Heart rate variability and falls in Huntington's disease.

PURPOSE: Persons with Huntington's disease (HD) have a high incidence of falls. Autonomic nervous system dysfunction has been reported even in early stages of this disease. To date, there has been no analysis of the relationship between heart rate variability (HRV) and falls in this patient population. The aim of the study reported here was to evaluate the relationship between HRV and falls in persons with HD. METHODS: Huntington's disease patients enrolled in a prospective study on fear of falling and falls were assessed using short-term HRV analyses and blood pressure measures in both the resting and standing states. Time-frequency domains and nonlinear parameters were calculated. Data on falls, the risk of falling (RoF) and disease-specific scales were collected at baseline and at the end of the 6-month follow-up. RESULTS: Of the 24 HD patients who were invited to participate in the study, 20 completed the baseline analysis and 18 completed the 6-month follow-up. At baseline, seven (35%) HD patients reported at least one fall (single fallers) and 13 (65%) reported ≥ 2 falls (recurrent fallers) in the previous 12 months. At baseline, recurrent fallers had lower RMSSD (root mean square of successive RR interval differences) in the resting state (RMSSD-resting), higher LF/HF (low/high frequency) ratio in both states and higher DFA-α1 parameter (detrended fluctuation analyses over the short term) in both states. This association was similar at the 6-month follow-up for recurrent fallers, who showed lower RMSSD-resting and higher LF/HF ratio in the standing state (LF/HF-standing) than single fallers. Significant correlations were found between the number of falls, RMSSD-resting and LF/HF-standing. No differences were found between recurrent and single fallers for any blood pressure measures. CONCLUSIONS: The observed HRV pattern is consistent with a higher sympathetic prevalence associated with a higher RoF. Reduced parasympathetic HRV values in this patient population predict being a recurrent faller at 6 months of follow-up, independently of orthostatic phenomena.

Brain Structural and Amyloid Correlates of Recovery From Semantic Interference in Cognitively Normal Individuals With or Without Family History of Late-Onset Alzheimer's Disease.

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer's disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer's disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS). The authors evaluated the LASSI-L, a test tapping frPSI and other types of semantic interference and delayed recall on the RAVLT, along with 3-T MRI volumetry and positron emission tomography Pittsburgh compound B, in 27 O-LOAD and 18 CS with equivalent age, sex, years of education, ethnicity, premorbid intelligence, and mood symptoms. Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases. Structural correlates of both cognitive dimensions were different in CS and O-LOAD, involving brain regions concerned with autonomic, motor, and motivational control in the former, and regions traditionally implicated in Alzheimer's disease in the latter. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD. The neuroimaging correlates of such cognitive measure in those with one parent with LOAD involve Alzheimer's-relevant brain regions even at a relatively young age.

Melatonin, mitochondria, and the metabolic syndrome.

A number of risk factors for cardiovascular disease including hyperinsulinemia, glucose intolerance, dyslipidemia, obesity, and elevated blood pressure are collectively known as metabolic syndrome (MS). Since mitochondrial activity is modulated by the availability of energy in cells, the disruption of key regulators of metabolism in MS not only affects the activity of mitochondria but also their dynamics and turnover. Therefore, a link of MS with mitochondrial dysfunction has been suspected since long. As a chronobiotic/cytoprotective agent, melatonin has a special place in prevention and treatment of MS. Melatonin levels are reduced in diseases associated with insulin resistance like MS. Melatonin improves sleep efficiency and has antioxidant and anti-inflammatory properties, partly for its role as a metabolic regulator and mitochondrial protector. We discuss in the present review the several cytoprotective melatonin actions that attenuate inflammatory responses in MS. The clinical data that support the potential therapeutical value of melatonin in human MS are reviewed.

Assessing the efficacy of melatonin to curtail benzodiazepine/Z drug abuse.

The abuse of benzodiazepine (BZP) and Z drugs has become, due to the tolerance and dependence they produce, a serious public health problem. Thirty years ago, we demonstrated in experimental animals the interaction of melatonin with central BZD receptors, and in 1997 we published the first series of elderly patients who reduced BZP consumption after melatonin treatment. Almost every single neuron in the hypothalamic suprachiasmatic nuclei (SCN), the central pacemaker of the circadian system, contains γ-aminobutyric acid (GABA) and many results in animals point out to a melatonin interaction with GABA-containing neurons. In addition, central-type BZD antagonism, that obliterates GABAA receptor function, blunted most behavioral effects of melatonin including sleep. Melatonin is involved in the regulation of human sleep. This is supported by the temporal relationship between the rise of plasma melatonin levels and sleep propensity as well as by the sleep-promoting effects of exogenously administered melatonin. Both meta-analyses and consensus agreements give support to the therapeutic use of melatonin in sleep disorders. This action is attributed to MT1 and MT2 melatoninergic receptors localized in the SCN, as well as in other brain areas. This review discusses available data on the efficacy of melatonin to curtail chronic BZD/Z drug use in insomnia patients. A major advantage is that melatonin has a very safe profile, it is usually remarkably well tolerated and, in some studies, it has been administered to patients at very large doses and for long periods of time, without any potentiality of abuse. Further studies on this application of melatonin are warranted.

Circadian rhythm of autonomic cardiovascular control during Mars500 simulated mission to Mars.

INTRODUCTION: The Mars500 project was conceived to gather knowledge about the psychological and physiological effects of living in an enclosed environment during 520 d as would be required for a real mission to Mars. Our objective was to investigate the circadian profile of heart rate variability (HRV) in the context of the Mars500 study. METHODS: Before, during, and after confinement, 24-h EKG records were obtained from the six crewmembers who participated in the mission. Autonomic activity was evaluated through time and frequency domain indexes of HRV analysis. Circadian rhythmicity was assessed both by averaging hourly HRV along wake and sleep scheduled periods and by fitting a 24-h harmonic to the hourly means. RESULTS: During confinement, wake HRV showed (mean +/- SE) a progressive increase in mean RR interval (from 778 +/- 24 ms to 916 +/- 42 ms), and in the amplitude (values are wavelet power coefficients) of very low (from 13.3 +/- 0.3 to 14.1 +/- 0.2) and high (from 7.8 +/- 0.4 to 8.3 +/- 0.3) frequency components. During sleep, the relative amplitude of the high frequency component of HRV decreased (from 11.8 +/- 1.6 to 9.4 +/- 1.8 normalized units). Overall, sleep-wake differences of HRV showed a progressive decrease of the relative amplitude of the high frequency component. Also, circadian HRV rhythms were dampened during confinement. DISCUSSION: Data revealed diminished amplitude of the rest-activity pattern of the autonomic nervous system parasympathetic function. Reduced daylight exposure and mood changes could account for this observation.

An Exploratory Study of Sleep-Wake Differences of Autonomic Activity in Patients with Mild Cognitive Impairment: The Role of Melatonin as a Modulating Factor.

Purpose: The objective of the present study was to assess sleep-wake differences of autonomic activity in patients with mild cognitive impairment (MCI) compared to control subjects. As a post-hoc objective, we sought to evaluate the mediating effect of melatonin on this association. Patients and Methods: A total of 22 MCI patients (13 under melatonin treatment) and 12 control subjects were included in this study. Sleep-wake periods were identified by actigraphy and 24hr-heart rate variability measures were obtained to study sleep-wake autonomic activity. Results: MCI patients did not show any significant differences in sleep-wake autonomic activity when compared to control subjects. Post-hoc analyses revealed that MCI patients not taking melatonin displayed lower parasympathetic sleep-wake amplitude than controls not taking melatonin (RMSSD -7 ± 1 vs 4 ± 4, p = 0.004). In addition, we observed that melatonin treatment was associated with greater parasympathetic activity during sleep (VLF 15.5 ± 0.1 vs 15.1 ± 0.1, p = 0.010) and in sleep-wake differences in MCI patients (VLF 0.5 ± 0.1 vs 0.2 ± 0.0, p = 0.004). Conclusion: These preliminary findings hint at a possible sleep-related parasympathetic vulnerability in patients at prodromal stages of dementia as well as a potential protective effect of exogenous melatonin in this population.

Sleep-wake differences in heart rate variability during a 105-day simulated mission to Mars.

INTRODUCTION: In prolonged spaceflights the effect of long-term confinement on the autonomic regulation of the heart is difficult to separate from the effect of prolonged exposure to microgravity or other space-related stressors. Our objective was to investigate whether the sleep-wake variations in the autonomic control of the heart are specifically altered by long-term confinement during the 105-d pilot study of the Earth-based Mars500 project. METHODS: Before (pre), during (T1: 30, T2: 70, andT3: 100 d), and after (post) confinement, 24-h EKG records were obtained from the six crewmembers that participated in the mission. Sleep and wake periods were determined by fitting a square wave to the data. Autonomic activity was evaluated through time and frequency domain indexes of heart rate variability (HRV) analysis during wake and sleep periods. RESULTS: During confinement, wake HRV showed decreased mean heart rate and increased amplitude at all frequency levels, particularly in the very low (pre: 13.3 +/- 0.2; T1: 13.9 +/- 0.3; T2: 13.9 +/- 0.2; T3: 13.9 +/- 0.2; post: 13.2 +/- 0.2) and high (pre: 7.6 +/- 0.4; T1: 8.3 +/- 0.5; T2: 8.2 +/- 0.4; T3: 8.1 +/- 0.4; post: 7.6 +/- 0.3) frequency components (values expressed as mean +/- SE of wavelet power coefficients). Sleep HRV remained constant, while sleep-wake high frequency HRV differences diminished. DISCUSSION: The observed autonomic changes during confinement reflect an increase in parasympathetic activity during wake periods. Several factors could account for this observation, including reduced daylight exposure related to the confinement situation.

Higher autonomic activation predicts better performance in iowa gambling task.

OBJECTIVE: To evaluate the relationship between the autonomic nervous system basal state and performance in decision-making tasks. BACKGROUND: The link between performance in decision-making tasks and acute changes in autonomic parameters during their execution has been extensively investigated. However, there is lacking evidence regarding the relationship between decision making and basal autonomic state. METHODS: Resting autonomic nervous system activity in 18 healthy individuals was assessed by means of heart rate variability (HRV) analysis before conducting 3 different decision-making tasks: an ambiguous one, the Iowa Gambling Task; a test that assesses risk-taking behavior, the Game of Dice Task; and a test that assesses reversal learning behavior, the Reversal Learning Task. The tasks were administered in a random manner. RESULTS: There was a direct correlation between the Iowa Gambling Task net score and the resting low frequency HRV (r = 0.73; P < 0.001), which is strongly influenced by sympathetic activity. No correlations were found between HRV and the Game of Dice Task net score or the Reversal Learning Task last error trial. CONCLUSIONS: The results are compatible with the idea that a higher basal activation of autonomic nervous system is beneficial for subsequent decision-making process.

Autonomic nervous system activation during social cognition tasks in patients with schizophrenia and their unaffected relatives.

OBJECTIVE: The objective of the study was to determine whether patients with schizophrenia and their unaffected first-degree relatives have abnormal autonomic nervous system (ANS) responses to social cognition tasks. BACKGROUND: Social cognition impairments are significant in schizophrenia. ANS activity has been shown to be abnormal in schizophrenia patients, and some of the abnormalities seem to be shared by patients' unaffected relatives. METHOD: Heart rate variability (HRV) was measured at rest and during social cognition tasks, in patients with schizophrenia, their nonpsychotic first-degree relatives, and matched healthy controls (n=19 in each group). RESULTS: Social cognition tasks induced a shortening of the RR interval in unaffected relatives, but not in patients. Social cognition tasks generated decreases in high-frequency (indicating cardiac vagal activity) and low-frequency (reflecting predominantly sympathetic activity) HRV in patients. In relatives, the decrease occurred in the high-frequency component only. Low-frequency HRV was higher in patients during a theory of mind task than a control task. These changes were not observed in the controls. CONCLUSIONS: Social cognitive tasks induce a pattern of peripheral autonomic activity different from that seen in generic arousal responses, and this pattern is abnormal in schizophrenia patients. Autonomic abnormalities in unaffected first-degree relatives seem restricted to the parasympathetic division of the ANS.

Heart rate nonlinear dynamics during sudden hypoxia at 8230 m simulated altitude.

OBJECTIVE: Acute hypobaric hypoxia is associated with autonomic changes that bring a global reduction of linear heart rate variability (HRV). Although changes in nonlinear HRV can be associated with physiologic stress and are relevant predictors of fatal arrhythmias in ischemic heart disease, to what extent these components vary in sudden hypobaric hypoxia is not known. METHODS: Twelve military pilots were supplemented with increasing concentrations of oxygen during decompression to 8230 m in a hypobaric chamber. Linear and nonlinear HRV was evaluated at 8230 m altitude before, during, and after oxygen flow deprivation. Linear HRV was assessed through traditional time-domain and frequency-domain analysis. Nonlinear HRV was quantified through the short-term fractal correlation exponent alpha (alphas) and the Sample Entropy index (SampEn). RESULTS: Hypoxia was related to a decrease in linear HRV indexes at all frequency levels. A non-significant decrease in alphas (basal, 1.39 +/- 0.07; hypoxia, 1.11 +/- 0.13; recovery, 1.41 +/- 0.05; P = .054) and a significant increase in SampEn (basal, 1.07 +/- 0.11; hypoxia, 1.45 +/- 0.12; recovery, 1.43 +/- 0.09; P = .018) were detected. CONCLUSIONS: The observed pattern of diminished linear HRV and increased nonlinear HRV is similar to that seen in subjects undergoing heavy exercise or in patients with ischemic heart disease at high risk for ventricular fibrillation.

Sleep disruption in medicine students and its relationship with impaired academic performance: A systematic review and meta-analysis.

Sleep disruption severely impairs learning ability, affecting academic performance in students. This systematic review and meta-analysis aimed at assessing the prevalence of sleep disruption in medical students and its relationship with academic performance. PubMed, Web of Sciences, EBSCO and SciELO databases searches allowed to retrieve 41 papers with data about the prevalence of sleep deprivation, 20 of which also contained data on its association with academic performance. Poor sleep quality was reported by 5646 out of 14,170 students in 29 studies (39.8%, 95% confidence interval = 39.0-40.6%), insufficient sleep duration by 3762/12,906 students in 28 studies (29.1%, 23.3-29.9%) and excessive diurnal sleepiness by 1324/3688 students in 13 studies (35.9%, 34.3-37.4). Academic grades correlated significantly with sleep quality scores (r, 95% CI = 0.15, 0.05-0.26, random-effects model; p = 0.002, n = 10,420 subjects, k = 15 studies) and diurnal sleepiness (r = -0.12, -0.19/-0.06 under the fixed effects model, p < 0.001, n = 1539, k = 6), but not with sleep duration (r = 0.03, -0.12/0.17 under the random-effects model, p = 0.132, n = 2469, k = 9). These findings advocate for an urgent intervention aiming at improving sleep quality among medical students as a way of increasing academic achievements and, ultimately, the quality of health care.

Subjective time estimation in Antarctica: The impact of extreme environments and isolation on a time production task.

Interval timing measures time estimation in the seconds-to-minutes range. Antarctica provides a real-world context to study the effect of extreme photoperiods and isolation on time perception. The aim of this study was to explore interval timing as a cognitive measure in the crew of Belgrano II Argentine Antarctic Station. A total of 13 subjects were assessed for interval timing in short (3 s), intermediate (6 s) and long (12 s) duration stimuli. Measures were taken during the morning and evening, five times along the year. Significant variations were found for 3 s and 6 s during the morning and 6 s during the evening. Results suggest an impact of isolation on morning performances and an effect of the polar night on evening measures. These findings shed some light on the use of interval timing as a cognitive test to assess performance in extreme environments.

Sleep misalignment and circadian rhythm impairment in long-haul bus drivers under a two-up operations system.

OBJECTIVES: The objective of the study was to describe working and sleep conditions and to assess how sleep opportunities are associated with obtained sleep and alertness, in a sample of long-haul bus drivers working with a two-up operations system. METHODS: Measures of subjective sleep and sleepiness, actigraphy, circadian temperature rhythm, and psychomotor vigilance tasks were obtained from a sample of 122 drivers from Argentina. Variables were compared between high and low fatigue risk groups, which were formed using a median split of a fatigue risk score. The score was calculated based on drivers' total working hours, maximum shift duration, minimum short break duration, maximum night work per seven days, and long break frequencies. RESULTS: Considering a standardized one-day period, sleep in the bus accounted for 1.9±0.1 h of total sleep (57±1% efficiency), sleep at destination for 1.6±0.2 h of total sleep (90±1% efficiency), and sleep at home for 3.8±0.2 h of total sleep (89±1% nap efficiency and 90±1% anchor sleep efficiency). In drivers exposed to high-risk working schedules, the circadian temperature rhythm was weaker (lower % of variance explained by the model) (22.0±1.7% vs. 27.6±2.0%, p <0.05) and without a significant acrophase. CONCLUSIONS: Drivers obtained a total amount of weekly sleep similar to the recommended levels for adults, but distributed at different locations and at different times during the day. High-risk working schedules were associated with disruption of circadian temperature rhythms. These results point out to the need of the implementation of shift-work scheduling strategies to minimize sleep misalignment and circadian desynchronization in long-haul bus drivers.

Heart rate variability response to mental arithmetic stress is abnormal in first-degree relatives of individuals with schizophrenia.

BACKGROUND: Schizophrenia patients exhibit an abnormal autonomic response to mental stress. We sought to determine the cardiac autonomic response to mental arithmetic stress in their unaffected first-degree relatives. METHODS: Heart rate variability (HRV) analysis was performed on recordings obtained before, during, and after a standard mental arithmetic task to induce mental stress. 22 unaffected first-degree relatives of patients meeting DSM-IV criteria for schizophrenia (R) and 22 healthy individuals (C) were included in this study. RESULTS: Patients' relatives (R) had a normal response to the mental arithmetic stress test, showing an increased heart rate compared with controls. They also displayed the characteristic pattern of relative contributions of HRV components that consists of increased low-frequency (LF) HRV and decreased high-frequency (HF) HRV. Recovery of the resting pattern of HRV immediately after stress termination was observed in healthy subjects (LF 62+/-16% vs. 74+/-10% , HF 37+/-16% vs. 25+/-10%, F=9.616, p=0.004), but not in patients' relatives (LF 60+/-19% vs. 70+/-13%, HF 40+/-19% vs. 29+/-13%, F=8.4, p=0.056). CONCLUSIONS: First-degree relatives of schizophrenia patients exhibit an abnormal pattern of protracted response to mental arithmetic stress, though less intense than that observed in patients in a previous study. This suggests that a pattern of autonomic response to stress may therefore be familial and heritable.

Executive functioning in cognitively normal middle-aged offspring of late-onset Alzheimer's disease patients.

Episodic memory deficits are traditionally seen as the hallmark cognitive impairment during the prodromal continuum of late-onset Alzheimer's disease (LOAD). Previous studies identified early brain alterations in regions subserving executive functions in asymptomatic, middle-aged offspring of patients with LOAD (O-LOAD), suggesting that premature episodic memory deficits could be associated to executive dysfunction in this model. We hypothesized that O-LOAD would exhibit reduced executive performance evidenced by increased errors and decreased strategy use on an episodic memory task. We assessed 32 asymptomatic middle-aged O-LOAD and 28 age-equivalent control subjects (CS) with several tests that measure executive functions and the Rey Auditory Verbal Learning Test (RAVLT) to measure memory performance. All tests were scored using both traditional and process scores (quantification of errors and strategies underlying overall performance). T-tests were used to compare performance between both groups and Spearman correlations were implemented to measure associations between variables. O-LOAD participants exhibited decreased executive performance compared to CS as it relates to initiation time (Tower of London), mental switching (Trail Making Test B), and interference effects (Stroop Word-Color condition). Traditional RAVLT measures showed a poorer performance by O-LOAD and RAVLT process scores revealed increased interference effects on this group. Positive correlations (rs) were found between the executive measures and several RAVLT measures for O-LOAD but not for CS. In conclusion, O-LOAD participants exhibited early subtle cognitive changes in executive processing. Observed memory difficulties may be associated in part to executive deficits suggesting an interplay between memory and executive functions. Process score impairments were observed earlier than clinical decline on neuropsychological scores in this at-risk cohort and might be useful cognitive markers of preclinical LOAD.

Sleep, napping and alertness during an overwintering mission at Belgrano II Argentine Antarctic station.

During Antarctic isolation personnel are exposed to extreme photoperiods. A frequent observation is a sleep onset phase delay during winter. It is not known if, as a result, daytime sleeping in the form of naps increases. We sought to assess sleep patterns - with focus on daytime sleeping - and alertness in a Latin American crew overwintering in Argentine Antarctic station Belgrano II. Measurements were collected in 13 males during March, May, July, September and November, and included actigraphy and psychomotor vigilance tasks. Sleep duration significantly decreased during winter. A total of eight participants took at least one weekly nap across all measurement points. During winter, the nap onset was delayed, its duration increased and its efficiency improved. We observed a significant effect of seasonality in the association of evening alertness with sleep onset. Our results replicate previous findings regarding sleep during overwintering in Antarctica, adding the description of the role of napping and the report of a possible modulatory effect of seasonality in the relation between sleep and alertness. Napping should be considered as an important factor in the scheduling of activities of multicultural crews that participate in Antarctica.

Heart rate variability response to mental arithmetic stress in patients with schizophrenia: autonomic response to stress in schizophrenia.

BACKGROUND: The vulnerability-stress hypothesis is an established model of schizophrenia symptom formation. We sought to characterise the pattern of the cardiac autonomic response to mental arithmetic stress in patients with stable schizophrenia. METHODS: We performed heart rate variability (HRV) analysis on recordings obtained before, during, and after a standard test of autonomic function involving mental stress in 25 patients with DSM-IV schizophrenia (S) and 25 healthy individuals (C). RESULTS: Patients with schizophrenia had a normal response to the mental arithmetic stress test. Relative contributions of low-frequency (LF) HRV and high-frequency (HF) HRV influences on heart rate in patients were similar to controls both at rest (LF 64+/-19% (S) vs. 56+/-16% (C); HF 36+/-19% (S) vs. 44+/-16% (C), t=1.52, p=0.136) and during mental stress, with increased LF (S: 76+/-12%, C: 74+/-11%) and decreased HF (S: 24+/-12%, C: 26+/-11%) in the latter study condition. Whilst healthy persons recovered the resting pattern of HRV immediately after stress termination (LF 60+/-15%, HF 40+/-15%, F=18.5, p<0.001), in patients HRV remained unchanged throughout the observed recovery period, with larger LF (71+/-17%) and lower HF (29+/-17%) compared with baseline (F=7.3, p=0.013). CONCLUSIONS: Patients with schizophrenia exhibit a normal response to the mental arithmetic stress test as a standard test of autonomic function but in contrast with healthy individuals, they maintain stress-related changes of cardiac autonomic function beyond stimulus cessation.

Nonlinear analysis of heart rate variability in patients with eating disorders.

Patients with anorexia nervosa or bulimia nervosa often have signs of autonomic dysfunction potentially deleterious to the heart. The aim of this study was to ascertain the nonlinear properties of heart rate variability in patients with eating disorders. A group of 33 women with eating disorders (14 anorexia, 19 bulimia) and 19 healthy controls were included in the study. Conventional time- and frequency-domain heart rate variability measurements, along with nonlinear heart rate variability measurements including the short-term fractal scaling exponent alpha and approximate entropy (ApEn) were calculated. Anorexia nervosa patients exhibited decreased values of alpha, while bulimia nervosa patients had decreased values of ApEn. Low-frequency heart rate variability was decreased in patients with anorexia. In conclusion, these results are compatible with the view that a more severe alteration of cardiac autonomic function is present in anorexia than in bulimia.

Hours of service regulations for professional drivers in continental Latin America.

OBJECTIVES: To describe the hours of service provisions in continental Latin America. DESIGN: Information on regulations of service hours was extracted from either the national transportation authorities or ministries of transportation (or the equivalent institution) from each country. SETTING: Seventeen sovereign countries in continental Latin America (Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Ecuador, El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama, Paraguay, Peru, Uruguay, Venezuela). PARTICIPANTS: N/A INTERVENTION (IF ANY): N/A MEASUREMENT: Data on (a) limit on work hours, (b) mandatory daily time off (or rest), (c) overall schedule (mandatory weekly time off), and (d) daily breaks were extracted and summarized. RESULTS: Of the 17 countries surveyed, 9 countries have provisions limiting the daily amount of hours of service for professional drivers. Ten have provisions for mandatory daily rest, but only 5 have explicit provisions limiting the number of continuous working days, with mandatory uninterrupted time off >35 hours. Eight countries have provisions for mandatory breaks that limit the hours of continuous driving (ranging from 3 to 5:30 hours). CONCLUSION: Regulations that govern a population with 6 million injuries and over 100,000 deaths per year due to motor vehicle accidents leave important gaps. A minority, 6, of the countries regulated all 3 aspects; daily hours, breaks, and time off, and 3 regulate none of these. The regulations are less precise and restrictive than those in high-income countries, despite the doubled road injury mortality, and likely expose professional drivers and other road users to an increased risk of fatigue-related accidents.