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JMIR Research Protocols Mar 2024Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as...
BACKGROUND
Cerebral palsy (CP) is a prevalent nonprogressive disorder that leads to impaired movement (ie, spasticity), posture, and balance, which affects functions such as walking and upper extremity tasks. Current medical treatments show efficacy in improving motor performance but have considerable side effects. Emerging off-label use of central nervous system (CNS) medications for improving motor performance has shown promising results in children with CP and other populations.
OBJECTIVE
The aim of this study is to describe a protocol for a pilot randomized controlled trial (RCT) to examine the safety, tolerability, and efficacy of methylphenidate (MPH) and modafinil on spasticity and motor performance in children with CP.
METHODS
This will be a protocol study for a pilot, triple-masked, placebo-controlled RCT (a class I trial following the American Academy of Neurology criteria) with blinded patients, outcome assessors, and intervention delivery team. Eligible children should be diagnosed with CP levels I or II based on the Gross Motor Function Classification System and be aged between 7 and 12 years. Thirty-six children with CP will be randomized into 3 groups to receive (1) MPH (2.5 mg of MPH + 100 mg placebo), (2) modafinil (100 mg modafinil + 2.5 mg placebo), or (3) a placebo (2.5 mg placebo + 100 mg placebo), in addition to physical therapy for 12 weeks. Primary outcomes include the Gross Motor Function Measure-66 and the Modified Ashworth Scale. Secondary outcomes include the Timed Up and Go test, 5 Time Sit to Stand test, Modified Clinical Test for Sensory Interaction of Balance, and 10-Meter Walk Test.
RESULTS
The protocol has been accepted by Kuwait University (VDR/EC-225) and the Ministry of Health of Kuwait (2022/2157). The inclusion of participants will start in June 2024.
CONCLUSIONS
The combination of CNS stimulant medications and controlling for rehabilitation has not been studied yet. The findings of this study may determine if using CNS stimulant medications is beneficial for the reduction of spasticity and improvement of physical function in children with spastic CP.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05675098; https://clinicaltrials.gov/study/NCT05675098.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/53728.
PubMed: 38441919
DOI: 10.2196/53728 -
Medicine Feb 2024Although patients with central disorders of hypersomnolence (CDH) exhibit characteristic symptoms of hypersomnia frequently, it takes 5 to 15 years from the onset for...
RATIONALE
Although patients with central disorders of hypersomnolence (CDH) exhibit characteristic symptoms of hypersomnia frequently, it takes 5 to 15 years from the onset for its diagnosis due to the lack of symptom recognition. Here, we present a case of idiopathic hypersomnia (IH), a CDH, wherein early diagnosis was aided by a video footage of a spontaneous sleep attack.
PATIENT CONCERNS
A 21-year-old man lost consciousness while driving and experienced an accident. He had complained of excessive daytime sleepiness (EDS) over half a year. During his hospitalization for close monitoring of the loss of consciousness, an in-room surveillance camera captured a 14-minutes long spontaneous sleep attack, during which he experienced general muscle weakness and loss of consciousness without warnings or convulsions leading to a fall from the bed. There were no abnormalities in vital signs.
DIAGNOSES
There was no significant cataplexy and less than 2 sleep-onset rapid eye movements (SOREM) in 2 sleep latency tests, with a mean sleep latency of 2.1 and 4.6 minutes. Other sleep deprivation syndromes were excluded from differential diagnosis and finally, a diagnosis of IH was confirmed according to the criteria of the Third Edition of the International Classification of Sleep Disorders. During the course of the disease, attention-deficit/hyperactive disorder (ADHD) and a gaming disorder also diagnosed.
INTERVENTIONS
Pharmacological treatment with modafinil was administered for IH and methylphenidate for ADHD. Cognitive behavioral therapy was performed for the gaming disorder.
OUTCOMES
The EDS improved, and sleep attacks were no longer observed. The disruption of daily life caused by the gaming disorder was also reduced.
LESSONS
Video recordings of sleep attacks are beneficial for identifying the cause of loss of consciousness. Home video recordings may be helpful in the early diagnosis of IH.
Topics: Humans; Male; Young Adult; Disorders of Excessive Somnolence; Idiopathic Hypersomnia; Modafinil; Sleep; Unconsciousness
PubMed: 38363934
DOI: 10.1097/MD.0000000000036782 -
Brain and Behavior Feb 2024There is media concern over students using prescription stimulants as "cognitive enhancers" to try and improve their academic performance. However, there is limited... (Review)
Review
INTRODUCTION
There is media concern over students using prescription stimulants as "cognitive enhancers" to try and improve their academic performance. However, there is limited evidence about the prevalence of this behaviour in the United Kingdom, or whether it has increased in recent years.
METHODS
We review survey studies on students' use of cognitive enhancers.
RESULTS
Overall reported use is low, with some inconclusive evidence that it is increasing. Use of modafinil appears to be higher than that of methylphenidate or dexamphetamine.
CONCLUSION
There is a clear need for large-scale research in this area, using representative sampling and survey methods that protect student anonymity.
Topics: Humans; Prevalence; Universities; Central Nervous System Stimulants; Students; Nootropic Agents; Prescriptions
PubMed: 38346719
DOI: 10.1002/brb3.3419 -
Frontiers in Physiology 2023Literature suggests pilots experience fatigue differently. So-called fatigue-resistant or -vulnerable individuals might also respond differently to countermeasures or...
Literature suggests pilots experience fatigue differently. So-called fatigue-resistant or -vulnerable individuals might also respond differently to countermeasures or stimulants. This study, which is part of a larger randomized controlled clinical trial, aims to investigate the effect of caffeine and modafinil on fatigue-resistant and -vulnerable pilots. This study included 32 healthy employees of the Royal Netherlands Air Force, who completed three test days, separated by at least 7 days. After a regular work day, the subjects were randomly administered either 300 mg caffeine, 200 mg modafinil or placebo at midnight. Hereafter the subjects performed the psychomotor vigilance test (PVT), vigilance and tracking test (VigTrack) and Stanford sleepiness scale (SSS) six times until 8 a.m. the next day. Subjects were ranked on the average number of lapses on the PVT during the placebo night and divided into three groups: fatigue-vulnerable (F), -intermediate (FINT) and -resistant (F), with 11, 10 and 11 subjects in each group, respectively. Area under the curve (AUC) of the PVT, VigTrack and SSS during the test nights were calculated, which were used in univariate factorial analysis of variance (ANOVA). Tukey's HSD tests were used to differentiate between the groups. A significant effect of treatment was found in the ANOVA of both PVT parameters, VigTrack mean reaction time and SSS. There was a statistically significant effect of fatigue group on all PVT parameters and VigTrack mean percentage omissions, where F and F scored better than F. There was a significant interaction effect between treatment and fatigue group for PVT number of lapses. This is congruent for the AUC analyses in which for all parameters (except for the SSS) the performance of the F group was consistently worse than that of the F and F groups. This study demonstrates that the performance of individuals with different fatigue tolerances are differently affected by simulants after a limited period of sleep deprivation. The classification of fatigue tolerance through PVT lapses when sleep deprived seems to be able to predict this.
PubMed: 38260091
DOI: 10.3389/fphys.2023.1303758 -
International Journal of Molecular... Jan 2024Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as...
Children with fetal alcohol spectrum disorders (FASDs) demonstrate deficits in social functioning that contribute to early withdrawal from school and delinquency, as well as the development of anxiety and depression. Dopamine is involved in reward, motivation, and social behavior. Thus, we evaluated whether neonatal ethanol exposure (in an animal model of FASDs) has an impact on social recognition memory using the three-chamber social novelty discrimination test during early and middle adolescence in male and female rats, and whether the modafinil analog, the novel atypical dopamine reuptake inhibitor CE-123, can modify this effect. Our study shows that male and female rats neonatally exposed to ethanol exhibited sex- and age-dependent deficits in social novelty discrimination in early (male) and middle (female) adolescence. These deficits were specific to the social domain and not simply due to more general deficits in learning and memory because these animals did not exhibit changes in short-term recognition memory in the novel object recognition task. Furthermore, early-adolescent male rats that were neonatally exposed to ethanol did not show changes in the anxiety index but demonstrated an increase in locomotor activity. Chronic treatment with CE-123, however, prevented the appearance of these social deficits. In the hippocampus of adolescent rats, CE-123 increased BDNF and decreased its signal transduction TrkB receptor expression level in ethanol-exposed animals during development, suggesting an increase in neuroplasticity. Thus, selective dopamine reuptake inhibitors, such as CE-123, represent interesting drug candidates for the treatment of deficits in social behavior in adolescent individuals with FASDs.
Topics: Humans; Adolescent; Child; Pregnancy; Female; Male; Animals; Rats; Social Interaction; Ethanol; Fetal Alcohol Spectrum Disorders; Dopamine Uptake Inhibitors; Dopamine; Benzhydryl Compounds
PubMed: 38256113
DOI: 10.3390/ijms25021041 -
Drug and Alcohol Dependence Feb 2024Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated...
Prediction of adverse events risk in patients with comorbid post-traumatic stress disorder and alcohol use disorder using electronic medical records by deep learning models.
BACKGROUND
Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population.
METHODS
We analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, medications, co-morbidities, individual and neighborhood level social determinants of health (SDoH), psychotherapy and veteran data.
RESULTS
DeepBiomarker2 achieved an area under the receiver operator curve (AUROC) of 0.94 on the prediction of adverse events among those PTSD+AUD patients. Medications such as vilazodone, dronabinol, tenofovir, suvorexant, modafinil, and lamivudine showed potential for risk reduction. SDoH parameters such as cognitive behavioral therapy and trauma focused psychotherapy lowered risk while active veteran status, income segregation, limited access to parks and greenery, low Gini index, limited English-speaking capacity, and younger patients increased risk.
CONCLUSIONS
Our improved version of DeepBiomarker2 demonstrated its capability of predicting multiple adverse event risk with high accuracy and identifying potential risk and beneficial factors.
Topics: Humans; Stress Disorders, Post-Traumatic; Alcoholism; Electronic Health Records; Deep Learning; Comorbidity
PubMed: 38217979
DOI: 10.1016/j.drugalcdep.2023.111066 -
Clinical Gastroenterology and... Jan 2024Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with...
Fatigue is highly prevalent in patients with IBD, affecting 72% of patients with active inflammatory bowel disease (IBD) and 47% in remission, and is associated with poor quality of life and significantly wider costs. However, understanding the mechanisms of IBD fatigue remains limited, as reflected in a lack of effective treatments..
PubMed: 38191015
DOI: 10.1016/j.cgh.2023.12.030 -
Neurology India 2023There is scarce literature on functional neuroimaging data in Kleine-Levin syndrome. The current case report presents the electrical and metabolic status of cortical...
There is scarce literature on functional neuroimaging data in Kleine-Levin syndrome. The current case report presents the electrical and metabolic status of cortical activity utilizing functional near-infrared spectroscopy (fNIRS) and quantitative electroencephalography (qEEG) before and after treatment of symptomatic phase of illness with modafinil.
Topics: Humans; Kleine-Levin Syndrome; Spectroscopy, Near-Infrared; Electroencephalography; Modafinil
PubMed: 38174469
DOI: 10.4103/0028-3886.391382 -
International Journal of Molecular... Nov 2023-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue...
-CE-123, a novel dopamine transporter inhibitor, has emerged as a potential candidate for cognitive enhancement. The objective of this study was to compare the tissue distribution profiles, with a specific focus on central nervous system distribution and metabolism, of -CE-123 and -modafinil. To address this objective, a precise liquid chromatography-high resolution mass spectrometry method was developed and partially validated. Neuropharmacokinetic parameters were assessed using the Combinatory Mapping Approach. Our findings reveal distinct differences between the two compounds. Notably, -CE-123 demonstrates a significantly superior extent of transport across the blood-brain barrier (BBB), with an unbound brain-to-plasma concentration ratio (K) of 0.5, compared to -modafinil's K of 0.1. A similar pattern was observed for the transport across the blood-spinal cord barrier. Concerning the drug transport across cellular membranes, we observed that -CE-123 primarily localizes in the brain interstitial space, whereas -modafinil distributes more evenly across both sides of the plasma membrane of the brain's parenchymal cells (K). Furthermore, our study highlights the substantial differences in hepatic metabolic stability, with -CE-123 having a 9.3-fold faster metabolism compared to -modafinil. In summary, the combination of improved BBB transport and higher affinity of -CE-123 to dopamine transporters in comparison to -modafinil makes -CE-123 a promising candidate for further testing for the treatment of cognitive decline.
Topics: Benzhydryl Compounds; Brain; Central Nervous System; Dopamine Plasma Membrane Transport Proteins; Modafinil
PubMed: 38069277
DOI: 10.3390/ijms242316956 -
Scientific Reports Nov 2023The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have... (Randomized Controlled Trial)
Randomized Controlled Trial
The use of so-called 'smart drugs' such as modafinil to improve cognitive performance has recently attracted considerable attention. However, their side effects have limited user enthusiasm. Open-label placebo (OLP) treatment, i.e., inert treatments that are openly disclosed to individuals as having no active pharmacological ingredient, has been shown to improve various medical symptoms and conditions, including those related to cognitive performance. OLP treatment could therefore be an exciting alternative to pharmacological cognitive enhancers. Here, we used a randomized-controlled design to investigate the effect of a 21-day OLP treatment on several sub-domains of cognitive performance in N = 78 healthy volunteers. Subjective and objective measures of cognitive performance as well as different measures of well-being were obtained before and after the treatment period. Using a combination of classic Frequentist and Bayesian analysis approaches showed no additional benefit from OLP treatment in any of the subjective or objective measures of cognitive performance. Our study thus highlights possible limitations of OLP treatment in boosting cognitive performance in healthy volunteers. These findings are discussed in the light of expectancy-value considerations that may determine OLP efficacy.
Topics: Humans; Attention; Bayes Theorem; Cognition; Healthy Volunteers; Modafinil; Placebo Effect
PubMed: 37945662
DOI: 10.1038/s41598-023-45979-3