dosages ranging from 7.5 to 30 mg twice daily. However, low levels of active metabolite 1-PP were observed at 7.5 mg twice daily up to 30 mg twice daily. The relative infant dose (RID) calculated ranged from 0.21 to 2.17%, which is below the standard 10% threshold for infant safety. There were no reports of adverse effects in the exposed infants. CONCLUSION: The levels of buspirone observed in all participants' milk samples were exceedingly low. The subsequently low relative infant dose (RID) in the range of 0.21% to 2.17% is below the 10% threshold for infant safety, suggesting that the transfer of maternal buspirone and its active metabolite (1-PP) into human milk is clinically insignificant and poses minimal risk to a breastfed infant.

Soft robotic apparel to avert freezing of gait in Parkinson's disease.

Freezing of gait (FoG) is a profoundly disruptive gait disturbance in Parkinson's disease, causing unintended stops while walking. Therapies for FoG reveal modest and transient effects, resulting in a lack of effective treatments. Here we show proof of concept that FoG can be averted using soft robotic apparel that augments hip flexion. The wearable garment uses cable-driven actuators and sensors, generating assistive moments in concert with biological muscles. In this n-of-1 trial with five repeated measurements spanning 6 months, a 73-year-old male with Parkinson's disease and substantial FoG demonstrated a robust response to robotic apparel. With assistance, FoG was instantaneously eliminated during indoor walking (0% versus 39 ± 16% time spent freezing when unassisted), accompanied by 49 ± 11 m (+55%) farther walking compared to unassisted walking, faster speeds (+0.18 m s-1) and improved gait quality (-25% in gait variability). FoG-targeting effects were repeatable across multiple days, provoking conditions and environment contexts, demonstrating potential for community use. This study demonstrated that FoG was averted using soft robotic apparel in an individual with Parkinson's disease, serving as an impetus for technological advancements in response to this serious yet unmet need.

Individualized Learning-Based Ground Reaction Force Estimation in People Post-Stroke Using Pressure Insoles.

Stroke is a leading cause of gait disability that leads to a loss of independence and overall quality of life. The field of clinical biomechanics aims to study how best to provide rehabilitation given an individual's impairments. However, there remains a disconnect between assessment tools used in biomechanical analysis and in clinics. In particular, 3-dimensional ground reaction forces (3D GRFs) are used to quantify key gait characteristics, but require lab-based equipment, such as force plates. Recent efforts have shown that wearable sensors, such as pressure insoles, can estimate GRFs in real-world environments. However, there is limited understanding of how these methods perform in people post-stroke, where gait is highly heterogeneous. Here, we evaluate three subject-specific machine learning approaches to estimate 3D GRFs with pressure insoles in people post-stroke across varying speeds. We find that a Convolutional Neural Network-based approach achieves the lowest estimation errors of 0.75 ± 0.24, 1.13 ± 0.54, and 4.79 ± 3.04 % bodyweight for the medio-lateral, antero-posterior, and vertical GRF components, respectively. Estimated force components were additionally strongly correlated with the ground truth measurements ( ). Finally, we show high estimation accuracy for three clinically relevant point metrics on the paretic limb. These results suggest the potential for an individualized machine learning approach to translate to real-world clinical applications.

Effects of high-intensity gait training with and without soft robotic exosuits in people post-stroke: a development-of-concept pilot crossover trial.

INTRODUCTION: High-intensity gait training is widely recognized as an effective rehabilitation approach after stroke. Soft robotic exosuits that enhance post-stroke gait mechanics have the potential to improve the rehabilitative outcomes achieved by high-intensity gait training. The objective of this development-of-concept pilot crossover study was to evaluate the outcomes achieved by high-intensity gait training with versus without soft robotic exosuits. METHODS: In this 2-arm pilot crossover study, four individuals post-stroke completed twelve visits of speed-based, high-intensity gait training: six consecutive visits of Robotic Exosuit Augmented Locomotion (REAL) gait training and six consecutive visits without the exosuit (CONTROL). The intervention arms were counterbalanced across study participants and separated by 6 + weeks of washout. Walking function was evaluated before and after each intervention using 6-minute walk test (6MWT) distance and 10-m walk test (10mWT) speed. Moreover, 10mWT speeds were evaluated before each training visit, with the time-course of change in walking speed computed for each intervention arm. For each participant, changes in each outcome were compared to minimal clinically-important difference (MCID) thresholds. Secondary analyses focused on changes in propulsion mechanics and associated biomechanical metrics. RESULTS: Large between-group effects were observed for 6MWT distance (d = 1.41) and 10mWT speed (d = 1.14). REAL gait training resulted in an average pre-post change of 68 ± 27 m (p = 0.015) in 6MWT distance, compared to a pre-post change of 30 ± 16 m (p = 0.035) after CONTROL gait training. Similarly, REAL training resulted in a pre-post change of 0.08 ± 0.03 m/s (p = 0.012) in 10mWT speed, compared to a pre-post change of 0.01 ± 06 m/s (p = 0.76) after CONTROL. For both outcomes, 3 of 4 (75%) study participants surpassed MCIDs after REAL training, whereas 1 of 4 (25%) surpassed MCIDs after CONTROL training. Across the training visits, REAL training resulted in a 1.67 faster rate of improvement in walking speed. Similar patterns of improvement were observed for the secondary gait biomechanical outcomes, with REAL training resulting in significantly improved paretic propulsion for 3 of 4 study participants (p < 0.05) compared to 1 of 4 after CONTROL. CONCLUSION: Soft robotic exosuits have the potential to enhance the rehabilitative outcomes produced by high-intensity gait training after stroke. Findings of this development-of-concept pilot crossover trial motivate continued development and study of the REAL gait training program.

Pharmacokinetics of Ketamine Transfer Into Human Milk.

PURPOSE/BACKGROUND: Ketamine is an N -methyl- d -aspartate-antagonistic dissociative anesthetic infused intermittently for off-label management of treatment-resistant depression, acute suicidality, and postpartum depression. Despite the prevalence of postpartum depression nearing upward of 15% of deliveries, almost no research has been done to evaluate its safety during lactation. METHODS: In this study, human milk samples were released from the InfantRisk Center's Human Milk Biorepository of 4 participants treated with intermittent ketamine infusions (49-378 mg) to determine the levels of the drug and its active norketamine metabolite using liquid chromatography-mass spectrometry. RESULTS: The absolute infant dose of ketamine from human milk was 0.003 to 0.017 mg/kg per day, and norketamine was 0.005 to 0.018 mg/kg per day. The relative infant dose (RID) for ketamine ranged from 0.34% to 0.57%. The RID for norketamine ranged from 0.29% to 0.95%. There were no reported infant adverse effects. CONCLUSION: The findings of this study suggest that the transfer of ketamine, as well as its active metabolite, norketamine, into human milk is minimal, as estimated by RIDs less than 1% in all participants. These relative doses are well below standardly accepted safety thresholds.

Effects of a soft robotic exosuit on the quality and speed of overground walking depends on walking ability after stroke.

BACKGROUND: Soft robotic exosuits can provide partial dorsiflexor and plantarflexor support in parallel with paretic muscles to improve poststroke walking capacity. Previous results indicate that baseline walking ability may impact a user's ability to leverage the exosuit assistance, while the effects on continuous walking, walking stability, and muscle slacking have not been evaluated. Here we evaluated the effects of a portable ankle exosuit during continuous comfortable overground walking in 19 individuals with chronic hemiparesis. We also compared two speed-based subgroups (threshold: 0.93 m/s) to address poststroke heterogeneity. METHODS: We refined a previously developed portable lightweight soft exosuit to support continuous overground walking. We compared five minutes of continuous walking in a laboratory with the exosuit to walking without the exosuit in terms of ground clearance, foot landing and propulsion, as well as the energy cost of transport, walking stability and plantarflexor muscle slacking. RESULTS: Exosuit assistance was associated with improvements in the targeted gait impairments: 22% increase in ground clearance during swing, 5° increase in foot-to-floor angle at initial contact, and 22% increase in the center-of-mass propulsion during push-off. The improvements in propulsion and foot landing contributed to a 6.7% (0.04 m/s) increase in walking speed (R2 = 0.82). This enhancement in gait function was achieved without deterioration in muscle effort, stability or cost of transport. Subgroup analyses revealed that all individuals profited from ground clearance support, but slower individuals leveraged plantarflexor assistance to improve propulsion by 35% to walk 13% faster, while faster individuals did not change either. CONCLUSIONS: The immediate restorative benefits of the exosuit presented here underline its promise for rehabilitative gait training in poststroke individuals.

Ankle-targeted exosuit resistance increases paretic propulsion in people post-stroke.

BACKGROUND: Individualized, targeted, and intense training is the hallmark of successful gait rehabilitation in people post-stroke. Specifically, increasing use of the impaired ankle to increase propulsion during the stance phase of gait has been linked to higher walking speeds and symmetry. Conventional progressive resistance training is one method used for individualized and intense rehabilitation, but often fails to target paretic ankle plantarflexion during walking. Wearable assistive robots have successfully assisted ankle-specific mechanisms to increase paretic propulsion in people post-stroke, suggesting their potential to provide targeted resistance to increase propulsion, but this application remains underexamined in this population. This work investigates the effects of targeted stance-phase plantarflexion resistance training with a soft ankle exosuit on propulsion mechanics in people post-stroke. METHODS: We conducted this study in nine individuals with chronic stroke and tested the effects of three resistive force magnitudes on peak paretic propulsion, ankle torque, and ankle power while participants walked on a treadmill at their comfortable walking speeds. For each force magnitude, participants walked for 1 min while the exosuit was inactive, 2 min with active resistance, and 1 min with the exosuit inactive, in sequence. We evaluated changes in gait biomechanics during the active resistance and post-resistance sections relative to the initial inactive section. RESULTS: Walking with active resistance increased paretic propulsion by more than the minimal detectable change of 0.8 %body weight at all tested force magnitudes, with an average increase of 1.29 ± 0.37 %body weight at the highest force magnitude. This improvement corresponded to changes of 0.13 ± 0.03 N m kg- 1 in peak biological ankle torque and 0.26 ± 0.04 W kg- 1 in peak biological ankle power. Upon removal of resistance, propulsion changes persisted for 30 seconds with an improvement of 1.49 ± 0.58 %body weight after the highest resistance level and without compensatory involvement of the unresisted joints or limb. CONCLUSIONS: Targeted exosuit-applied functional resistance of paretic ankle plantarflexors can elicit the latent propulsion reserve in people post-stroke. After-effects observed in propulsion highlight the potential for learning and restoration of propulsion mechanics. Thus, this exosuit-based resistive approach may offer new opportunities for individualized and progressive gait rehabilitation.

Design and evaluation of an independent 4-week, exosuit-assisted, post-stroke community walking program.

Chronic impairment in the paretic ankle following stroke often requires that individuals use compensatory patterns such as asymmetric propulsion to achieve effective walking speeds needed for community engagement. Ankle exosuit assistance can provide ankle biomechanical benefit in the lab, but such environments inherently limit the amount of practice available. Community walking studies without exosuits can provide massed practice and benefit walking speed but are limited in their ability to assist proper mechanics. In this study, we combined the positive aspects of community training with those of exosuit assistance. We developed and evaluated a community Robotic Exosuit Augmented Locomotion (cREAL) program. Four participants in the chronic stage of stroke independently used our community ankle exosuit for walking in the community 3-5 days/week for 4 weeks. We performed lab evaluations before and after the 4-week program. Two participants significantly improved their unassisted paretic propulsion by an average of 27% after the program and walked on average 4001 steps/day more in the week following the program. Despite the small number of participants, this study provides preliminary evidence for the potential of exosuits to augment gait training and rehabilitation in the community.

Natural Walking Intensity in Persons With Parkinson Disease.

BACKGROUND AND PURPOSE: Few persons with Parkinson disease (PD) appear to engage in moderate-intensity walking associated with disease-modifying health benefits. How much time is spent walking at lower, yet still potentially beneficial, intensities is poorly understood. The purpose of this exploratory, observational study was to describe natural walking intensity in ambulatory persons with PD. METHODS: Accelerometer-derived real-world walking data were collected for more than 7 days at baseline from 82 participants enrolled in a PD clinical trial. Walking intensity was defined according to the number of steps in each active minute (1-19, 20-39, 40-59, 60-79, 80-99, or ≥100 steps). Daily minutes of walking and duration of the longest sustained walking bout were calculated at each intensity. Number of sustained 10 to 19, 20 to 29, and 30-minute bouts and greater at any intensity also were calculated. Values were analyzed in the context of physical activity guidelines. RESULTS: Most daily walking occurred at lower intensities (157.3 ± 58.1 min of 1-19 steps; 81.3 ± 32.6 min of 20-39 steps; 38.2 ± 21.3 min of 40-59 steps; 15.1 ± 11.5 min of 60-79 steps; 7.4 ± 7.0 min of 80-99 steps; 7.3 ± 9.6 min of ≥100 steps). The longest daily sustained walking bout occurred at the lowest intensity level (15.9 ± 5.2 min of 1-19 steps). Few bouts lasting 20 minutes and greater occurred at any intensity. DISCUSSION AND CONCLUSIONS: Despite relatively high daily step counts, participants tended to walk at remarkably low intensity, in bouts of generally short duration, with relatively few instances of sustained walking. The findings reinforced the need for health promotion interventions designed specifically to increase walking intensity.Video Abstract available for more insight from authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A426 ).

Progesterone for women with threatened miscarriage (STOP trial): a placebo-controlled randomized clinical trial.

STUDY QUESTION: In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? SUMMARY ANSWER: In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates. WHAT IS KNOWN ALREADY: Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit. STUDY DESIGN, SIZE, DURATION: We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women. PARTICIPANTS/MATERIALS, SETTING, METHODS: This trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group. MAIN RESULTS AND THE ROLE OF CHANCE: The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes. LIMITATIONS, REASONS FOR CAUTION: Our study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis. WIDER IMPLICATIONS OF THE FINDINGS: We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research. STUDY FUNDING/COMPETING INTEREST(S): Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work. TRIAL REGISTRATION NUMBER: ACTRN12611000405910. TRIAL REGISTRATION DATE: 19 April 2011. DATE OF FIRST PATIENT'S ENROLMENT: 06 February 2012.

Vulvovaginal erosive lichen planus refractory to topical therapies: What's next? A case report.

A 60-year-old woman was referred for progressive and severe vulvovaginal pain characterized by erosions and Wickham's stria for the past 7 months. Her condition had not responded to oral fluconazole, topical estrogen cream, and topical clobetasol cream. Vulvar and vaginal biopsies were obtained under general anesthesia to verify the diagnosis of erosive lichen planus given the failed response to ultrapotent topical steroids. Tacrolimus cream was added but not tolerated. Oral and cutaneous lesions of lichen planus also developed. In the absence of evidence-based guidelines, three different systemic treatments were administered sequentially (hydroxychloroquine, mycophenolate, and finally cyclosporin) before a satisfactory, well-tolerated, and sustained clinical response was obtained. Topical betamethasone ointment in a taper was continued to assist in sustaining a vulvovaginal response after cyclosporin was discontinued.

Does clinically measured walking capacity contribute to real-world walking performance in Parkinson's disease?

OBJECTIVE: The study examined how clinically measured walking capacity contributes to real-world walking performance in persons with Parkinson's disease (PD). METHODS: Cross-sectional baseline data (n = 82) from a PD clinical trial were analyzed. The 6-Minute Walk Test (6MWT) and 10-Meter Walk Test (10MWT) were used to generate capacity metrics of walking endurance and fast gait speed, respectively. An activity monitor worn for seven days was used to generate performance metrics of mean daily steps and weekly moderate intensity walking minutes. Univariate linear regression analyses were used to examine associations between each capacity and performance measure in the full sample and less and more active subgroups. RESULTS: Walking capacity significantly contributed to daily steps in the full sample (endurance: R2=.13, p < .001; fast gait speed: R2=.07, p = .017) and in the less active subgroup (endurance: R2 =.09, p = .045). Similarly, walking capacity significantly contributed to weekly moderate intensity minutes in the full sample (endurance: R2=.13, p < .001; fast gait speed: R2=.09, p = .007) and less active subgroup (endurance: R2 = .25, p < .001; fast gait speed: R2 =.21, p = .007). Walking capacity did not significantly contribute to daily steps or moderate intensity minutes in the more active subgroup. CONCLUSIONS: Walking capacity contributed to, but explained a relatively small portion of the variance in, real-world walking performance. The contribution was somewhat greater in less active individuals. The study adds support to the idea that clinically measured walking capacity may have limited benefit for understanding real-world walking performance in PD. Factors beyond walking capacity may better account for actual walking behavior.

Human Milk and Plasma Pharmacokinetics of Single-Dose Rimegepant 75 mg in Healthy Lactating Women.

Objective: Investigate whether rimegepant-an oral small molecule calcitonin gene-related peptide receptor antagonist for the treatment of migraine-is excreted in human milk after a single 75 mg dose and characterize its concentration-time profile in the plasma and milk of healthy lactating women to determine the relative infant dose (RID). Methods: This open-label, single-center study enrolled healthy lactating women aged 18-40 years with a gestation of 37-42 weeks and uncomplicated delivery of a single healthy child ≥2 weeks (14 days) and ≤6 months before study drug administration. Plasma samples were collected 0, 1, 2, 4, and 8 hours postdose; human milk samples were collected at 0, 1, 2, 4, 8, 12, 16, 24, 32, and 36 hours. The milk:plasma drug concentration ratio was estimated as the ratio of the human milk:plasma areas under the curve. The RID (%) was calculated as 100 times the quotient of the body weight-normalized infant and maternal doses. Results: Subjects (N = 12) were enrolled between 25 January and 15 September 2020. The mean (standard deviation [SD]) age was 29.8 (3.6) years; mean (SD) body mass index was 26.8 (4.9) kg/m2. The mean (SD) RID of rimegepant was 0.51% (0.14). The mean (SD) body-weight normalized infant dose was 0.005 (0.001) mg/kg/day, the mean (SD) body-weight normalized maternal dose was 1.04 (0.18) mg/kg/day, and mean (SD) maternal body weight was 74.0 (13.3) kg. Conclusion: On a weight-adjusted basis, the mean RID of rimegepant was <1% of the maternal dose.

Mode of Cannabis Use and Factors Related to Frequency of Cannabis Use Among Breastfeeding Mothers: Results from an Online Survey.

Background: In the United States, 5% of breastfeeding mothers report using cannabis. Frequent cannabis use results in higher delta-9-tetrahydrocannabinol (THC) in breast milk, and mode of cannabis use may also impact risk to the infant. The aim of this study was to understand how breastfeeding mothers use cannabis and factors related to frequency of its use. Methods: An anonymous online survey was conducted among mothers who used cannabis while breastfeeding. Frequency of cannabis use was ascertained along with modes of and reasons for cannabis use. Respondents were grouped by frequency of use: less-than-daily (n = 686), low-daily (1-3 times/day; n = 423), and high-daily (≥4 times/day; n = 218). Chi-square and analysis of variance tested between-group differences, and ordinal logistic regression examined factors associated with cannabis use frequency. Results: Smoking (88%) was the most common mode of cannabis consumption, followed by vaping (48%) and oral/edibles (36%). Smoking and vaping differed by cannabis use frequency. Only 54% used cannabis to get high, but was reported more among frequent users. In contrast, 89% of mothers used cannabis for mental or physical health symptoms, including anxiety, depression, gastrointestinal symptoms, chronic pain, and posttraumatic stress disorder. These symptoms differed by cannabis use frequency. Reporting more symptoms was associated with higher frequency of use. The odds of increasing cannabis use frequency was 2.7 for those reporting 1-2 health reasons, 5.6 for those reporting 3-4 health reasons, and 13.1 for reporting ≥5 health reasons. Conclusions: Strategies are needed to address maternal mental and physical health, which may be key to reducing cannabis use among breastfeeding mothers.

Targeting Paretic Propulsion and Walking Speed With a Soft Robotic Exosuit: A Consideration-of-Concept Trial.

Background: Soft robotic exosuits can facilitate immediate increases in short- and long-distance walking speeds in people with post-stroke hemiparesis. We sought to assess the feasibility and rehabilitative potential of applying propulsion-augmenting exosuits as part of an individualized and progressive training program to retrain faster walking and the underlying propulsive strategy. Methods: A 54-yr old male with chronic hemiparesis completed five daily sessions of Robotic Exosuit Augmented Locomotion (REAL) gait training. REAL training consists of high-intensity, task-specific, and progressively challenging walking practice augmented by a soft robotic exosuit and is designed to facilitate faster walking by way of increased paretic propulsion. Repeated baseline assessments of comfortable walking speed over a 2-year period provided a stable baseline from which the effects of REAL training could be elucidated. Additional outcomes included paretic propulsion, maximum walking speed, and 6-minute walk test distance. Results: Comfortable walking speed was stable at 0.96 m/s prior to training and increased by 0.30 m/s after training. Clinically meaningful increases in maximum walking speed (Δ: 0.30 m/s) and 6-minute walk test distance (Δ: 59 m) were similarly observed. Improvements in paretic peak propulsion (Δ: 2.80 %BW), propulsive power (Δ: 0.41 W/kg), and trailing limb angle (Δ: 6.2 degrees) were observed at comfortable walking speed (p's < 0.05). Likewise, improvements in paretic peak propulsion (Δ: 4.63 %BW) and trailing limb angle (Δ: 4.30 degrees) were observed at maximum walking speed (p's < 0.05). Conclusions: The REAL training program is feasible to implement after stroke and capable of facilitating rapid and meaningful improvements in paretic propulsion, walking speed, and walking distance.

Real-time gait metric estimation for everyday gait training with wearable devices in people poststroke.

Hemiparetic walking after stroke is typically slow, asymmetric, and inefficient, significantly impacting activities of daily living. Extensive research shows that functional, intensive, and task-specific gait training is instrumental for effective gait rehabilitation, characteristics that our group aims to encourage with soft robotic exosuits. However, standard clinical assessments may lack the precision and frequency to detect subtle changes in intervention efficacy during both conventional and exosuit-assisted gait training, potentially impeding targeted therapy regimes. In this paper, we use exosuit-integrated inertial sensors to reconstruct three clinically meaningful gait metrics related to circumduction, foot clearance, and stride length. Our method corrects sensor drift using instantaneous information from both sides of the body. This approach makes our method robust to irregular walking conditions poststroke as well as usable in real-time applications, such as real-time movement monitoring, exosuit assistance control, and biofeedback. We validate our algorithm in eight people poststroke in comparison to lab-based optical motion capture. Mean errors were below 0.2 cm (9.9%) for circumduction, -0.6 cm (-3.5%) for foot clearance, and 3.8 cm (3.6%) for stride length. A single-participant case study shows our technique's promise in daily-living environments by detecting exosuit-induced changes in gait while walking in a busy outdoor plaza.

Human Milk Endocannabinoid Levels as a Function of Obesity and Diurnal Rhythm.

The endocannabinoid system is involved in the regulation of a variety of physiological and cognitive processes. While the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (N-arachidonoylethanolamine, AEA) have been found in breast milk, their role(s) have yet to be determined. This study determined the normal concentration ranges of endocannabinoids (2-AG and AEA) in breast milk and the influences, if any, of obesity and diurnal rhythms on their levels. Milk samples were collected from 36 breastfeeding mothers at 4-8 weeks postpartum at each feed over a 24-h period, and further stratified into three groups based on body mass index (BMI). The samples were analyzed using liquid chromatography mass spectrometry. AEA was below the limit of detection and 2-AG levels averaged 59.3 ± 18.3 ng/mL (± SD) in women with normal BMI. Wide-ranging 2-AG concentrations in the overweight (65.5 ± 41.9 ng/mL) /obese (66.1 ± 40.6 ng/mL) groups suggest BMI may be a contributing factor influencing its levels. Following a diurnal pattern, there was a significantly higher 2-AG concentration observed during the day, as compared to night time samples. In conclusion, our study clearly suggests that appropriate milk collection and storage conditions are critical. Further, body weight and diurnal rhythm appear to influence levels of 2-AG. Based on these results, future studies are underway to determine what specific roles endocannabinoids may play in human milk and how elevated levels of 2-AG may modulate infant appetite and health.

Dexmedetomidine Levels in Breast Milk: Analysis of Breast Milk Expressed During and After Awake Craniotomy.

Background: Dexmedetomidine is an α2-adrenoreceptor agonist with utility in sedation and analgesia for the perioperative or intensive care patient. The literature regarding the safety of dexmedetomidine in lactating patients is very limited. Methods: We present a case of a lactating patient who received dexmedetomidine bolus and infusion as part of her intraoperative sedation during an awake craniotomy. Breast milk samples were expressed by the patient twice intraoperatively and twice postoperatively. All samples collected were analyzed using liquid chromatography mass spectrometry. Results: Dexmedetomidine concentrations in the breast milk were measured at various intervals and were 88 and 50 pg/mL intraoperatively, and 89 and 15 pg/mL postoperatively. Conclusion: Levels of dexmedetomidine in breast milk were exceedingly low. Interruption of breastfeeding and/or discarding expressed breast milk may not be necessary after dexmedetomidine in breastfeeding mothers. Further investigation with a larger sample size is warranted to describe safety profile of dexmedetomidine in breastfeeding infants.

Are Mobile Persons With Parkinson Disease Necessarily More Active?

BACKGROUND AND PURPOSE: Walking activity in persons with Parkinson disease (PD) is important for preventing functional decline. The contribution of walking activity to home and community mobility in PD is poorly understood. METHODS: Cross-sectional baseline data (N = 69) were analyzed from a randomized controlled PD trial. The Life-Space Assessment (LSA) quantified the extent, frequency, and independence across 5 expanding levels of home and community mobility, producing individual subscores and a total score. Two additional summed scores were used to represent mobility within (Levels 1-3) and beyond (Levels 4-5) neighborhood limits. An accelerometer measured walking activity for 7 days. Regression and correlation analyses evaluated relationships between daily steps and mobility scores. Mann-Whitney U tests secondarily compared differences in mobility scores between the active and sedentary groups. RESULTS: Walking activity contributed significantly to the summed Level 1-3 score (ß = 0.001, P = 0.004) but not to the summed Level 4-5 (ß = 0.001, P = 0.33) or total (ß = 0.002, P = 0.07) scores. Walking activity was significantly related to Level 1 (ρ = 0.336, P = 0.005), Level 2 (ρ = 0.307, P = 0.010), and Level 3 (ρ = 0.314, P = 0.009) subscores. Only the summed Level 1-3 score (P = 0.030) was significantly different between the active and sedentary groups. DISCUSSION AND CONCLUSIONS: Persons with PD who demonstrated greater mobility beyond the neighborhood were not necessarily more active; walking activity contributed more so to home and neighborhood mobility. Compared with LSA total score, the Level 1-3 summed score may be a more useful participation-level measure for assessing the impact of changes in walking activity.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A349).