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1.
J Sleep Res ; : e14045, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37720977

RESUMO

Excessive daytime sleepiness is the core symptom of central disorders of hypersomnolence (CDH) and can directly impair driving performance. Sleepiness is reflected in relative alterations in distal and proximal skin temperature. Therefore, we examined the predictive value of skin temperature on driving performance. Distal and proximal skin temperature and their gradient (DPG) were continuously measured in 44 participants with narcolepsy type 1, narcolepsy type 2 or idiopathic hypersomnia during a standardised 1-h driving test. Driving performance was defined as the standard deviation of lateral position (SDLP) per 5 km segment (equivalent to 3 min of driving). Distal and proximal skin temperature and DPG measurements were averaged over each segment and changes over segments were calculated. Mixed-effect model analyses showed a strong, quadratic association between proximal skin temperature and SDLP (p < 0.001) and a linear association between DPG and SDLP (p < 0.021). Proximal skin temperature changes over 3 to 15 min were predictive for SDLP. Moreover, SDLP increased over time (0.34 cm/segment, p < 0.001) and was higher in men than in women (3.50 cm, p = 0.012). We conclude that proximal skin temperature is a promising predictor for real-time assessment of driving performance in people with CDH.

2.
Hum Psychopharmacol ; 38(1): e2858, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36420633

RESUMO

OBJECTIVE: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving performance in participants with narcolepsy. METHODS: In this randomised, double-blind, placebo-controlled, crossover study, driving performance during a 1 h on-road driving test was assessed at 2 and 6 h post-dose following 7 days of treatment with solriamfetol (150 mg/day for 3 days, followed by 300 mg/day for 4 days) or placebo. The primary endpoint was standard deviation of lateral position (SDLP) at 2 h post-dose. RESULTS: The study included 24 participants (54% male; mean age, 40 years); 22 had evaluable SDLP data. At 2 h post-dose, median SDLP was significantly lower (improved) with solriamfetol compared with placebo (19.08 vs. 20.46 cm [median difference, -1.9 cm], p = 0.002). Four participants on solriamfetol and 7 on placebo had incomplete driving tests. At 6 h post-dose, median SDLP was not statistically significantly different with solriamfetol compared with placebo (19.59 vs. 19.78 cm [median difference, -1.1 cm], p = 0.125). Three participants on solriamfetol and 10 on placebo had incomplete driving tests. Common adverse events (≥5%) included headache, decreased appetite, and somnolence. CONCLUSIONS: Solriamfetol 300 mg/day improved on-the-road driving performance, at 2 h post-administration in participants with narcolepsy.


Assuntos
Condução de Veículo , Narcolepsia , Humanos , Masculino , Adulto , Feminino , Estudos Cross-Over , Narcolepsia/tratamento farmacológico , Carbamatos/efeitos adversos , Fenilalanina/uso terapêutico , Método Duplo-Cego
3.
Neurol Ther ; 12(1): 249-265, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36494591

RESUMO

INTRODUCTION: Excessive daytime sleepiness (EDS) associated with narcolepsy or obstructive sleep apnea (OSA) can impair vigilance/attention. Solriamfetol, a dopamine/norepinephrine reuptake inhibitor, is approved to treat EDS associated with narcolepsy (75-150 mg/day) or OSA (37.5-150 mg/day). The analysis reported here explored the use of the Sleep, Activity, Fatigue, and Task Effectiveness (SAFTE) model (used in transport industries to model performance based on accumulated sleep and circadian variability) as a substitute for healthy controls using psychomotor vigilance task (PVT) data collected during clinical studies. METHODS: Data were analyzed from two phase 2 studies of solriamfetol in adults with OSA (NCT02806895, EudraCT 2015-003930-28) or narcolepsy (NCT02806908, EudraCT 2015-003931-36). Participants were randomly assigned 1:1 to solriamfetol 150 mg/day (3 days) followed by 300 mg/day (4 days), or placebo (7 days), then crossed over to the other treatment. Actual task effectiveness scores were calculated from average PVT inverse reaction time (pre-dose; 2 h post-dose; 6 h post-dose). Actigraphy-derived sleep intervals were used in SAFTE to determine modeled healthy control task effectiveness scores. RESULTS: In participants with OSA (N = 31) on placebo or solriamfetol, actual and modeled healthy control task effectiveness did not differ at any time point. In participants with narcolepsy (N = 20) on placebo, actual task effectiveness at 2 h post-dose was lower than modeled healthy control task effectiveness (nominal P = 0.03), a difference not present with solriamfetol. There was no main effect of solriamfetol on actual or modeled healthy control task effectiveness across time points. CONCLUSION: This study represents a novel application of the SAFTE biomathematical model to approximate healthy controls in sleep disorder research and provides valuable lessons that may optimize future research. Future studies should perform a priori power analyses for model-tested outcomes and use sleep measures that capture sleep fragmentation characteristic of sleep disorders for sleep input (e.g., total sleep time rather than time in bed). TRIAL REGISTRATION: NCT02806895, EudraCT 2015-003930-28: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Obstructive Sleep Apnea. NCT02806908, EudraCT 2015-003931-36: A Randomized, Double-Blind, Placebo-Controlled, Crossover On-Road Driving Study Assessing the Effect of JZP-110 on Driving Performance in Subjects With Excessive Sleepiness Due to Narcolepsy.

4.
Disabil Rehabil ; 45(2): 244-251, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35107392

RESUMO

PURPOSE: This exploratory case-controlled study examined whether the same amount of effort leads to similar feelings of fatigue and whether feelings of fatigue decline at the same rate in people with traumatic brain injury (pwTBI) compared to controls. METHODS: Twenty pwTBI and 20 healthy controls (HC) completed an adaptive n-back task to induce fatigue and reported mental effort upon task completion and state-fatigue pre-task and several times during 30-minutes rest-period post-task. Task difficulty adapted to performance allowing both groups to invest substantial amounts of mental effort. RESULTS: Fatigue and effort levels were higher in pwTBI compared to controls. Multiple linear regression analyses showed that effort was positively related to post-task fatigue and this relationship did not differ between groups. Pre-task fatigue was the only predictor of post-task fatigue. Multilevel models showed no significant difference in decline of fatigue over the rest-period between groups. CONCLUSIONS: Excessive feelings of fatigue following TBI could not be explained by a higher vulnerability to the fatigue-inducing effects of mental effort needed to perform a specific task. In pwTBI pre-task fatigue levels might be more related to the complex demands of everyday life. Future studies should investigate recovery of fatigue and applications of this knowledge to rehabilitation interventions.Implications for rehabilitationPeople with TBI experience long-term fatigue as one of the most frequent and disabling symptoms and this long-term fatigue is a risk factor for development of secondary psychiatric symptoms such as depression or anxiety.Since people with TBI did not show a higher vulnerability to the fatigue-inducing effects of mental effort, fatigue following TBI might be better explained by the complex demands of everyday life such as external (environment) and internal (emotions) factors.Rehabilitation programs should be directed to this complex and highly individual interplay of fatigue in relation to other factors.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/complicações , Fadiga/diagnóstico , Emoções , Transtornos de Ansiedade , Estudos de Casos e Controles
5.
Hum Psychopharmacol ; 37(6): e2845, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35633275

RESUMO

OBJECTIVE: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnoea (OSA). METHODS: Eligible participants were aged 21-75 years with OSA and EDS (Maintenance of Wakefulness Test mean sleep latency <30 minutes and Epworth Sleepiness Scale score ≥10). Participants were randomised 1:1 to solriamfetol (150 mg/day [3 days], then 300 mg/day [4 days]) or placebo for 7 days, before crossover to the other treatment paradigm. On Day 7 of each period, standardised on-road driving tests occurred (2 and 6 hours postdose). Standard deviation of lateral position (SDLP) was the primary endpoint. RESULTS: Solriamfetol significantly reduced SDLP at 2 (n = 34; least squares mean difference, -1.1 cm; 95% CI, -1.85, -0.32; p = 0.006) and 6 hours postdose (n = 32; least squares mean difference, -0.8 cm; 95% CI, -1.58, -0.03; p = 0.043). Two hours postdose, 4 placebo-treated and 1 solriamfetol-treated participants had incomplete driving tests; 6 hours postdose, 7 and 3 participants, respectively, had incomplete tests. Common treatment-emergent adverse events included headache, nausea, and insomnia. CONCLUSIONS: Solriamfetol 300 mg/day significantly improved on-the-road driving performance in participants with EDS associated with OSA.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Apneia Obstrutiva do Sono , Humanos , Distúrbios do Sono por Sonolência Excessiva/etiologia , Distúrbios do Sono por Sonolência Excessiva/complicações , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/tratamento farmacológico , Carbamatos/efeitos adversos , Fenilalanina/uso terapêutico
6.
J Sleep Res ; 31(3): e13518, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34755413

RESUMO

Patients with narcolepsy or idiopathic hypersomnia (IH) are at increased risk of driving accidents. Both excessive daytime sleepiness, i.e. unwanted sleep episodes during the day, and disturbed vigilance are core features of these disorders. We tested on-the-road driving performance of patients with narcolepsy or IH coming in for a routine driving fitness evaluation and examined: (1) correlations between driving performance and the Maintenance of Wakefulness Test (MWT), Sustained Attention to Response Task (SART) and Psychomotor Vigilance Test (PVT) as objective tests; (2) the predictive power of the MWT and SART for increased risk of impaired driving; (3) the best set of objective predictors for increased risk of impaired driving. Participants were 44 patients (aged 18-75 years) with narcolepsy type 1 (NT1), type 2 (NT2) or IH. They completed the MWT, SART, PVT, a subjective sleepiness questionnaire, and a standardised on-the-road driving test. The standard deviation of the lateral position (SDLP) was used as outcome measure of driving performance. The MWT had low correlation with the SDLP (ρ = -0.41 to -0.49, p < 0.01). The SART and PVT had low correlations with SDLP (ρ = 0.30 and ρ = 0.39, respectively, both p < 0.05). The predictive power of MWT for an increased risk of impaired driving was significant, but low (area under the curve = 0.273, p = 0.012), and non-significant for SART. We conclude that in our present group, none of the tests had adequate ability to predict impaired driving, questioning their use for clinical driving fitness evaluation in narcolepsy and IH. Real-time monitoring of sleepiness while driving seems more promising in these patients.


Assuntos
Distúrbios do Sono por Sonolência Excessiva , Hipersonia Idiopática , Narcolepsia , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Humanos , Hipersonia Idiopática/diagnóstico , Narcolepsia/diagnóstico , Sonolência , Inquéritos e Questionários , Vigília/fisiologia
7.
J Sleep Res ; 30(5): e13334, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33719114

RESUMO

Sleep and physical activity are both modifiable behavioural factors that are associated with better health and are potentially related. Following traumatic brain injury, damage to the brain caused by an external force, sleep disturbances are common. Exploring bidirectional relationships between sleep and physical activity might provide insight into whether increasing physical activity could decrease these sleep disturbances. The current study, therefore, examined inter- and intra-individual temporal associations between sleep and daytime physical activity in 64 people with traumatic brain injury reporting sleep problems or fatigue (47 males; mean age, 40 years). Sleep and physical activity were measured using actigraphy with corroborating sleep diaries over 14 consecutive days. Multilevel models were used to examine inter- and intra-individual associations between physical activity and sleep. Inter-individual variations showed that earlier bedtimes, earlier wake-up times and lower sleep efficiency were associated with more physical activity. Intra-individual temporal variations showed no significant association of daytime physical activity with sleep duration or continuity. However, shorter sleep time and less wake after sleep onset than usual were associated with more time spent in light-intensity activity the next day. Therefore, sleep may have more of an influence on physical activity than physical activity has on sleep in people with traumatic brain injury. In conclusion, the results do not confirm a potential beneficial effect of physical activity on sleep but suggest that improving sleep quality might be relevant to support of a physically active lifestyle in people with traumatic brain injury. Further research is necessary to confirm these results.


Assuntos
Lesões Encefálicas Traumáticas , Sono , Actigrafia , Adulto , Lesões Encefálicas Traumáticas/complicações , Exercício Físico , Humanos , Masculino , Polissonografia
8.
Hum Psychopharmacol ; 36(4): e2778, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33547849

RESUMO

OBJECTIVE: Previous research reported cognitive and psychomotor impairments in long-term users of benzodiazepine receptor agonists (BZRAs). This article explores the role of acute intoxication and clinical complaints. METHODS: Neurocognitive and on-road driving performance of 19 long-term (≥6 months) regular (≥twice weekly) BZRA users with estimated plasma concentrations, based on self-reported use, exceeding the therapeutic threshold (CBZRA +), and 31 long-term regular BZRA users below (CBZRA -), was compared to that of 76 controls. RESULTS: BZRA users performed worse on tasks of response speed, processing speed, and sustained attention. Age, but not CBZRA or self-reported clinical complaints, was a significant covariate. Road-tracking performance was explained by CBZRA only. The CBZRA  + group exhibited increased mean standard deviation of lateral position comparable to that at blood-alcohol concentrations of 0.5 g/L. CONCLUSIONS: Functional impairments in long-term BZRA users are not attributable to self-reported clinical complaints or estimated BZRA concentrations, except for road-tracking, which was impaired in CBZRA + users. Limitations to address are the lack of assessment of objective clinical complaints, acute task related stress, and actual BZRA plasma concentrations. In conclusion, the results confirm previous findings that demonstrate inferior performance across several psychomotor and neurocognitive domains in long-term BZRA users.


Assuntos
Condução de Veículo , Benzodiazepinas , Concentração Alcoólica no Sangue , Humanos , Individualidade , Desempenho Psicomotor , Tempo de Reação , Receptores de GABA-A
9.
Psychopharmacology (Berl) ; 238(1): 83-94, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32939597

RESUMO

RATIONALE: The mechanisms underlying impaired sleep quality in insomnia are not fully known, but an important role for sleep fragmentation has been proposed. OBJECTIVES: The aim of this study is to explore potential mechanisms of sleep fragmentation influencing alterations of perceived sleep quality. METHODS: We analyzed polysomnography (PSG) recordings from a double-blind crossover study with zopiclone 7.5 mg and placebo, in elderly participants with insomnia complaints and age-matched healthy controls. We compared survival dynamics of sleep and wake across group and treatment. Subsequently, we used a previously proposed model to estimate the amount of sleep onset latency (SOL) misperception from PSG-defined sleep fragmentation. Self-reported and model-estimated amount of SOL misperception were compared across group and treatment, as well as model prediction errors. RESULTS: In the zopiclone night, the average segment length of NREM sleep was increased (group F = 1.16, p = 0.32; treatment F = 8.89, p < 0.01; group x treatment F = 0.44, p = 0.65), while the segment length of wake was decreased (group F = 1.48, p = 0.23; treatment F = 11.49, p < 0.01; group x treatment F = 0.36, p = 0.70). The self-reported and model-estimated amount of SOL misperception were lower during the zopiclone night (self-reported group F = 6.08, p < 0.01, treatment F = 10.8, p < 0.01, group x treatment F = 2.49, p = 0.09; model-estimated F = 1.70, p = 0.19, treatment F = 16.1, p < 0.001, group x treatment F = 0.60, p = 0.55). The prediction error was not altered (group F = 1.62, p = 0.20; treatment F = 0.20, p = 0.65; group x treatment F = 1.01, p = 0.37). CONCLUSIONS: Impaired subjective sleep quality is associated with decreased NREM stability, together with increased stability of wake. Furthermore, we conclude that zopiclone-induced changes in SOL misperception can be largely attributed to predictable changes of sleep architecture.


Assuntos
Compostos Azabicíclicos/uso terapêutico , Piperazinas/uso terapêutico , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Sono REM/efeitos dos fármacos , Adulto , Idoso , Compostos Azabicíclicos/administração & dosagem , Ensaios Clínicos como Assunto , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperazinas/administração & dosagem , Polissonografia , Autorrelato , Privação do Sono/prevenção & controle
11.
Hum Psychopharmacol ; 36(1): 1-12, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001492

RESUMO

OBJECTIVE: To assess driving performance and neurocognitive skills of long-term users of sedating antidepressants, in comparison to healthy controls. METHODS: Thirty-eight long-term (>6 months) users of amitriptyline (n = 13) and mirtazapine (n = 25) were compared to 65 healthy controls. Driving performance was assessed using a 1-h standardised highway driving test in actual traffic, with road-tracking error (standard deviation of lateral position [SDLP]) being the primary measure. Secondary measures included neurocognitive tasks related to driving. Performance differences between groups were compared to those of blood alcohol concentrations of 0.5 mg/ml to determine clinical relevance. RESULTS: Compared to controls, mean increase in SDLP of all antidepressant users was not significant, nor clinically relevant (+0.75 cm, 95% CI: -0.83 cm; +2.33 cm). However, users treated less than 3 years (n = 20) did show a significant and clinically relevant increase in SDLP (+2.05 cm). No significant effects were observed on neurocognitive tasks for any user group, although large individual differences were present. Most results from neurocognitive tests were inconclusive, while a few parameters confirmed non-inferiority for users treated longer than 3 years. CONCLUSION: The impairing effects of antidepressant treatment on driving performance and neurocognition mitigate over time following long-term use of 3 years.


Assuntos
Antidepressivos/efeitos adversos , Condução de Veículo , Hipnóticos e Sedativos/efeitos adversos , Desempenho Psicomotor/efeitos dos fármacos , Condução de Veículo/psicologia , Concentração Alcoólica no Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
J Rehabil Med ; 52(11): jrm00129, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33205217

RESUMO

OBJECTIVE: To evaluate the construct validity of Psychomotor Vigilance Test performance for measuring fatigue in people with acquired brain injury. DESIGN: Observational cross-sectional study. PARTICIPANTS: Fifty-four people with acquired brain injury and 61 healthy controls. METHODS: Participants performed the Psychomotor Vigilance Test and reported momentary fatigue before and after this test and general fatigue. Associations between performance and fatigue in patients were tested by correlational and hierarchical multiple linear regression analyses, controlling for sleep quality, daytime sleepiness, and mood. RESULTS: Patients performed worse on the test compared with controls. Within the patient group, worse test performance was associated with increases in momentary post-test fatigue and general fatigue, indicating convergent validity, but also with daytime sleepiness, and mood complaints, indicating a lack of divergent validity. When controlling for sleepiness and mood, the association between performance and general fatigue was no longer significant, whereas the association between performance and post-test fatigue remained. CONCLUSION: Performance on the Psychomotor Vigilance Test cannot be used as a specific measure for fatigue, but it appears to be a more general measure of severity of symptoms including fatigue, mood, and sleepiness. Therefore, the Psychomotor Vigilance Test may be a useful measure to examine the effects of interventions aimed at reducing these symptoms.


Assuntos
Lesões Encefálicas/complicações , Fadiga/diagnóstico , Desempenho Psicomotor/fisiologia , Adulto , Idoso , Lesões Encefálicas/patologia , Estudos de Casos e Controles , Estudos Transversais , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Hum Psychopharmacol ; 34(6): e2715, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31837049

RESUMO

OBJECTIVE: The aim of this study is to compare actual driving performance and skills related to driving of patients using benzodiazepine anxiolytics or hypnotics for at least 6 months to that of healthy controls. METHODS: Participants were 44 long-term users of benzodiazepine and benzodiazepine-related anxiolytics (n = 12) and hypnotics (n = 32) and 65 matched healthy controls. Performance was assessed using an on-the-road driving test measuring standard deviation of lateral position (SDLP, in cm) and a battery of neurocognitive tasks. Performance differences between groups were compared with a blood alcohol concentration of 0.5 mg/ml to determine clinical relevance. RESULTS: Compared with controls, SDLP was significantly increased in hypnotic users (+1.70 cm) but not in anxiolytic users (+1.48 cm). Anxiolytic and hypnotic users showed significant and clinically relevant impairment on neurocognitive task measuring executive functioning, vigilance, and reaction time. For patients using hypnotics for at least 3 years, no significant driving impairment was observed. CONCLUSION: Impairing effects of benzodiazepine hypnotics on driving performance may mitigate over time following longer term use (i.e. 3 years or more) although neurocognitive impairments may remain.


Assuntos
Condução de Veículo/psicologia , Benzodiazepinas/efeitos adversos , Cognição/efeitos dos fármacos , Usuários de Drogas/psicologia , Voluntários Saudáveis/psicologia , Ansiolíticos/efeitos adversos , Concentração Alcoólica no Sangue , Estudos de Casos e Controles , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Testes Psicológicos , Fatores de Tempo
15.
J Alzheimers Dis ; 69(4): 1019-1030, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31045516

RESUMO

BACKGROUND/OBJECTIVE: Neurodegenerative disorders impact fitness to drive of older drivers, but on-road driving studies investigating patients with different neurodegenerative disorders are scarce. A variety of driving errors have been reported in patients with Alzheimer's disease (AD), but it is unclear which types of driving errors occur most frequently. Moreover, patients with other neurodegenerative disorders than AD typically present with different symptoms and impairments, therefore different driving errors may be expected. METHODS: Patients with AD (n = 80), patients with other neurodegenerative disorders with cognitive decline (i.e., vascular dementia, frontotemporal dementia, dementia with Lewy bodies/Parkinson's disease, n = 59), and healthy older drivers (n = 45) participated in a fitness-to-drive assessment study including on-road driving. RESULTS: Patients with AD performed significantly worse than healthy older drivers on operational, tactical, visual, and global aspects of on-road driving. In patients with AD, on-road measures were significantly associated with 'off-road' measures. Patients with neurodegenerative disorders other than AD showed large overlap in the types of driving errors. Several driving errors were identified that appear to be characteristic for patients with particular neurodegenerative disorders. CONCLUSION: Patients from each group of neurodegenerative disorders commonly display tactical driving errors regarding lane positioning, slow driving, observation of the blind spot, and scanning behavior. Several other tactical and operational driving errors, including not communicating with cyclists and unsteady steering, were more frequently observed in patients with non-AD neurodegenerative disorders. These findings have implications for on-road and 'off-road' fitness-to-drive assessments for patients with neurodegenerative disorders with cognitive decline.


Assuntos
Doença de Alzheimer/psicologia , Condução de Veículo/psicologia , Doenças Neurodegenerativas/psicologia , Idoso , Idoso de 80 Anos ou mais , Exame para Habilitação de Motoristas/psicologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino
16.
Sleep Med ; 57: 70-79, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30897458

RESUMO

STUDY OBJECTIVE: To study sleep EEG characteristics associated with misperception of Sleep Onset Latency (SOL). METHODS: Data analysis was based on secondary analysis of standard in-lab polysomnographic recordings in 20 elderly people with insomnia and 21 elderly good sleepers. Parameters indicating sleep fragmentation, such as number of awakenings, wake after sleep onset (WASO) and percentage of NREM1 were extracted from the polsysomnogram, as well as spectral power, microarousals and sleep spindle index. The correlation between these parameters during the first sleep cycle and the amount of misperceived sleep was assessed in the insomnia group. Additionally, we made a model of the minimum duration that a sleep fragment at sleep onset should have in order to be perceived as sleep, and we fitted this model to subjective SOLs of both subject groups. RESULTS: Misperception of SOL was associated with increased percentage of NREM1 and more WASO during sleep cycle 1. For insomnia subjects, the best fit of modelled SOL with subjective SOL was found when assuming that sleep fragments shorter than 30 min at sleep onset were perceived as wake. The model indicated that healthy subjects are less sensitive to sleep interruptions and perceive fragments of 10 min or longer as sleep. CONCLUSIONS: Our findings suggest that sleep onset misperception is related to sleep fragmentation at the beginning of the night. Moreover, we show that people with insomnia needed a longer duration of continuous sleep for the perception as such compared to controls. Further expanding the model could provide more detailed information about the underlying mechanisms of sleep misperception.


Assuntos
Eletroencefalografia/instrumentação , Privação do Sono/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Latência do Sono , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Sono REM/fisiologia
17.
Sleep ; 42(4)2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30597112

RESUMO

STUDY OBJECTIVES: To assess potential effects of lemborexant on next-morning driving performance in adult and elderly healthy volunteers. METHODS: Randomized, double-blind, double-dummy, placebo and active-controlled, four period incomplete crossover study in 48 healthy volunteers (22 females), 23-78 years old. Participants were treated at bedtime for eight consecutive nights with two of three dose levels of lemborexant (2.5, 5, or 10 mg), zopiclone 7.5 mg (on the first and last night with placebo on intervening nights), or placebo. Driving performance was assessed in the morning on days 2 and 9 using a standardized highway driving test in normal traffic, measuring standard deviation of lateral position (SDLP). Drug-placebo differences in SDLP >2.4 cm were considered to reflect clinically meaningful driving impairment. RESULTS: Mean drug-placebo differences in SDLP following lemborexant 2.5, 5, and 10 mg on days 2 and 9 were 0.74 cm or less. The upper bound of the 95% confidence intervals (CIs) for lemborexant treatment groups were all below 2.4 cm and the 95% CIs included zero, indicating that the effects were neither clinically meaningful nor statistically significant. Symmetry analysis further supported the lack of clinically meaningful impairment with lemborexant. CONCLUSIONS: When assessed starting ~9 h after lemborexant administration at bedtime the previous night, there was no statistically significant or clinically meaningful effect on driving performance in healthy adults and elderly, as assessed by either mean differences in SDLP relative to placebo or symmetry analysis. In this study, lemborexant at doses up to 10 mg was well-tolerated. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, NCT02583451. https://clinicaltrials.gov/ct2/show/NCT02583451.


Assuntos
Compostos Azabicíclicos/farmacologia , Dirigir sob a Influência/estatística & dados numéricos , Hipnóticos e Sedativos/farmacologia , Antagonistas dos Receptores de Orexina/farmacologia , Piperazinas/farmacologia , Desempenho Psicomotor/efeitos dos fármacos , Piridinas/farmacologia , Pirimidinas/farmacologia , Adulto , Idoso , Condução de Veículo , Estudos Cross-Over , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
JMIR Res Protoc ; 7(10): e11295, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30348629

RESUMO

BACKGROUND: Fatigue and sleep problems are common after a traumatic brain injury (TBI) and are experienced as highly distressing symptoms, playing a significant role in the recovery trajectory, and they can drastically impact the quality of life and societal participation of the patient and their family and friends. However, the etiology and development of these symptoms are still uncertain. OBJECTIVE: The aim of this study is to examine the development of fatigue and sleep problems following moderate to severe TBI and to explore the changes in underlying biological (pain, brain damage), psychological (emotional state), and social (support family, participation) factors across time. METHODS: This study is a longitudinal multicenter observational cohort study with 4 measurement points (3, 6, 12, and 18 months postinjury) including subjective questionnaires and cognitive tasks, preceded by 7 nights of actigraphy combined with a sleep diary. Recruitment of 137 moderate to severe TBI patients presenting at emergency and neurology departments or rehabilitation centers across the Netherlands is anticipated. The evolution of fatigue and sleep problems following TBI and their association with possible underlying biological (pain, brain damage), psychological (emotional state), and social (support family, participation) factors will be examined. RESULTS: Recruitment of participants for this longitudinal cohort study started in October 2017, and the enrollment of participants is ongoing. The first results are expected at the end of 2020. CONCLUSIONS: To the authors' knowledge, this is the first study that examines the development of both post-TBI fatigue and sleep longitudinally within a biopsychosocial model in moderate to severe TBI using both subjective and objective measures. Identification of modifiable factors such as mood and psychosocial stressors may give direction to the development of interventions for fatigue and sleep problems post-TBI. TRIAL REGISTRATION: Netherlands Trial Register NTR7162; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=7162 (Archived by WebCite at http://www.webcitation.org/6z3mvNLuy). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/11295.

19.
Alzheimer Dis Assoc Disord ; 32(1): 70-75, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29189301

RESUMO

Dementia is a risk factor for unsafe driving. Therefore, an assessment strategy has recently been developed for the prediction of fitness to drive in patients with the Alzheimer disease (AD). The aim of this study was to investigate whether this strategy is also predictive of fitness to drive in patients with non-AD dementia, that is, vascular dementia, frontotemporal dementia, and dementia with Lewy bodies. Predictors were derived from 3 types of assessment: clinical interviews, neuropsychological tests, and driving simulator rides. The criterion was the pass-fail outcome of an official on-road driving assessment. About half of the patients with non-AD dementia (n=34) failed the on-road driving assessment. Neuropsychological assessment [area under the curve (AUC)=0.786] was significantly predictive of fitness to drive in patients with non-AD dementia, however, clinical interviews (AUC=0.559) and driving simulator rides (AUC=0.404) were not. The fitness-to-drive assessment strategy with the 3 types of assessment combined (AUC=0.635) was not found to significantly predict fitness to drive in non-AD dementia. Different types of dementia require different measures and assessment strategies.


Assuntos
Doença de Alzheimer/classificação , Exame para Habilitação de Motoristas , Condução de Veículo/psicologia , Idoso , Feminino , Humanos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Tempo de Reação
20.
Pharmacopsychiatry ; 50(5): 182-188, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28672405

RESUMO

Introduction Depression is a mental disorder likely to affect everyday functions. The present study aimed to assess actual driving performance of depressed patients who were without specific antidepressant treatment or received long-term antidepressant treatment. Methods A standardized on-the-road driving test was used to assess standard deviation of lateral position (SDLP) in 3 patient groups receiving either no antidepressant treatment (with or without benzodiazepine medication) or treatment with selective serotonin/noradrenalin reuptake inhibitors for a period of 6-52 weeks. Severity of depression was assessed using Beck's Depression Inventory and the Hamilton Depression Rating Scale. The performance of patient groups was compared to healthy controls. Results The mean SDLP of untreated and treated patients was significantly higher than that of healthy controls. Driving impairment in the long-term treated group was significantly less than in the untreated groups. SDLP was positively correlated to severity of depression across all groups. Discussion It is concluded that symptoms of depression are a major cause of driving impairment. Reductions in severity of depression through antidepressant treatment reduce severity of driving impairment.


Assuntos
Antidepressivos/efeitos adversos , Antidepressivos/uso terapêutico , Condução de Veículo/psicologia , Depressão/tratamento farmacológico , Depressão/psicologia , Adulto , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Quimioterapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Adulto Jovem
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