Crossover Pilot Study Research Articles

Enhancing postoperative anticoagulation therapy with remote patient monitoring: A pilot crossover trial study to evaluate portable coagulometers and chatbots in cardiac surgery follow-up.

Prior research has not assessed the value of remote patient monitoring (RPM) systems for patients undergoing anticoagulation therapy after cardiac surgery. This study aims to assess whether the clinical follow-up through RPM yields comparable outcomes with the standard protocol. A crossover trial assigned participants to SOC-RPM or RPM-SOC, starting with the standard of care (SOC) for the first 6 months after surgery and using RPM for the following 6 months, or vice-versa, respectively. During RPM, patients used the Coaguchek© to accurately measure International Normalized Ratio values and a mobile text-based chatbot to report PROs and adjust the therapeutic dosage. The study assessed patients' and clinicians' experience with RPM and compared direct costs. Twenty-seven patients participated. The median time in therapeutic range (TTR) levels during RPM were 72.2% and 50.6% for the SOC-RPM and RPM-SOC arms, respectively, and during SOC, they were 49.4% and 58.4% for SOC-RPM and RPM-SOC arms, respectively. Patients and the clinical team reported high trust and satisfaction with the proposed digital service. Statistically significant differences were only found in the cost of RPM in the RPM-SOC, which was higher than SOC in the SOC-RPM arm. Portable coagulometers and chatbots can enhance the remote management of patients undergoing anticoagulation therapy, improving patient experience. This presents a promising alternative to the current standard procedure. The results of this study seem to suggest that RPM may have a higher value when initiated after a SOC period rather than starting RPM immediately after surgery.Trial registration: ClinicalTrials.gov NCT06423521.

Effect of the Location of Tetanic Stimulation on Autonomic Responses: A Randomized Cross-Over Pilot Study.

Tetanic stimuli are used as standardized noxious inputs to investigate nociception. Previous studies have applied tetanic stimuli to various anatomical locations without validating that the resulting physiological responses were independent of the location where tetanic stimuli were applied. Our aim was to investigate the effects of three anatomical tetanic stimulus application sites on physiological variables reflecting autonomic nervous system responses as measured by photoplethysmography (PPG). Under general anesthesia, a five second, 100 hertz, 70 milliamp tetanic stimulus was applied to the ulnar nerve, medial side of the tibia, and thorax (T5 dermatome) (N=12). The effect of tetanic stimuli on PPG-derived variables (AC, DC, and ACDC) and pulse rate at each stimulus location was determined using repeated-measures analysis of variance (ANOVA) followed by Dunnett's post hoc test. Maximum tetanic stimulus-induced changes in PPG-derived variables and pulse rates were compared among the three stimulus locations using ANOVA. AC and ACDC values of PPG decreased, and the DC values of PPG increased in response to tetanic stimuli-induced vasoconstriction at each location (p<0.001 for all). The maximum changes in the AC, ACDC, and DC values did not differ between locations (p=NS). There were no significant changes in pulse rate (p=NS). The results showed that tetanic stimulation at either of these three locations provides the same autonomic nervous system responses, as measured by PPG. ClinicalTrials.gov; NCT03648853.

Helping or Hindering: Inclusive Design of Automated Task Prompting for Workers with Cognitive Disabilities

Of the ∼8.8 million working-age adults with cognitive disabilities in the United States, only 28.6% are employed, contributing to a poverty rate (26.1%) for people with cognitive disabilities (PwCDs) that is more than twice that for people without disabilities. PwCDs who are employed are often still marginalized via reduced hours and pay, largely due to their more limited capability to perform work efficiently and independently. As evidence, warehouse and shelf stocking jobs that serve as employment for a significant percentage of PwCDs, often require frequent intervention from a job coach in the workplace, impacting the pay and self-esteem of these workers. This study's objective was to remove barriers to employment for PwCD through inclusive design of technology supports in warehouse and similar settings. Specifically, a nonlinear context-aware prompting system (NCAPS) was developed, iteratively refined, and tested. In a pilot crossover study, subjects with cognitive disabilities participated in simulated work sessions, picking orders in a small warehouse environment using the NCAPS and industry standard paper tickets. Their performance was assessed in terms of errors and productivity, and their insights and perspectives were gathered. The resulting NCAPS prevented or corrected all errors for all but one participant. It also increased productivity for participants with the poorest baseline (paper ticket) performance, but decreased productivity for those with high baseline performance. No significant difference was observed in system usability scale (SUS) scores between methods. Topics emerging from user input highlighted the need for technological supports for PwCD to be simple and flexible in operation, and reliable to maintain user trust. By prioritizing robustness and intuitiveness, flexible technology supports can be developed to empower workers with a broad range of abilities, including those with temporary and situational impairments. Such tools would reduce barriers to employment, including stigma, discrimination, and other barriers to equity.

Neuromodulation for Mild Cognitive Impairment: Improvements in Spatial Navigation and Associative Memory with Acute Transcutaneous Vagus Nerve Stimulation: VINCI‐AD

AbstractBackgroundNew therapeutic strategies to treat Mild Cognitive Impairment (MCI) are urgently needed. Transcutaneous Vagus Nerve Stimulation (tVNS) is a neuromodulation technique which uses a handheld device to peripherally stimulate the afferent vagus nerve. tVNS has shown promise in augmenting memory in cognitively healthy populations but data in cognitively impaired populations is sparse.MethodVINCI‐AD is an investigator‐led, single‐blind, sham‐controlled crossover pilot study assessing the effects of tVNS in amnestic MCI. All participants have MCI (CDR global 0.5) with amnestic neuropsychological profile (RBANS delayed memory index &lt;85). Participants are randomised over 3 study visits to baseline (no stimulation) active stimulation (at the CC of left ear) or sham stimulation (earlobe). Cognitive tests include Face‐Name Association Task (FNAT), Sustained Attention Response Test (SART) and Sea Hero Quest Navigation Test (SHQ) among others.ResultInterim data analysis of 28 participants is presented (mean age 71.5 (range 55‐85), 17 male, RBANS DMI 73.3 ±11.1). CSF AD biomarkers were positive for 75% (21/28) (AB‐42 460.4pg/ml (± 83.3pg/ml) and p‐tau181 82.5pg/ml [± 53.2pg/ml]) and 78% (22/28) of participants had a Charleston Comorbidity Index of ≥3. Mean tVNS stimulation time pre‐cognitive assessments was 21.2 minutes, with mean amplitude setting during active stimulation of 2.5mA (1.8‐4.5) and sham of 2.0mA (0.9‐3.1). During FNAT, active tVNS had no effect on facial recognition or reaction times, however recall accuracy was significantly improved (69.2% ±3.13) compared to baseline (44.7% ±3.51 p = 0.016) and sham (50.1% ±3.28 p = 0.021) and during active tVNS spatial navigation (38.94sec [±1.68]) was quicker than baseline (51.49sec (±3.2) p = 0.0164) and sham (51.9sec (±3.15) p = 0 .0038). We noted no significant improvements in SART or other cognitive tests performance during tVNS.ConclusiontVNS may be a useful complementary tool to augment spatial and associative memory in MCI. Further larger studies are needed to delineate precise settings in this population.

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

IntroductionHigh-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.MethodsIn 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.ResultsLarge 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.ConclusionSoft 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.

Fronto-parietal theta high-definition transcranial alternating current stimulation may modulate working memory under postural control conditions in young healthy adults.

This study aimed to investigate the immediate effects of fronto-parietal θ HD-tACS on a dual task of working memory-postural control. In this within-subject cross-over pilot study, we assessed the effects of 20 min of 6 Hz-tACS targeting both the left dorsolateral prefrontal cortex (lDLPFC) and posterior parietal cortex (PPC) in 20 healthy adults (age: 21.6 ± 1.3 years). During each session, single- and dual-task behavioral tests (working memory single-task, static tandem standing, and a dual-task of working memory-postural control) and closed-eye resting-state EEG were assessed before and immediately after stimulation. Within the tACS group, we found a 5.3% significant decrease in working memory response time under the dual-task following tACS (t = -3.157, p = 0.005, Cohen's d = 0.742); phase synchronization analysis revealed a significant increase in the phase locking value (PLV) of θ band between F3 and P3 after tACS (p = 0.010, Cohen's d = 0.637). Correlation analyses revealed a significant correlation between increased rs-EEG θ power in the F3 and P3 channels and faster reaction time (r = -0.515, p = 0.02; r = -0.483, p = 0.031, respectively) in the dual-task working memory task after tACS. However, no differences were observed on either upright postural control performance or rs-EEG results (p-values <0.05). Fronto-parietal θ HD-tACS has the potential of being a neuromodulatory tool for improving working memory performance in dual-task situations, but its effect on the modulation of concurrently performed postural control tasks requires further investigation.

Exploring the effects of resveratrol supplementation on cerebrovascular function in hormonal migraineurs: A pilot study

BackgroundPast research suggests that hormonal migraineurs may have poorer cerebrovascular function than women who do not suffer from migraine. Resveratrol, a vasoactive phytoestrogen, has been shown to improve cerebrovascular function in several populations but has never been tested in hormonal migraineurs. AimTo investigate the effects of 3-month resveratrol supplementation on the cerebrovascular function of hormonal migraineurs. MethodsWe conducted a randomised, double-blind, placebo-controlled, crossover intervention pilot study with resveratrol (150 mg/d for 3 months) in ten hormonal migraineurs (mean age: 37.2 ± 2.6 years). Participants visited the University of Newcastle’s Clinical Nutrition Research Centre where quality of life and disability, and cerebrovascular function were assessed. Quality of life and disability were examined using Migraine-Specific Quality of Life, Headache Impact Test-6 and the Migraine Disability Assessment. Cerebrovascular function was determined using transcranial Doppler ultrasound to bilaterally measure blood flow velocity in the middle and posterior cerebral arteries at rest and in response to a hypercapnic stimulus. Cerebrovascular responsiveness to a cognitive task battery was also measured bilaterally in the middle cerebral arteries. ResultsCompared to placebo, blood flow velocity in the right posterior cerebral artery was significantly higher (P = 0.041) following resveratrol supplementation. No other significant differences in cerebrovascular function between resveratrol and placebo treatments were observed. Baseline correlation analyses revealed higher blood flow velocities in the middle and posterior cerebral arteries were associated with better quality of life and less disability. However, higher cerebrovascular responsiveness to hypercapnia in the posterior circulation was associated with higher migraine-related disability and poorer migraine-related quality of life. ConclusionIn this pilot we found evidence that resveratrol may increase blood flow velocity in the right posterior cerebral artery in hormonal migraineurs. Larger cohorts are required confirm this effect and its potential relationship to migraine in premenopausal women.

TDCS over the temporal cortex to improve the functional capacity of children with cerebral palsy: Randomized, placebo-controlled, double-blind crossover pilot study

tDCS over the temporal cortex to improve the functional capacity of children with cerebral palsy: Randomized, placebo-controlled, double-blind crossover pilot study

A pilot study to investigate the efficacy and tolerability of lesion network guided transcranial electrical stimulation in outpatients with psychosis spectrum illness

BackgroundTranscranial electrical stimulation (tES) may improve psychosis symptoms, but few investigations have targeted brain regions causally linked to psychosis symptoms. We implemented a novel montage targeting the extrastriate visual cortex (eVC) previously identified by lesion network mapping in the manifestation of visual hallucinations. ObjectiveTo determine if lesion network guided High Definition-tES (HD-tES) to the eVC is safe and efficacious in reducing symptoms related to psychosis. MethodsWe conducted a single-blind crossover pilot study (NCT04870710) in patients with psychosis spectrum disorders. Participants first received HD-tDCS (direct current), followed by 4 weeks of wash out, then 2 Hz HD-tACS (alternating current). Participants received 5 days of daily (2×20 min) stimulation bilaterally to the eVC. Primary outcomes included the Positive and Negative Syndrome Scale (PANSS), biological motion task, and Event Related Potentials (ERP) from a steady state visual evoked potential (SSVEP) paradigm. Secondary outcomes included the Montgomery-Asperg Depression Rating Scale, Global Assessment of Functioning (GAF), velocity discrimination and visual working memory task, and emotional ERP. ResultsHD-tDCS improved PANSS general psychopathology in the short-term (d=0.47; pfdr=0.03), with long-term improvements in general psychopathology (d=0.62; pfdr=0.05) and GAF (d=−0.56; pfdr=0.04) with HD-tACS. HD-tDCS reduced SSVEP P1 (d=0.25; pfdr=0.005), which correlated with general psychopathology (β = 0.274, t = 3.59, p = 0.04). No significant differences in safety or tolerability measures were identified. ConclusionLesion network guided HD-tES to the eVC is a safe, efficacious, and promising approach for reducing general psychopathology via changes in neuroplasticity. These results highlight the need for larger clinical trials implementing novel targeting methodologies for the treatments of psychosis.

Safety and feasibility of transcutaneous vagus nerve stimulation in mild cognitive impairment: VINCI-AD study protocol

BackgroundOver 55 million adults are living with dementia globally, which is projected to reach 157 million by 2050. Mild cognitive impairment (MCI), a syndrome of memory impairment with intact activities of daily living, may precede dementia by several years. Around 5–15% of individuals with MCI convert to dementia annually. Novel treatments which delay progression of MCI to dementia are urgently needed. Transcutaneous vagal nerve stimulation (tVNS) is a non-invasive neuromodulation technique that targets the vagus nerve. Importantly, tVNS has been shown to improve cognition in healthy volunteers, but has not been extensively examined as a potential therapeutic approach in MCI. VINCI-AD will examine the safety and feasibility of tVNS in older adults with MCI.DesignVINCI-AD is an investigator-led, single-site, single-blind, sham-controlled crossover pilot study which aims to assess the safety and feasibility of tVNS in 40 participants with amnestic MCI. All participants will attend for three consecutive study visits during which they will be randomised to receive no stimulation (baseline), active tVNS stimulation (stimulation at cymba conchae of left ear) or sham tVNS stimulation (at earlobe). Safety will be primarily assessed by ascertainment of adverse events. Further safety assessment will examine the impact of acute tVNS on subjective (orthostatic symptoms), peripheral (finometry-based blood pressure) and central (assessed via Near Infrared Spectroscopy [NIRS]) haemodynamic responses to active stand. Feasibility will be determined using a custom-designed occupational assessment of device usability. Exploratory secondary analysis in VINCI-AD will examine the potential impact of acute tVNS on associative memory, spatial memory and inhibitory control to inform sample size estimates for future trials of tVNS in older adults with MCI.DiscussionVINCI-AD will report on the safety (adverse events/haemodynamic responses to active stand) and feasibility of tVNS as a potential therapeutic option in MCI. Detailed reporting of study eligibility and completion rates will be reported. Exploratory analysis will examine the potential cognitive benefits of acute tVNS on cognitive function in MCI to report potential effect sizes that may inform future clinical trials in this cohort.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT05514756. Trial Registration Number NCT05514756 (24th August 2022 for this protocol, version 1.0.)

Opioid receptor antagonism and neural response to monetary rewards: Pilot studies in light and heavy alcohol users.

Alcohol use disorder (AUD) is a prevalent condition associated with high degree of comorbidity and mortality. Among the few approved pharmacotherapies for AUD, two involve opioid receptor antagonism. Naltrexone and nalmefene are thought to act via opioid receptor blockage to reduce neural response to alcohol and drug-associated cues and consumption, but there have been limited efforts to characterize these effects in humans. In these studies, we sought to test the magnitude of opioid antagonism effects on neural response to monetary rewards in two groups: light drinkers (for the naltrexone study) and heavy drinkers (for the nalmefene study). We conducted double-blind, randomized, crossover pilot studies of reward activation in the brain following acute administration of opioid antagonist and placebo in 11 light and 9 heavy alcohol users. We used a monetary incentive delay task during functional MRI. We found a main effect of cue type on BOLD activation in the nucleus accumbens, demonstrating a neural reward response. The effect of opioid antagonism, relative to placebo, was small and nonsignificant for reward activation in the accumbens for both light and heavy alcohol users. Based on the results of two pilot studies, opioid antagonist medications do not appear to decrease neural activation to monetary rewards in the nucleus accumbens relative to placebo.

The influence of anthropometric parameters in track and field curve sprint.

Poor information is available regarding real field data on the different factors that could have an influence on curve sprint and its association with anthropometric and strength parameters. We designed a crossover pilot-study that enrolled 14 track and field athletes of 200 and 400 m (8/14 men, age: 20.5±2.3 years, height: 1.73±0.06 m; body mass: 60.5±6.2 kg) that performed randomly in two different days assessment of anthropometric parameters, jump test by squat jump (SJ) and triple hop distance (THD), performance during a 20-m curve sprint (day 1), and assessment of 1RM for right and left limb on Bulgarian split squat (BSS) (day 2). The unpaired t test and Pearson's correlation were used for data analysis. No statistical differences for anthropometric and strength parametric parameters between right and left lower limbs were observed. Twenty-meter curve sprints were negatively associated with body mass (P=0.0059, R=-0.7) and Body Mass Index (BMI; P=0.032, R=0.6). Moreover, a negative association was observed with SJ height (P=0.0025, R=-0.7), speed (P=0.0028; R=-0.7), strength (P=0.009, R=-0.7) and power (P=0.009, R=-0.7). Finally, 20-m curve sprint negatively correlated with right (P=0.0021, R=-0.7) and left (P<0.0001, R=-0.9) THD and 1 RM right (P=0.025, R=-0.6;) and left (P=0.0049, R=-0.7) BSS, respectively. This pilot study demonstrated that 20-m curve sprint was negatively associated with body mass, BMI, vertical jump performance, THD and 1RM BSS. This information could be useful to coaches and sport scientists as a reference value to improve athlete performance for 200- and 400-m athletes.

Desktop Virtual Reality Offers a Novel Approach to Minimize Pain and Anxiety during Burn Wound Cleaning/Debridement in Infants and Young Children: A Randomized Crossover Pilot Study.

Although most scald burn injuries involve children under six, because of the challenges of using head mounted displays with young children there is very little research exploring the use of VR in children under six. The current clinical pilot study measured the analgesic effectiveness of our new desktop VR system (with no VR helmet) in children under six during burn wound care (a within-subjects design with randomized treatment order). Between December 2021-April 2022, nine children with burn injuries (10 months to 5 years age, mean = 18 months) participated. The mean burn size was 10% Total Body Surface Area, range 2-22%. Using nurse's ratings, VR significantly reduced children's pain during burn wound care by 40% on the observational Faces, Legs, Activity, Crying, and Consolability (FLACC) pain scale. Specifically, non-parametric within-subject sign tests compared nurse's ratings of the young patients' pain during burn wound care using usual pain medications with no VR = 6.67, (SD = 2.45) vs. adjunctive Animal Rescue World VR (VR = 4.00, SD = 2.24, p < 0.01). The observational Procedure-Behavior Checklist (PBCL) nurse's scale measured a 34% reduction in anxiety with VR as compared to pharmacologic treatment alone (p < 0.005). Similarly, when using single graphic rating scales the patients' parents reported a significant 36% decrease in their child's pain during VR (p < 0.05), a 38% (p < 0.005) decrease in their child's anxiety during VR, and a significant increase in patients' joy during VR. It can be concluded that during burn wound care with no distraction (traditional pain medications), children under 6 years old experienced severe pain during a 10 min burn wound cleaning session. During burn wound care combining desktop virtual reality and traditional pain medications, the same pediatric patients experienced only mild pain during burn wound cleaning/debridement. VR significantly reduced the children's pain and anxiety during burn wound care.

A Pilot Crossover Study of Berberine and its Short-Term Effects on Blood Glucose Levels in Healthy Volunteers

Introduction: Different berberine preparations were evaluated for their effectiveness on lowering blood glucose in a pilot, open-label, crossover study conducted in healthy adults. Methods: Fourteen healthy volunteers of both sexes were recruited, and seven completed all treatments in the study. Study participants ingested one of three berberine preparations containing 500mg of berberine, respectively. A one week wash out period was included between treatments. A control group was included to measure the participants’ baseline response to a 75g glucose solution without any treatment. The following interventions were administered: berberine powder in hard gelatin capsules, berberine in an oil matrix encapsulated in soft-gelatin capsules, and berberine in LipoMicel® matrix encapsulated in soft-gelatin capsules. Blood glucose concentrations in each participant were monitored from pre-dose baseline, before the capsules were ingested, until up to 3 hours after the capsules were ingested. Results: LipoMicel Berberine treatment led to reduced blood glucose concentrations Area Under Curve (AUC, mean difference: 1.57; 95% CI: 0.021 – 3.12; P = 0.046; Cohen’s d = 1.53) and reduced maximum glucose concentration (Gmax, mean difference: 1.07; 95% CI 0.004 – 2.14; P = 0.049; Cohen’s d = 1.52) compared to the control group when no-treatment was given. No adverse events related to berberine treatments were reported by participants throughout the study period. Conclusions: LipoMicel Berberine was effective in lowering blood glucose levels by 12% after two 500mg doses. Berberine in other formulations may require a longer dosing regimen before blood glucose lowering effects can be demonstrated.

Effect of curcumin supplementation on inflammatory status and muscle damage in competitive female soccer players: a placebo-controlled, singleblind, nonrandomized, crossover pilot study.

Curcumin, a major component of turmeric, has anti-inflammatory and antioxidative properties, which are associated with protective effects against muscle damage. This study examined the effects of dietary curcumin on inflammation and muscle damage in female competitive soccer players. A single-blinded, placebo-controlled, nonrandomized, crossover pilot study was conducted. Six competitive female soccer players (20.0 ± 2.0 yearsold) who participated in a 2-week preseason training program were assigned to two conditions: placebo and curcumin. The participants ingested a placebo or curcumin dosage (270 mg/day) during 2 weeks of preseason training, with 1 week of washout. Fasting blood samples were collected under resting conditions before (day 0) and after (day 15) the training period to examine changes in the concentration of interleukin 6 (IL-6), an inflammatory marker, and indices reflective of muscle damage. Curcumin decreased the concentration of IL-6 released (mean decrease, -30.2 ± 28.1%), whereas no decrease was observed in the placebo condition (13.4 ± 17.4%). Changes in plasma IL-6 concentrations were significantly greater in the curcumin condition than in the placebo condition (p &lt; 0.05). However, curcumin supplementation had no significant effects on muscle damage indices. The present study shows that curcumin supplementation could attenuate inflammation, as indicated by IL-6 concentrations, in competitive female soccer players during the training period.

Continuous theta-burst stimulation in patients with drug-resistant epilepsy: A single-blind placebo-controlled cross-over pilot study

ObjectivesTo evaluate the effect of continuous theta-burst stimulation (cTBS) in patients with drug-resistant epilepsy (DRE). MethodsTwelve patients with DRE (five with idiopathic generalized and seven with focal epilepsy) were included in this cross-over design study and randomized to either first sham or first active stimulation, each applied for 5 consecutive days. A round coil over the vertex was used in generalized epilepsy or a figure-of-8 coil over the “epileptogenic area” in focal epilepsy. Sham stimulation was given by placing the coil 90° perpendicular to the head. The number of seizures, electroencephalography findings, Quality of Life in Epilepsy Inventory (QOLIE-84), and Symptom Check List (SCL-90) scores evaluated during the 8–12 weeks before and after active and sham stimulations were compared statistically. ResultsEight patients could complete both active and sham stimulation periods of 5 days and two patients completed active stimulation sessions, without any significant adverse effects. The number of seizures significantly reduced after active cTBS, but not after sham stimulation, when compared with those recorded before the stimulation period. QOLIE scores were increased, but interictal epileptiform discharges and SCL-90 scores showed no difference after cTBS. Active stimulation was stopped in one patient after he experienced an aggravation of myoclonic seizures. ConclusionscTBS seemed to be relatively safe and gave promising results in reducing the frequency of seizures in patients with both generalized and focal DRE. This time-saving technique may ease the introduction of repetitive transcranial magnetic stimulation into the routine practice of busy epilepsy clinics.

Effectiveness of Shiatsu on Fatigue in Patients with Axial Spondyloarthritis: Protocol for a Randomized Cross-Over Pilot Study.

Spondyloarthritis (SpA) is a serious chronic inflammatory rheumatism implying different painful and crippling symptoms that require a multidisciplinary approach for the patient. Fatigue is one of the less well treated symptoms, even if its repercussion on everyday life is noticeable. Shiatsu is a Japanese preventive and well-being therapy that aims to promote better health. However, the effectiveness of shiatsu in SpA-associated fatigue has never been studied yet in a randomized study. We describe the design of SFASPA (Etude pilote randomisée en cross-over évaluant l'efficacité du Shiatsu sur la FAtigue des patients atteints de SPondyloarthrite Axiale), a single-center, randomized controlled cross-over trial with allocation of patients according to a ratio (1:1) evaluating the effectiveness of shiatsu in SpA-associated fatigue. The sponsor is the Regional Hospital of Orleans, France. The two groups of 60 patients each will receive three "active" shiatsu and three sham shiatsu treatments (120 patients, 720 shiatsu). The wash-out period between the active and the sham shiatsu treatments is 4months. The primary outcome is the percentage of patients responding to the FACIT-fatigue score. A response to fatigue is defined as an improvement, i.e., an increase of ≥ 4 points in the FACIT-fatigue score, which corresponds to the "minimum clinically important difference" (MCID). Differences in the evolution of activity and impact of the SpA will be assessed on several secondary outcomes. An important aim of this study is also to gather material for further trials with higher proof of evidence. NCT05433168, date of registration, June 21st, 2022 (clinicaltrials.gov).

Influence of Transcranial Direct Current Stimulation and Exercise on Physical Capacity and Gait in Multiple Sclerosis: A Cross-Over Pilot Study.

Physical capacity provides a link between disease or impairment and limitations in activity; in multiple sclerosis (MS), it is limited and decreased. The aim of this study was to study the effects of exercise and transcranial direct current stimulation (tDCS) on the left dorsolateral prefrontal cortex area in MS patients with fatigue and an impaired gait ability. A cross-over design was carried out on fifteen patients with two disability associations, but three were excluded. Before and after each intervention, the 6 min walk test (6MWT) and the 2 min walk test (2MWT) were used to assess walking ability and the Modified Fatigue Impact Scale (MFIS) was used to assess fatigue. A total of twelve patients were enrolled (48.0 median age, Kurtzke Disability Scale (EDSS) 3.66 ± 1.3): five females and seven males. After the application of the exercise program, significant improvements were observed in the 6MWT (p < 0.001, g = 0.159) and 2MWT (p < 0.001, g = 0.182). Furthermore, fatigue was significantly reduced after the application of the exercise program (p < 0.05, g = 0.742) and after tDCS (p < 0.05, g = 0.525). We could consider therapeutic exercise in the future to improve the walking ability and fatigue in MS patients. Furthermore, tDCS did not exert a significant improvement in walking ability, but it appeared to influence fatigue. Clinical trial registration code: ACTRN12622000264785.

Measuring Oxygenation in Newborn Infants with Targeted Oxygen Ranges (MONITOR): a randomised crossover pilot study

ObjectiveThe Neonatal Oxygenation Prospective Meta-analysis (NeOProM) Collaboration showed that high (91–95%) versus low (85–89%) SpO2 targets reduced mortality. Trials of higher targets are needed to determine whether any more survival...

Detections of organophosphate and pyrethroid insecticide metabolites in urine and sweat obtained from women during infrared sauna and exercise: A pilot crossover study.

Synthetic pesticides such as organophosphates and pyrethroids are commonly used worldwide yet the metabolic and long-term human health effects of these environmental exposures are unclear. Urinary detections of metabolites involving both classes of insecticides have been documented in various global populations. However, reports documenting similar detections in human sweat are sparse. In this study, the concentrations of four insecticide metabolites were measured using liquid chromatography coupled with tandem mass spectrometry in repeated sweat and urine collections (n=85) from 10 women undergoing three interventions (control, infrared sauna and indoor bicycling) within a single-blinded randomised crossover trial. The Friedman test with post-hoc two-way analysis of variance, the related-samples Wilcoxon signed rank test and the Spearman's rank-order correlation test were used to analyse the results. Organophosphate metabolites were detected in 84.6% (22/26) and pyrethroids in 26.9% (7/26) of the collected sweat samples (pooled per individual, per intervention). Urinary concentrations of three of the four metabolites marginally increased after infrared sauna bathing: 3,5,6-trichloro-2-pyridinol (z=2.395, p=0.017); 3-phenoxybenzoic acid (z=2.599, p=0.009); and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (z=2.090, p=0.037). Urinary 3-phenoxybenzoic acid also increased after exercise (z=2.073, p=0.038) and demonstrated the most temporal variability (days to weeks) of any of the urinary metabolites. Definitive sweat/urine correlations were not demonstrated. These results indicate metabolites from organophosphate and pyrethroid pesticides can be detected in human sweat and this raises intriguing questions about perspiration and its role in the metabolism and excretion of synthetic pesticides.