Concurrent brain-responsive and vagus nerve stimulation for treatment of drug-resistant focal epilepsy.

OBJECTIVE: Clinical trials of a brain-responsive neurostimulator, RNS® System (RNS), excluded patients with a vagus nerve stimulator, VNS® System (VNS). The goal of this study was to evaluate seizure outcomes and safety of concurrent RNS and VNS stimulation in adults with drug-resistant focal-onset seizures. METHODS: A retrospective multicenter chart review was performed on all patients with an active VNS and RNS who were treated for a minimum of 6 months with both systems concurrently. Frequency of disabling seizures at baseline before RNS, at 1 year after RNS placement, and at last follow-up were used to calculate the change in seizure frequency after treatment. Data on adverse events and complications related to each device were collected. RESULTS: Sixty-four patients from 10 epilepsy centers met inclusion criteria. All but one patient received RNS after VNS. The median follow-up time after RNS implantation was 28 months. Analysis of the entire population of patients with active VNS and RNS systems revealed a median reduction in seizure frequency at 1 year post-RNS placement of 43% with a responder rate of 49%, and at last follow-up a 64% median reduction with a 67% responder rate. No negative interactions were reported from the concurrent use of VNS and RNS. Stimulation-related side-effects were reported more frequently in association with VNS (30%) than with RNS (2%). SIGNIFICANCE: Our findings suggest that concurrent treatment with VNS and RNS is safe and that the addition of RNS to VNS can further reduce seizure frequency.

Seizure outcome with responsive neurostimulation (RNS) comparing strip versus depth leads.

OBJECTIVE: This study aimed to compare seizure outcomes and complication rates in patients treated with only responsive neurostimulation (RNS) strip leads with those treated with only RNS depth leads. METHODS: A retrospective cohort study was performed using the institutional epilepsy surgery database. Included was any patient implanted with the RNS system between August 2015 and May 2018 with either two depth (2D) or two strip (2S) leads connected to the device and at least 6 months follow-up. Excluded were those with a combination of active depth and strip leads. Data extracted from the charts comprised demographic information, duration of epilepsy, presence of a magnetic resonance imaging (MRI) lesion, prior resective surgery, clinically disabling seizures at baseline and follow-up, prior invasive monitoring, location (mesial temporal or neocortical) and number of seizure foci, unilateral or bilateral RNS lead placement, and postoperative complications. RESULTS: Of 48 screened patients, 34 met study inclusion criteria. Of these, 15 were treated with 2D leads and 19 with 2S leads. Groups 2D and 2S were comparable with respect to age at onset, duration of epilepsy, baseline seizure frequency, and exposure time to RNS. After adjustment for patient age and duration of epilepsy, seizure frequency in 2S patients was noted to be decreased by 83% (p = 0.046), while it was reduced by 51% (p = 0.080) in 2D patients. The complication rate was not significantly different between the two groups. CONCLUSION: In our small retrospective population, patients with RNS strip leads experienced a significantly greater seizure reduction than patients with RNS depth leads, without a difference in complication rate.

RNS modifications to eliminate stimulation-triggered signs or symptoms (STS): Case series and practical guide.

Responsive neurostimulation (RNS) for intractable epilepsy involves placement of electrodes onto or into the brain that detect seizure activity and then deliver a current to abort a seizure before it spreads. Successful RNS treatment can deliver hundreds of stimulations per day, which are generally unnoticeable to patients. Uncommonly, RNS electrodes may result in stimulation of brain regions or peripheral structures that causes uncomfortable sensory or motor effects, a phenomenon we refer to as stimulation-triggered signs or symptoms (STS). Occurrence of STS may limit the ability to use RNS to full capacity to reduce seizures. In this case series, we describe STS in six out of 58 (10.3%) RNS patients at our institution. To eliminate or minimize STS, we developed a protocol for modification of RNS parameters. Modifying RNS stimulation was associated with reduced STS in all six patients, five had adjustment of stimulation settings, one of lead position. Five out of six patients were able to undergo further optimization of RNS for improved seizure control after reduction of symptoms. One patient had recurrent STS that prevented further increase of RNS stimulation current. This study may help other medical teams in identifying and reducing STS in patients with epilepsy receiving RNS devices.

Collective ratchet effects and reversals for active matter particles on quasi-one-dimensional asymmetric substrates.

Using computer simulations, we study a two-dimensional system of sterically interacting self-mobile run-and-tumble disk-shaped particles with an underlying periodic quasi-one-dimensional asymmetric substrate, and show that a rich variety of collective active ratchet behaviors arise as a function of particle density, activity, substrate period, and the maximum force exerted by the substrate. The net dc drift, or ratchet transport flux, is nonmonotonic since it increases with increased activity but is diminished by the onset of self-clustering of the active particles. Increasing the particle density decreases the ratchet transport flux for shallow substrates but increases the ratchet transport flux for deep substrates due to collective hopping events. At the highest particle densities, the ratchet motion is destroyed by a self-jamming effect. We show that it is possible to realize reversals of the direction of the net dc drift in the deep substrate limit when multiple rows of active particles can be confined in each substrate minimum, permitting emergent particle-like excitations to appear that experience an inverted effective substrate potential. We map out a phase diagram of the forward and reverse ratchet effects as a function of the particle density, activity, and substrate properties.

Structural transitions and hysteresis in clump- and stripe-forming systems under dynamic compression.

Using numerical simulations, we study the dynamical evolution of particles interacting via competing long-range repulsion and short-range attraction in two dimensions. The particles are compressed using a time-dependent quasi-one dimensional trough potential that controls the local density, causing the system to undergo a series of structural phase transitions from a low density clump lattice to stripes, voids, and a high density uniform state. The compression proceeds via slow elastic motion that is interrupted with avalanche-like bursts of activity as the system collapses to progressively higher densities via plastic rearrangements. The plastic events vary in magnitude from small rearrangements of particles, including the formation of quadrupole-like defects, to large-scale vorticity and structural phase transitions. In the dense uniform phase, the system compresses through row reduction transitions mediated by a disorder-order process. We characterize the rearrangement events by measuring changes in the potential energy, the fraction of sixfold coordinated particles, the local density, and the velocity distribution. At high confinements, we find power law scaling of the velocity distribution during row reduction transitions. We observe hysteresis under a reversal of the compression when relatively few plastic rearrangements occur. The decompressing system exhibits distinct phase morphologies, and the phase transitions occur at lower compression forces as the system expands compared to when it is compressed.

The addition of beta-hydroxy-beta-methylbutyrate and isomaltulose to whey protein improves recovery from highly demanding resistance exercise.

OBJECTIVE: This study evaluated whether a combination of whey protein (WP), calcium beta-hydroxy-beta-methylbutyrate (HMB), and carbohydrate exert additive effects on recovery from highly demanding resistance exercise. METHODS: Thirteen resistance-trained men (age: 22.6 ± 3.9 years; height: 175.3 ± 12.2 cm; weight: 86.2 ± 9.8 kg) completed a double-blinded, counterbalanced, within-group study. Subjects ingested EAS Recovery Protein (RP; EAS Sports Nutrition/Abbott Laboratories, Columbus, OH) or WP twice daily for 2 weeks prior to, during, and for 2 days following 3 consecutive days of intense resistance exercise. The workout sequence included heavy resistance exercise (day 1) and metabolic resistance exercise (days 2 and 3). The subjects performed no physical activity during day 4 (+24 hours) and day 5 (+48 hours), where recovery testing was performed. Before, during, and following the 3 workouts, treatment outcomes were evaluated using blood-based muscle damage markers and hormones, perceptual measures of muscle soreness, and countermovement jump performance. RESULTS: Creatine kinase was lower for the RP treatment on day 2 (RP: 166.9 ± 56.4 vs WP: 307.1 ± 125.2 IU · L(-1), p ≤ 0.05), day 4 (RP: 232.5 ± 67.4 vs WP: 432.6 ± 223.3 IU · L(-1), p ≤ 0.05), and day 5 (RP: 176.1 ± 38.7 vs 264.5 ± 120.9 IU · L(-1), p ≤ 0.05). Interleukin-6 was lower for the RP treatment on day 4 (RP: 1.2 ± 0.2 vs WP: 1.6 ± 0.6 pg · ml(-1), p ≤ 0.05) and day 5 (RP: 1.1 ± 0.2 vs WP: 1.6 ± 0.4 pg · ml(-1), p ≤ 0.05). Muscle soreness was lower for RP treatment on day 4 (RP: 2.0 ± 0.7 vs WP: 2.8 ± 1.1 cm, p ≤ 0.05). Vertical jump power was higher for the RP treatment on day 4 (RP: 5983.2 ± 624 vs WP 5303.9 ± 641.7 W, p ≤ 0.05) and day 5 (RP: 5792.5 ± 595.4 vs WP: 5200.4 ± 501 W, p ≤ 0.05). CONCLUSIONS: Our findings suggest that during times of intense conditioning, the recovery benefits of WP are enhanced with the addition of HMB and a slow-release carbohydrate. We observed reductions in markers of muscle damage and improved athletic performance.

Developmental differences between boys and girls result in sex-specific physical fitness changes from fourth to fifth grade.

To better understand how developmental differences impact performance on a broad selection of common physical fitness measures, we examined changes in boys and girls from fourth to fifth grade. Subjects included 273 boys (age, 9.5 ± 0.6 years; height, 139.86 ± 7.52 cm; mass, 38.00 ± 9.55 kg) and 295 girls (age, 9.6 ± 0.5 years; height, 139.30 ± 7.19 cm; weight, 37.44 ± 9.35 kg). We compared anthropometrics, cardiorespiratory and local muscular endurance, flexibility, power, and strength. A mixed-method analysis of variance was used to compare boys and girls at the 2 time points. Pearson correlation coefficients were used to examine relationships between anthropometric and fitness measurements. Significance was set at p ≤ 0.05. Weight increased significantly (>10%) in both sexes, and girls became significantly taller than boys after growing 4.9% by fifth grade (vs. 3.5%). Both groups improved cardiorespiratory endurance and power, although boys performed better than girls at both time points. Boys were stronger in fourth grade, but girls improved more, leading to similar fifth-grade values. Girls were more flexible in fourth grade, but their significant decreases (∼32.4%) coupled with large improvements in boys (∼105%) resulted in similar fifth-grade scores. Body mass index (BMI) was positively correlated with run time regardless of grade or sex. Power was negatively correlated with BMI and run time in fourth grade. In conclusion, sex-specific differences in physical fitness are apparent before pubescence. Furthermore, this selection of measures reveals sexually dimorphic changes, which likely reflect the onset of puberty in girls. Coaches and teachers should account these developmental differences and their effects on anthropometrics and fitness in boys and girls.

Stripe systems with competing interactions on quasi-one dimensional periodic substrates.

We numerically examine the two-dimensional ordering of a stripe forming system of particles with competing long-range repulsion and short-range attraction in the presence of a quasi-one-dimensional corrugated substrate. As a function of increasing substrate strength or period we show that a remarkable variety of distinct orderings can be realized, including modulated stripes, prolate clump phases, two dimensional ordered kink structures, crystalline void phases, and smectic phases. Additionally in some cases the stripes align perpendicular to the substrate troughs. Our results suggest that a new route to self assembly for systems with competing interactions can be achieved through the addition of a simple periodic modulated substrate.

The relationship between muscle action and repetition maximum on the squat and bench press in men and women.

The relationship between muscle action and fatigue is not well understood, especially in terms of potential sex-specific differences. The purpose of this investigation was to determine whether a different number of repetitions could be performed on the individual muscle actions of the bench press and squat in men and women. Ten resistance-trained men (n = 10; age, 25.2 ± 1.2 years; height, 178.6 ± 8.8 cm; weight, 91.4 ± 18.1 kg; body fat, 12.7 ± 3.6%) and women (n = 10; age, 25.4 ± 2.4 years; height, 164 ± 4.0 cm; weight, 58.45 ± 3.3 kg; body fat, 20.8 ± 1.5%) participated in this balanced and randomized within-group study. Using 85% of a 1 repetition maximum, over the course of 3 visits, subjects performed 1 eccentric (ECC), concentric (CON), or combined (COMB) set to failure on the squat and bench press. Differences in muscle action and sex-specific number of repetitions to failure were compared on the squat and bench press, where significance was p ≤ 0.05. Across both exercises and sex, we observed significant differences between each of the 3 muscle actions, where the number of repetitions decreased from ECC to COMB to CON. While no sex-specific differences were observed in the squat, women performed significantly more repetitions on the ECC and CON muscle actions of the bench press. Men performed more combined repetitions, however, indicating a greater reliance on the stretch-shortening cycle. Different muscle actions contribute uniquely to the successful performance of a lift and fatigue. These contributions appear to differ in men and women.

Concurrent validity of the Armour39 heart rate monitor strap.

New technology offers potential advantages in physically demanding environments where convenience and comfort are important and accurate and reliable data collection is challenging. Nevertheless, it is important to validate the accuracy and reliability of such biological monitoring systems (BMS) before they are adopted. The purpose of this investigation was to assess the concurrent validity of a new heart rate monitor across a range of exercise intensities and with a large and diverse group of male subjects in a large cohort with diverse physical fitness characteristics. Seventy-five men (age, 23 ± 4 years; height, 181 ± 8 cm; body mass, 83 ± 12 kg; estimated V[Combining Dot Above]O2peak, 3.16 ± 0.63 [L·min]) volunteered and completed a graded cycle ergometer exercise protocol while heart rate was continuously monitored before, during, and after exercise with the new device (Armour39) and the gold standard (electrocardiogram). The 2-minute stages included sitting, standing, and cycling with 35 W increments until volitional fatigue. The coefficient of determination between mean heart rate values at each stage was R = 0.99, whereas Pearson correlations (r) at each stage were ≥ 0.99. Heart rates during exercise were typically within 1 beat of each other. The Armour39 BMS, therefore, is an acceptable means for the valid and reliable determination of heart rate under various bodily positions and levels of exertion, including maximal exercise intensity.

Feasibility Trial of a Comprehensive, Highly Patient-Centered COPD Self-Management Support Program.

Purpose: To test the feasibility of a novel self-management support intervention for people with chronic obstructive pulmonary disease (COPD). Methods: We conducted a feasibility randomized controlled trial involving patients ≥40 years with severe or very severe COPD in New York, New York (n=59). Community health workers screened patients and addressed barriers to COPD self-management. Patients were also offered home-based pulmonary rehabilitation (HBPR) and an antibiotic and steroid rescue pack. Control patients received general COPD education. Clinical outcomes for intervention and control were compared by difference-in-differences (DiD) at baseline and 6 months. The study was not powered for statistically significant differences for any measure. Feasibility measures were collected at 6 months. Results: There were high rates of completion of intervention activities, including 75% of patients undergoing evaluation for and participating in HBPR. Most (92%) intervention patients said the program was very or extremely helpful and 96% said they would participate again. Clinical outcomes generally favored the intervention: COPD assessment test, DiD -1.1 (95% confidence interval [CI] -5.9 to 3.6); 6-minute walk test distance, DiD 7.4 meters (95% CI -45.1 to 59.8); self-reported hospitalizations, DiD -9.8% (95% CI -42.3% to 22.8%); medication adherence, DiD 7.7% (-29.6%, 45.0%), and Physical Activity Adult Questionnaire, DiD 86 (95% CI -283 to 455). Intervention patients reported more emergency department visits, DiD 10.6% (95% CI 17.7% to 38.8%). Conclusions: A highly patient-centered, self-management support intervention for people with COPD was well received by patients and associated with potential improvements in clinical and self-management outcomes. A fully powered study of the intervention is warranted.

Cannabis use patterns in drug-resistant and pharmacoresponsive epilepsy: Single tertiary referral center survey investigation.

This study sought to identify differences in cannabis use and perceptions about cannabis in mitigating seizure-related symptoms in patients with epilepsy, and to evaluate differences in these patterns between drug-resistant versus pharmacoresponsive epilepsy. A collection of self-report surveys completed by patients with epilepsy (n = 76) were used to retrospectively compare differences in those with drug-resistant versus pharmacoresponsive epilepsy regarding 1) proportion who used cannabis, 2) frequency of use, 3) method of use, and 4) reason for use. A Cochran-Armitage test for trend indicated that of patients who used cannabis, a higher proportion of patients in the drug-resistant group used more frequently than in the pharmacoresponsive group. Almost half (48%) of those in the drug-resistant group reported daily use compared to approximately a third (36%) of those in the pharmacoresponsive group. Additionally, no patient in either group reported that cannabis was harmful in relation to seizure-related symptoms. Results from this study highlight the need for epilepsy providers to formally assess patients' perceptions and use of non-prescribed cannabis to inform clinical care decisions, particularly in the drug-resistant epilepsy population.

Childhood Abuse and Neglect, Exposure to Domestic Violence and Sibling Violence: Profiles and Associations With Sociodemographic Variables and Mental Health Indicators.

Research indicates substantial overlap between child abuse and neglect (CAN), exposure to domestic violence and sibling abuse, with multiple victimisation experiences conferring greater risk for adverse mental health outcomes than does exposure to a single subtype. The application of latent class analysis (LCA) to child maltreatment has gained momentum, but it remains the case that few studies have incorporated a comprehensive range of subtypes, meaning that real-life patterns in victimisation experiences cannot be accurately modelled. Based on self-report data from an ethnically diverse sample (N = 2813) of 10-17 year olds in the United Kingdom, the current study used LCA to model constellations among nine types of maltreatment in the home (physical, emotional and sexual abuse; physical and emotional neglect; exposure to physical and verbal domestic violence, or a drug-related threat; and sibling violence). A four-class solution comprising of a low victimisation class (59.3% of participants), an emotional abuse and neglect class (19.0%), a high verbal domestic violence class (10.5%) and a maltreatment and domestic violence class (11.2%) provided the best fit for the data. Associations with sociodemographic variables were examined, revealing differences in the composition of the classes. Compared to the low victimisation class, participants in the verbal domestic violence class, emotional abuse and neglect class and especially the maltreatment and domestic violence class, reported higher symptoms of anxiety and depression and an increased likelihood of non-suicidal self-injury, suicide ideation and suicide attempt. The findings carry important implications for understanding patterns of child maltreatment, and the implications for preventative strategies and support services are discussed.

Brain-Responsive Neurostimulation for the treatment of adults with epilepsy in tuberous sclerosis complex: A case series.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery. METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc). RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median reduction in disabling seizures was 58% at 1 year and 88% at last follow-up. Three of the five patients experienced some period of seizure freedom ranging from 3 months to over 1 year. SIGNIFICANCE: In this small case series, we report the first safety experience and efficacy outcomes in patients with TSC-associated drug-resistant focal epilepsy treated with direct brain-responsive neurostimulation.

Protocol for a feasibility randomized trial of self-management support for people with chronic obstructive pulmonary disease using lay health coaches.

Challenges with self-management are a major contributor to poor outcomes among adults with chronic obstructive pulmonary disease (COPD). The causes of poor self-management in COPD are manifold, and they arise from physical, cognitive, socioeconomic, environmental and societal sources. To address this complexity, we developed the Supporting self-Management Behaviors in Adults with COPD (SaMBA-COPD) model, which uses lay health coaches to identify a patient's barriers to effective COPD self-management and provide tailored support to help them overcome those barriers, reduce their symptoms and need for urgent care and improve their quality of life. The 6-month intervention includes referral of patients to a pharmacist for prescription of antibiotic and oral steroid "rescue packs" and support for a structured home exercise routine. All interactions of coaches and patients will take place by telephone or video call. We will test the feasibility and preliminary efficacy of SaMBA-COPD in a trial of 58 patients randomized 1:1 to the intervention or a COPD education control. Outcomes will be assessed at 6 and 9 months. Data from the trial will be used to inform the design of a fully powered, multi-site randomized trial of the intervention.