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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem 4 Functional and Economic Impact of Sleep Loss and Sleep-Related Disorders CHAPTER SUMMARY Sleep loss and sleep disorders affect an individual’s performance, safety, and quality of life. Almost 20 percent of all serious car crash injuries in the general population are associated with driver sleepiness, independent of alcohol effects. Further, sleep loss and sleep disorders have a significant economic impact. The high estimated costs to society of leaving the most prevalent sleep disorders untreated are far more than the costs that would be incurred by delivering adequate treatment. Hundreds of billions of dollars a year are spent on direct medical costs associated with doctor visits, hospital services, prescriptions, and over-the-counter drugs. Compared to healthy individuals, individuals suffering from sleep loss, sleep disorders, or both are less productive, have an increased health care utilization, and an increased likelihood of accidents.
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem The public health consequences of sleep loss, night work, and sleep disorders are far from benign. Some of the most devastating human and environmental health disasters have been partially attributed to sleep loss and night shift work-related performance failures, including the tragedy at the Bhopal, India, chemical plant; the nuclear reactor meltdowns at Three Mile Island and Chernobyl; as well as the grounding of the Star Princess cruise ship and the Exxon Valdez oil tanker (NCSDS, 1994; NTSB, 1997; Moss and Sills, 1981; United States Senate Committee on Energy and National Resources, 1986; USNRC, 1987; Dinges et al., 1989). Each of these incidents not only cost millions of dollars to clean up, but also had a significant impact on the environment and the health of local communities. Less visible consequences of sleep conditions take a toll on nearly every key indicator of public health: mortality, morbidity, performance, accidents and injuries, functioning and quality of life, family well-being, and health care utilization. This chapter begins with an overview of the consequences of sleep loss and sleep disorders on an individual’s performance, safety, and quality of life. Drawing on the available body of evidence, the chapter then describes the economic impact of sleep loss and sleep disorders. PERFORMANCE AND COGNITION DEFICITS Nearly all types of sleep problems are associated with performance deficits in occupational, educational, and other settings. The deficits include attention, vigilance, and other measures of cognition, including memory and complex decision making. This section addresses sleep loss and then turns to sleep-disordered breathing and other sleep disorders. Sleep Loss Affects Cognitive Performance Sleep loss had been largely dismissed as the cause of poor cognitive performance by early, yet poorly designed, research. The prevailing view until the 1990s was that people adapted to chronic sleep loss without adverse cognitive effects (Dinges et al., 2005). More recent research has revealed sleep loss-induced neurobehavioral effects, which often go unrecognized by the affected individuals. The neurobehavioral impact extends from simple measures of cognition (i.e., attention and reaction time) to far more complex errors in judgment and decision making, such as medical errors, discussed below and in Box 4-1. Performance effects of sleep loss include the following: Involuntary microsleeps occur. Attention to intensive performance is unstable, with increased errors of omission and commission.
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem BOX 4-1 Reducing Interns’ Work Hours in Intensive Care Units Lowers Medical Errors The longstanding debate over medical residents’ lengthy work hours pits patient safety advocates against those who view the practice as necessary for continuity of care, preparation for medical practice, and cost containment (Steinbrook, 2002). After years of debate, and the threat of federal regulations, the Accreditation Council for Graduate Medical Education changed its requirements in 2003 to restrict residents’ work hours to about 80 hours per week (ACGME, 2003). The policy permits no more than a maximum shift duration of 24 hours and overnight call no more than every third night. Does this revised policy protect patients? The Harvard Work Hours, Health and Safety Study compared a schedule of about 80 hours per week (termed the traditional schedule) with a reduced schedule that eliminated shifts of 24 hours or more and kept work hours under 63 per week. The trial was conducted in intensive care units because they typically have the longest hours and the highest rates of errors. The intervention schedule not only enhanced interns’ sleep duration and lowered their rate of attentional failures, but also reduced the rate of serious medical errors, according to two articles published in 2004 in the New England Journal of Medicine. In the first article, the investigators used a within-subjects design (n = 20 interns) and validated sleep duration by polysomnography and attentional failures by slow-rolling eye movements recorded during continuous electro-oculography. Under the intervention schedule, the article reported that residents slept nearly 6 more hours per week, and they experienced half the rate of attentional failures during on-call nights than under the traditional schedule (Lockley et al., 2004). The second article on medical errors reported results after randomizing interns to either the traditional or reduced schedule (Landrigan et al., 2004). Two physicians who directly observed the interns without awareness of their schedules identified serious medical errors, defined as causing or having the potential to cause harm to a patient. Errors were recorded by type (medication, diagnosis, and procedure) and in terms of number, or rate per 1,000 patient days. The study covered a total of 2,203 patient-days involving 634 admissions. Under the traditional schedule, interns made nearly 21 percent more medication errors and at least five times more diagnostic errors. Overall, the unitwide rate of serious medical errors was 22 percent higher in the traditional versus the intervention schedule (P < .001) as shown in the table below. The investigators concluded that reducing interns’ hours can lower the occurrence of serious medical errors in the intensive care unit.
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem Incidence of Serious Medical Errors (rate/1,000 patient days) Variable Traditional Schedule Intervention Schedule P Value Serious medical errors made by interns Serious medical errors 176 (136.0) 91 (100.1) < 0.001 Preventable adverse events 27 (20.9) 15 (16.5) 0.21 Intercepted serious errors 91 (70.3) 50 (55.0) 0.02 Nonintercepted serious errors 58 (44.8) 26 (28.6) < 0.001 Types of serious medical errors made by interns Medication 129 (99.7) 75 (82.5) 0.03 Procedural 11 (8.5) 6 (6.6) 0.34 Diagnostic 24 (18.6) 3 (3.3) < 0.001 Other 12 (9.3) 7 (7.7) 0.47 All serious medical errors, unitwide Serious medical errors 250 (193.2) 144 (158.4) < 0.001 Preventable adverse events 50 (38.6) 35 (38.5) 0.91 Intercepted serious errors 123 (95.1) 63 (69.3) < 0.001 Nonintercepted serious errors 77 (59.5) 46 (50.6) 0.14 Types of serious medical errors made by interns Medication 175 (135.2) 105 (115.5) 0.03 Procedural 18 (13.9) 11 (12.1) 0.48 Diagnostic 28 (21.6) 10 (11.0) < 0.001 Other 29 (22.4) 18 (19.8) 0.45 SOURCE: Landrigan et al. (2004). Cognitive slowing occurs in subject-paced tasks, while time pressure increases cognitive errors. Response time slows. Performance declines in short-term recall of working memory. Performance requiring divergent thinking deteriorates. Learning (acquisition) of cognitive tasks is reduced. An increase in response suppression errors in tasks requiring normal primarily prefrontal cortex function.
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem The likelihood of response preservation on ineffective solutions is increased. Compensatory efforts to remain behaviorally effective are increased. Although tasks may be done well, performance deteriorates as tasks duration increases (Durmer and Dinges, 2005). Attention and reaction time are altered by experimental sleep loss, which leads to cumulative, dose-dependent deterioration of attention and reaction time (Figure 4-1). Deterioration is measured in part using the psy- FIGURE 4-1 Repeated nights of sleep loss have cumulative cognitive impairment. NOTE: B, baseline day. SOURCES: (A) Van Dongen et al. (2003); (B) Belenky et al. (2003).
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem chomotor vigilance task (PVT), a test that requires continuous attention to detect randomly occurring stimuli and that is impervious to aptitude and learning effects. In one study 48 healthy subjects were randomized to 4, 6, or 8 hours time in bed for 14 days (Van Dongen et al., 2003). Investigators found a dose-dependent effect, which increased over time (Figure 4-1A). Performance deficits in individuals who slept 6 hours or less per night were similar to those observed in individuals after two nights of total sleep deprivation. Most striking was that study subjects remained largely unaware of their performance deficits, as measured by subjective sleepiness ratings. A second study (Belenky et al., 2003) showed a similar dose-dependent, cumulative effect over 7 days of sleep loss in 66 healthy volunteers (Figure 4-1B). Subjects were followed for 3 days after the period of sleep restriction, during which time they recovered, but not enough to return to their baseline levels. Imaging studies have demonstrated a physiological basis for cognitive impairments with sleep loss that has been linked with metabolic declines in the frontal lobe of the brain (Thomas et al., 2000). Although there is not a large body of evidence, associations are also likely between sleep loss and increased risk taking (Roehrs et al., 2004). Sleep Loss in Adolescents and Academic Performance Sleep loss in adolescence is common and grows progressively worse over the course of adolescence, according to studies from numerous countries (Wolfson and Carskadon, 2003; Howell et al., 2004). Average sleep duration diminishes by 40 to 50 minutes from ages 13 to 19. Despite the physiological need for about 9 hours of sleep, sleep duration, across this age span, averages around 7 hours and about a quarter of high school and college students are sleep deprived (Wolfson and Carskadon, 1998). Research indicates that patterns of shortened sleep occur in the preadolescent period and may be most marked in African American boys, compared to white children or African American girls (Spilsbury et al., 2004). The decline in adolescent sleep duration is attributed to psychological and social changes, including growing desire for autonomy, increased academic demands, and growing social and recreational opportunities, all of which take place in spite of no change in rise time for school (Figure 4-2) (Wolfson and Carskadon, 1998). Furthermore, the need to earn income adds to the burden. Students who worked 20 or more hours weekly, compared with those who worked less than 20 hours, were found to go to bed later, sleep fewer hours, oversleep, and fall asleep more in class (Millman et al., 2005). Sleep loss affects alertness, attention, and other cognitive functions in adolescents (Randazzo et al., 1998), but demonstrating a causal relationship between sleep loss and academic performance has been difficult. Most studies attempting to link the two are cross-sectional in design, based on
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem FIGURE 4-2 Sample distribution of sleep patterns. SOURCE: Wolfson and Carskadon (1998).
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem self-reporting of grades and sleep times, and lack a control for potential confounders (Wolfson and Carskadon, 2003). An association between short sleep duration and lower academic performance has been demonstrated (Wolfson and Carskadon, 1998; Drake et al., 2003; Shin et al., 2003), but the question of causality has not been resolved by longitudinal studies. A 3-year study of 2,200 middle school students did not find that sleep loss resulted in lower academic performance. It only found a cross-sectional association at the beginning of the study. However, by the end of the study, as sleep time worsened, grades did not proportionately decrease (Fredriksen et al., 2004). A study of the Minneapolis School District, which delayed start times for its high schools by almost 1.5 hours (from 7:15 a.m. to 8:40 a.m.), found significant improvements in sleep time, attendance, and fewer symptoms of depressed mood (Wahlstrom et al., 2001). Further, there was a trend toward better grades, but not of statistical significance. The study compared grades over the 3 years prior to the change with grades 3 years afterwards. Much of the difficulty in studying sleep loss and its relation to academic performance stems from multiple, often unmeasured, environmental factors that affect sleep (such as school demands, student employment after school, family influences, TV viewing, and Internet access). These are set against the rapid developmental and physiological changes occurring in adolescence. Another difficulty is the challenge of objectively assessing school performance (Wolfson and Carskadon, 2003). Additional robust intervention studies are needed to determine the effect of having later school start times on student performance. However, a confounder to later school start times is the potential onset of sleep phase delay during middle school (seventh and eighth grade). Moving middle school start time early to compensate for later high school start time may be problematic for the middle school children. There have been no studies that have examined effects of early start time on elementary-aged children (Wolfson and Carskadon, 2003). An alternative to changing the school starting times might be to implement bright light therapy in early morning classes for high school students as a means to change the circadian timing system of these students and thereby enable earlier sleep schedules (Wolfson and Carskadon, 2003). Sleep Loss and Medical Errors The Institute of Medicine’s report To Err Is Human estimated that as many as 98,000 deaths—due to medical errors—occur annually in United States hospitals (IOM, 2000). Long work hours and extended shifts among hospital workers are now known to contribute to the problem. Since the report’s release, several new studies, discussed below, have found strong
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem relationships between sleep loss, shift duration, and medical errors among medical residents. Medical residents work longer hours than virtually all other occupational groups (Steinbrook, 2002). During the first year, medical residents frequently work a 24-hour shift every third night (i.e., 96-hours per week). Two studies found that sleep-deprived surgical residents commit up to twice the number of errors in a simulated laparoscopic surgery (Grantcharov et al., 2001; Eastridge et al., 2003). In a survey of 5,600 medical residents, conducted by the Accreditation Council for Graduate Medical Education, total work time was inversely correlated with reported sleep time. Residents who worked more than 80 hours per week were 50 percent more likely than those working less than 80 hours to report making a significant medical error that led to an adverse patient outcome (Baldwin and Daugherty, 2004). The strongest evidence tying medical errors to sleep-related fatigue from extended work hours comes from an intervention trial designed to limit residents’ work hours (Box 4-1). Earlier attempts to demonstrate patient safety benefits by reducing resident hours were beset by methodological problems (Fletcher et al., 2004). Residents are not the only health professionals to report medical errors in association with short sleep. Nurses who completed logbooks recording their schedule length, sleep, and errors, reported 3.3 times more medical errors during 12.5 hour shifts than 8.5 hour shifts (Rogers et al., 2004). Nearly 40 percent of the nurses reported having 12-hour shifts; and although their sleep duration was not directly studied, the findings suggest that fatigue is a major factor. Obstructive Sleep Apnea Is Associated with Development, Cognition, and Behavior in Children Children with obstructive sleep apnea (OSA) often have problems in development, cognition, behavior, and academic performance, according to detailed reviews of the evidence (Schechter, 2002; Bass et al., 2004). The risk of neurobehavioral abnormalities in children with severe OSA is about three times greater than in children without OSA (Schechter, 2002). The contribution of overnight reduction of oxygen levels in the blood (hypoxemia) in comparison to sleep disruption is unclear. One study shows an association with the lowest level of oxygen during sleep and scores in arithmetic (Urschitz et al., 2005), but other studies show cognitive or behavioral deficits in children who snore without severe sleep apnea (Kennedy et al., 2004; Rosen et al., 2004; Gottlieb et al., 2004; O’Hara et al., 2005). Outcome measures used in numerous studies include intelligence quotient, learning and vocabulary, attention, symptoms of attention deficit hyperactivity disorder (ADHD), and academic performance. For example, two historical
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem cohort studies found decrements in intelligence quotient, impaired learning, and vocabulary in children with polysomnography-confirmed cases (Rhodes et al., 1995; Blunden et al., 2000). A study of younger children with sleep apnea also did not find a relationship with academic performance, after adjusting for the effects of socioeconomic status (Chervin et al., 2003). O’Brien and colleagues (2004) found that 35 children with sleep-disordered breathing, compared with matched controls, showed significant deficits in neurocognition, including overall cognitive ability, as well as attention and executive function, but the study did not find behavioral differences. A previous study by the same researchers found higher symptoms of ADHD, according to parents’ reports, in children with OSA (O’Brien et al., 2003). Several other studies have found greater symptoms of ADHD in children with OSA than controls (Weissbluth and Liu, 1983; Stradling et al., 1990; Chervin et al., 1997). The neurobehavioral effects of OSA may be partially reversible with tonsillectomy and adenoidectomy, a surgical procedure that opens the airway. Treatment is related to partial improvement in school performance, cognition, or behavior (Ali et al., 1996; Friedman et al., 2003). A limitation to this work is that it is often difficult to control for the many confounders that influence cognitive function, with a recent study showing that after robustly adjusting for neighborhood socioeconomic status (Emancipator et al., 2006), effects were much attenuated, although they persisted in a subgroup of children who had been born prematurely. No randomized controlled study has been conducted to address the potential reversibility of cognitive deficits with sleep-disordered breathing; such data would more definitively address this situation. Gozal (1998) studied 54 children with sleep-disordered breathing and low school performance. Half of them underwent surgical tonsillectomy and adenoidectomy to treat OSA. Children undergoing the interventions improved their academic performance, compared to untreated children. One problem with the study design; however, was that surgical treatment was not randomly assigned (parents elected whether or not their children could receive surgery). Given the high proportion of children with sleep-disordered breathing, especially in vulnerable groups such as children in minority populations and those born prematurely, there is a large need to address the role of sleep-disordered breathing and its reversibility in these important outcomes. Sleep-Disordered Breathing and Cognitive Impairment in Adults Several cross-sectional studies indicate that sleep-disordered breathing in adults is associated with impaired cognitive function (Greenberg et al., 1987; Bedard et al., 1991; Naegele et al., 1995; Redline et al., 1997; Kim et al., 1997). Cognitive deficits, in turn, partially contribute to poorer work
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem performance (Ulfberg et al., 1996), accidents and injuries, and deterioration of the quality of life (see later sections). A meta-analysis of the case-control studies found that the magnitude of the cognitive disturbance was greatest in individuals with severe OSA. Cognitive domains most affected were attention and executive function (the capacity to plan and organize complex tasks) with only milder effects on memory (Engleman et al., 2000). The meta-analysis also found some cognitive benefit associated with continuous positive airway pressure (CPAP) treatment. In a series of randomized, placebo-controlled crossover trials, people with mild OSA exhibited a trend toward better performance. The failure to detect a robust effect may have been due to the fact that the patients had mild disease, were nonadherent to therapy, or that they had a possibly irreversible component to the cognitive impairment. The cognitive deficits with sleep-disordered breathing are thought to be related to both sleep fragmentation and hypoxemia (Weaver and George, 2005). However, one study showed no clear threshold level between level of hypoxia and performance deficits (Adams et al., 2001). Animal models of chronic episodic hypoxia have led to the hypothesis that cognitive deficits in humans result from injury of nerve cells in the pre-frontal cortex (Beebe and Gozal, 2002), the area of the brain responsible for problem solving, emotion, and complex thought. MOTOR VEHICLE CRASHES AND OTHER INJURIES Motor Vehicle Crashes Sleepiness is a significant, and possibly growing, contributor to serious motor vehicle injuries. Almost 20 percent of all serious car crash injuries in the general population are associated with driver sleepiness, independent of alcohol effects (Connor et al., 2002). Driver sleepiness is most frequently a manifestation of sleep loss, as discussed below, but other sleep disorders, which have lower prevalence, contribute to the problem, including sleep-disordered breathing, restless legs syndrome, and narcolepsy. The 20 percent figure, cited above, is the population-attributable risk, which is a key public health measure indicating what percentage of car crash injuries, including fatal injuries of passengers, could be avoided by eliminating driver sleepiness. The finding was based on a population-based case-control study in a region of New Zealand in which 571 car drivers and a matched control sample were asked detailed questions about measures of acute sleepiness while driving (Connor et al., 2002). The study adjusted for potential confounding factors, including alcohol. Crashes examined in this study involved a hospitalization or death. The greatest risk factor for the crashes was sleep loss and time of day (driving between 2:00 a.m. to 5:00 a.m.), but sleep apnea symptoms were not risk factors.
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Sleep Disorders and Sleep Deprivation: An Unmet Public Health Problem the prevalence and severity of OSA is higher in African Americans compared to whites (Scharf et al., 2004), especially in adults under 25 years of age (Redline et al., 1994; Rosen et al., 2002). Compared to whites, African Americans with OSA are more likely to have a higher body mass index (Redline et al., 1994) and a lower mean income (Scharf et al., 2004). Analysis performed between Asians and whites found that OSA in Asians was significantly more severe compared to whites (Ong and Clerk, 1998). However, differences in age, gender, body mass index, or neck circumference did not account for these differences. Economic Impact of Narcolepsy The impact of narcolepsy on the economy is also not well understood. A review of the PubMed database through May of 2005 found only one relevant report. It examined narcolepsy’s effect on 75 individuals in Germany (Dodel et al., 2004). After converting to American dollars the annual total costs to an individual were $15,410. The average direct costs accounted for 21 percent of the total expenditures ($3,310 total), $1,260 for hospital care, and $1,060 for medications. However, these figures have been extrapolated from a single German cohort and differences in the organization of their respective health care systems have not been taken into account. Therefore, improved surveillance data are needed to determine the actual economic impact of narcolepsy on the American population. The socioeconomic status of an individual does not affect the prevalence and severity of narcolepsy; however, narcolepsy may worsen an individual’s socioeconomic standing. In Germany individuals with narcolepsy have a significantly higher unemployment rate than average, 59 percent compared to the national average of 9 percent (Dodel et al., 2004). Similarly, studies performed in the United Kingdom (Daniels et al., 2001) and the United States (Goswami, 1998) found that 30 to 37 percent of respondents had lost their job due to narcolepsy. Summary Although the data are limited, the effect of sleep disorders, chronic sleep loss, and sleepiness on accident rates, performance deficits, and health care utilization on the American economy is significant. The high estimated costs to society of leaving the most prevalent sleep disorders untreated are far more than the costs that would be incurred by delivering adequate treatment. Hundreds of billions of dollars are spent and/or lost annually as a result of poor or limited sleep. However, greater surveillance and analysis are required to estimate the full economic implications of these problems.
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