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Public health implications of sleep loss: the community burden

Sleep is a basic and necessary biological process that demands to be satisfied as much as our need for food and drink. Inadequate sleep can occur if insufficient time is allowed for it or if a disorder is present that disturbs sleep quality. It is only recently that we have begun to understand the scale of the health and social consequences of insufficient sleep and sleep disorders. Sleep loss from these problems is associated with disturbances in cognitive and psychomotor function including mood, thinking, concentration, memory, learning, vigilance and reaction times.1,2 These disturbances have adverse effects on wellbeing, productivity and safety. Insufficient sleep is a direct contributor to injury and death from motor vehicle and workplace accidents.3 Further, relationships have been demonstrated between shortened sleep and a range of health problems including hypertension,4 type 2 diabetes,5 obesity,6 cardiovascular disease7,8 and total mortality risk.9 Specific sleep disorders such as insomnia,10 obstructive sleep apnoea (OSA)11 and restless leg syndrome12 have also been associated with increased morbidity and mortality. These sleep-related problems incur financial costs relating to health and other expenditures and non-financial costs relating to loss of quality of life. This article considers the prevalence and economic impacts of sleep problems in Australia.

Prevalence of sleep problems

There have been very few studies of the prevalence of disturbed sleep in Australia. A small survey (n = 216) of sleeping difficulties, daytime sleepiness and hypnotic medication use was conducted in Adelaide more than 20 years ago.13 A larger survey (n = 535) was conducted in Newcastle, New South Wales, in 1996 but was limited to a question about insomnia and hypnotic medications.14 Another small survey (n = 267) in rural Victoria among Australian day workers was heavily weighted to men.15 More recently, a large NSW mail survey (n = 3300) reported that 18.4% of participants slept less than 6.5 hours a night and 11.7% complained of chronic sleepiness.16 A recent study of the insomnia burden suggested a prevalence of 5.6%, with increased use of health care.17

To further characterise sleep quality in a large representative sample of Australians, in 2010, the Sleep Health Foundation (www.sleephealthfoundation.org.au) commissioned a national survey of sleeping difficulties and negative daytime consequences of poor sleep. It was modelled on the Sleep in America surveys conducted by the National Sleep Foundation, in part to allow international comparisons. A national polling organisation (Roy Morgan Research) was commissioned to perform the work. It conducted a national landline telephone survey of adolescents and adults (14 to > 70 years of age) across successive weekend evenings. The survey contained 14 questions about sleep: five about sleeping difficulty, two about snoring and OSA, one about restless legs, one about sleeping medication, three about daytime impairments usually associated with sleep disturbance, and two about nocturnal sleep duration (weekdays and weekends) (Box 1). There were 1512 respondents from all states and territories, both urban and rural, with sampling proportionate to the populations of those areas, sex and age.

Box 1 shows the proportions of respondents reporting current sleep difficulties and daytime impairments at least a few times per week (indicative of significant problem), as well as average self-reported sleep duration for the population overall, for males and females, and for each age group. The results illustrate that a considerable proportion of Australians report frequent sleeping difficulties. Overall, 20% of respondents had frequent difficulty falling asleep, which was more prevalent among females and younger age groups. Frequent waking during the night was reported by 35% overall, again more commonly among females but increasing with age. Thirty-five per cent reported waking unrefreshed and 24% reported inadequate sleep. Daytime sleepiness, fatigue/exhaustion and irritability were common issues (19%–24%).

Symptoms were examined to determine likely prevalence of insomnia by selecting those with specific self-reported sleep difficulties plus daytime impairment18 to derive a score that very closely simulates the Insomnia Severity Index, a highly reliable and valid tool to identify clinical insomnia.19 This suggested an overall presence of severe insomnia (Insomnia Severity Index, > 14) of 6.9%, 8.7% in women and 5% in men (Box 1).

Prevalence of sleep apnoea was derived by determining the proportion of respondents who snored loudly at least a few times a week and had observed breathing pauses during sleep at least a few times a month. An overall prevalence of 4.9% was noted, but in this case, prevalence was higher among males (6.4%) than females (3.6%).

While these prevalences of specific sleep disorders were derived from combinations of questionnaire responses, they are similar to the prevalences determined from other population-based studies.10,20 These findings suggest that specific sleep disorders may account for about half of the complaints of daytime sleepiness and fatigue and exhaustion noted in our survey. While other health problems can disturb sleep, particularly in older patients, much of the balance may be due to insufficient sleep duration by choice or through circumstances that result in sleep being given a lower priority than work, social or family activities. Sleep duration estimates are significantly below the putative average adolescent sleep requirement of 9 hours a night and adult sleep requirement of 7.5–8 hours a night for both men and women, particularly among those between the ages of 35 and 65 years.21 Insufficient sleep at least a few times a week was reported by 23.7% of the sample, more frequently by females, and more commonly in the younger to middle-aged groups. Perhaps relevant to this, a study of young adults has shown that those with shorter habitual sleep patterns carried the highest sleep debt, suggesting self-selected sleep restriction.22

The general point that emerges from these data is that inadequate sleep (duration or quality) and its daytime consequences are widely prevalent in Australians, either because of a specific sleep-related disorder or from voluntarily shortened sleep through choice or circumstance. Although there are limitations with telephone surveys (eg, low response rates to landline phone calls), the results are very comparable with those observed in similar surveys conducted elsewhere, such as the 2008 Centers for Disease Control and Prevention study, which reported that 28% of United States adults had insufficient sleep or rest (< 7 h/night) on most nights over a 30-day survey period.23

Economic impact

Poor sleep and its consequences result in significant costs to the community. Although there have been no detailed economic evaluations of the costs associated with insufficient sleep in otherwise healthy individuals, analyses have been undertaken for those with sleep disorders.24,25 OSA provides an example of a widely prevalent sleep disorder with significant comorbidities, including impaired daytime alertness, increased accident risk, hypertension, vascular disease and depression.20 The associated costs include the direct care-related health costs of the sleep disorder itself and the costs of medical conditions occurring as a result of them. In addition, there are substantial indirect financial and non-financial costs. Other financial costs include the non-health costs of work-related injuries, motor vehicle accidents and productivity losses — all common consequences of insufficient sleep. Non-financial costs derive from loss of quality of life and premature death.24

In 2011, the Sleep Health Foundation commissioned Deloitte Access Economics, a national economics consultancy with a strong health economics background, to undertake an analysis of the direct and indirect costs associated with sleep disorders for the 2010 calendar year.25 The methods used were similar to those that they had used in a previous evaluation.24 Such an analysis requires robust data relating to the prevalence of the sleep disorder under consideration, the prevalences and costs associated with conditions with which it has a causal relationship, and the risk ratios describing the strength of these relationships. Using these data, the proportion of each condition attributable to the sleep disorder (the attributable fraction) can be derived. Specifying the prevalences and odds ratios used to calculate attributable fractions imparts transparency to the assumptions involved in calculating them. The fraction can then be used to derive the share of the costs associated with that condition that is attributable to the particular sleep disorder under consideration. Using these methods, Deloitte Access Economics examined costs associated with the three most common sleep disorders — OSA, primary insomnia and restless legs syndrome — as the robust data required for analysis were available.25 It estimated total health care costs of $818 million per year for these conditions, comprising $274 million for the costs of caring for the disorders themselves and $544 million for conditions associated with them. Of these costs, $657 million per year related to OSA: $248 million for OSA itself and $409 million for the health costs of conditions attributable to OSA. These conditions include hypertension, vascular disease, depression, and motor vehicle and workplace accidents. The analysis suggested that 10.1% of depression, 5.3% of stroke, 4.5% of workplace injuries and 4.3% of motor vehicle accidents are attributable to a sleep disorder.

The indirect financial and non-financial costs associated with sleep disorders are much greater than the direct costs. The indirect financial costs were estimated to be $4.3 billion in 2010. These included $3.1 billion in lost productivity and $650 million in informal care and other indirect costs resulting from motor vehicle and workplace accidents. Of these indirect costs, OSA accounted for 61% ($2.6 billion), primary insomnia for 36% ($1.5 billion) and restless leg syndrome for 3% ($115 million).

The report also estimated the effect of sleep disorders on loss of quality of life in terms of disability-adjusted life-years. These costs were calculated using the proportion of total national health costs attributable to sleep disorders to proxy the proportionality of the total national disease burden attributable to these problems. A dollar cost was calculated from the product of these years lost (190 000) and the value of a statistical life-year ($165 000). This added a further non-financial cost of $31.4 billion to the total economic cost of sleep disorders (Box 2). The non-financial nature of this cost gave it less tangibility than financial costs, but the calculation does draw attention to the substantial burden associated with the loss of quality of life resulting from sleep disorders.

As large as they are, these costs are likely to significantly underestimate the total cost to the community of sleep-related problems. Deloitte Access Economics evaluated costs associated with common sleep disorders. The costs of accidents and illnesses associated with sleep loss resulting from poor sleep habits from personal choice and/or from conflicting priorities such as work, social or family activities were not considered as they are difficult to estimate. Further, the analysis used conservative estimates of the prevalence of sleep disorders. For example, the base prevalence of OSA used was 4.7%, which is below the proportion of moderate OSA observed in many contemporary studies, a proportion which is likely to increase further as the population ages and becomes more obese.20 The prevalence of insomnia used in the analysis was also low at 3%, a figure based on primary insomnia estimates.26 Secondary insomnias resulting from other causes were not considered. Our own estimate including all insomnia from a representative Australian sample (Box 1) was closer to 7%. Potential comorbidities of sleep disorders, even if reasonable evidence for an association existed (such as metabolic disorders in the case of OSA), were also excluded from consideration. Finally, the analysis did not cost some aspects of the known comorbidities of sleep disorders, such as the impact of presenteeism (being present at work but operating suboptimally) on productivity and safety. The reason for this omission was the difficulty in reliably quantifying its effects.

Conclusion

Poor or inadequate sleep is very common among Australian adolescents and adults, affecting over 20% on a daily or near-daily basis. Epidemiological studies suggest about half of this problem can be attributable to common sleep disorders such as OSA and insomnia, as together they affect about 10% of the community. The balance appears likely to be the result of inadequate sleep arising from other health problems or issues such as poor sleep habits or sleep loss because of competing demands on time from work, social or family activities. Economic estimates demonstrate that sleep disorders are associated with large financial and non-financial costs. Given that the greatest financial costs appear to be non-medical costs related to loss of productivity and accident risk, it is likely that inclusion of the effects of sleep restriction from poor sleep habits or choice could add considerably to these already substantial amounts.

1 Proportions of survey respondents experiencing sleep difficulties, sleep disorder symptoms and daytime impairments a few times a week or more (often), overall and by sex and age group

Sex


Age group


Difficulty experienced often

Overall

Male

Female

14–17 years

18–24 years

25–34 years

35–49 years

50–64 years

≥ 65 years


Weighted proportion of total

100%

49.4%

50.6%

6.4%

11.7%

17.4%

26.0%

21.9%

16.5%

Sleeping difficulty

Difficulty falling asleep

19.6%

16.9%

22.4%*

33.6%

32.2%

17.6%

20.0%

14.6%

13.5%

Waking a lot during night

34.9%

30.4%

39.3%

21.2%

28.1%

32.6%

42.6%

31.8%

39.5%

Waking up too early

25.3%

22.9%

27.7%*

19.5%

23.4%

20.3%

29.1%*

25.5%

27.9%*

Waking feeling unrefreshed

34.7%

31.8%

37.6%*

38.1%

44.0%

42.0%

39.8%

28.5%

19.3%

Did not get adequate sleep

23.7%

17.9%

29.4%

24.9%

29.3%

25.3%

24.5%

21.4%

19.3%

Snoring, obstructed breathing

Frequent or loud snoring

21.2%

26.4%

12.1%

8.4%

8.6%

21.7%

23.5%

20.0%

20.0%

Pauses in breathing in sleep

6.6%

6.2%

5.1%

2.9%

4.4%

3.8%

4.6%

7.8%*

8.4%*

Restless legs

9.4%

8.6%

10.3%

4.0%

5.3%

11.2%

7.2%

10.7%

14.5%

Prescribed sleep medication use

3.6%

4.0%

3.1%

3.5%

2.5%

1.8%

2.4%

5.8%

5.4%

Daytime symptoms

Daytime sleepiness

19.0%

15.7%

22.3%*

24.6%

26.2%

21.1%

22.4%

13.6%

11.4%

Fatigue or exhaustion

23.5%

20.0%

27.0%

22.8%

27.7%

27.7%

29.1%

18.8%

14.2%

Irritable or moody

18.8%

18.2%

19.3%

18.8%

19.2%

27.9%

22.9%

12.9%

9.8%

Sleep duration

Weeknights (Sunday–Thursday), h

7.16

7.15

7.17

8.24

7.49*

7.18

6.86

7.01

7.14*

Weekend nights (Friday, Saturday), h

7.37

7.37

7.37

8.45

7.37

7.54

7.19

7.29

7.14

Overall, h

7.22

7.21

7.23

8.30

7.46*

7.28

6.95

7.09

7.14*

Sleep disorder estimates

Severe clinical insomnia§

6.9%

5.0%

8.7%*

2.0%

11.3%*

4.2%

10.1%*

6.9%

3.8%

Sleep apnoea,

4.9%

6.3%*

3.6%

0

2.2%

2.1%

4.7%

7.7%*

7.0%*


* P < 0.05. P < 0.001. Adjusted for the 10%–11% who “can’t say”. § Estimated Insomnia Severity Index > 14, derived from data for sleeping difficulty and daytime symptoms. Estimates derived from data for frequent breathing pauses and loud snoring.

2 Summary of the annual costs of sleep disorders and associated conditions, 201021

Variable

AUD (million)


Direct health care cost

Sleep disorders

274

Associated conditions*

544

Indirect financial cost

Productivity

3132

Informal care for accident victims

129

Other cost of motor vehicle accidents

465

Other cost of workplace accidents

53

Deadweight loss to taxation system

472

Total financial cost

5069

Non-financial cost

Loss of disability-adjusted life-years

31 350

Total economic cost

36 419


* Hypertension, vascular disease, depression, motor vehicle injuries and workplace injuries.

Sleep loss and sleep disorders

Shedding light on common but under-recognised individual and community problems

By the time the average person reaches his or her average life expectancy of around 80 years, they will have invested 28 years of their lives in sleep. It is remarkable that an activity of this scale is so taken for granted. Ironically, it is the defining characteristic of sleep — perceptual disengagement from the environment — that may provide the explanation for our disinclination to give our need for sleep its due attention. There is a natural tendency to invest effort in activities that provide conscious reward, and sleep risks being assigned a low priority compared with activities that occur during wakefulness. Importantly, these wakeful activities suffer where sleep is impaired.

While there are numerous hypotheses regarding the precise purpose of sleep, much of what we understand comes from experimental and naturalistic studies of individuals who are subjected to, or subject themselves to, inadequate sleep. Chronic sleep deficiency is believed to be widespread in Western societies.1 Sleep deficiency adversely affects alertness, cognition, productivity, safety, learning and mood and is implicated in a raft of additional pathophysiological processes, leading to adverse metabolic, cardiovascular and mental health outcomes, and premature death. This demands programs to improve sleep habits of the community generally and to detect and treat sleep disorders where they exist.

Linking sleep loss to specific adverse physiological and psychological consequences has led to some important, although limited, instances of behavioural change at the community level. Useful examples can be found in safety-critical industries, where alertness failure can have significant and potentially catastrophic consequences. Transport, aviation and, to some extent, health care industries have attempted to improve rostering practices to allow adequate opportunity for sleep and to minimise disruption of endogenous circadian pacemaker sleep–wake cycles. The duty to provide a safe work environment through enlightened roster arrangements rests with the employer. Equally importantly, employees should act on opportunities for sleep afforded by these rostering systems to ensure that they are “fit for duty”. Although as much as 16% of the Australian workforce is employed in shift work, optimal rostering systems and evidence-based countermeasures for workplace sleepiness are not always readily available or implemented. Despite some progress, the consequences of sleep loss remain under-recognised across the majority of workplaces and much of the community. The direct relationships between healthy sleep and a healthier, more productive and safer community needs to be better understood.

The previous Labor government in Australia identified productivity and population health and wellbeing as strategic research priorities, and as being among the most important challenges facing Australia (http://www.innovation.gov.au/research/Documents/SRP_fact_sheet_WEB.PDF). Good sleep health is a core consideration in both these domains. However, there remains insufficient awareness at leadership level of the importance of optimal sleep in achieving these national goals. The issue of sleep health is yet to be addressed in our national preventive health strategy. Diet and exercise are regarded as key components of a healthy lifestyle, yet despite compelling evidence, minimal attention has been given to healthy sleep. Sleep medicine and sleep science, which are relatively new fields, have much to do to deliver this message to community leaders.

As much as improvement is required in existing practices, sleep health is also confronted by new and emerging challenges. Communities are faced with a rate of technological advancement that is historically unprecedented. The extent to which technology intrudes on our sleep routines remains incompletely defined. However, current observational evidence implicates electronic entertainment and communication devices in sleep loss, academic underachievement and obesity among adolescents.2 Further, late night exposure to the light that is emitted from these devices may disrupt the circadian pacemaker, compounding the sleep disturbance and potential health consequences. There is an urgent need to better educate adolescents and their parents about optimal sleep routines. Schools could be powerful allies in this effort.

As much as unhealthy sleep habits are pervasive in modern society, it is critical that the discipline of sleep medicine ensures that community efforts are focused on effective and cost-effective solutions. Sustainability of any health care program is best secured by establishing goals of care, defining desired outcomes and identifying high-risk groups requiring particular attention. Careful guidance is required to ensure that health care expenditure delivers on preset objectives. Such investment is likely to be richly rewarded through increases in productivity and improvements in safety alone.3 However, blank cheques are never an option, and meeting the challenge of improving sleep health will need to be done within a tight, but not self-defeating, fiscal framework. For example, given that we recognise that continuous positive airway pressure (CPAP) is a cost-effective therapy for higher-risk and symptomatic obstructive sleep apnoea sufferers, strategies for better targeting care delivery to these groups may allow for much needed and consistent CPAP-funding models across the states and territories.

There is much information already in place to inform practice. For example, guidelines are available on appropriate use of therapeutic devices such as CPAP machines.4 However, dissemination of this equipment is unregulated, with the Therapeutic Goods Administration yet to adopt the United States Food and Drug Administration principle of sale of CPAP devices by medical prescription. Guidelines have been recently updated for sleep studies in adults (http://www.sleep.org.au/information/sleep-documents) — an area of potential confusion with the increased availability of diagnostic tools of varying quality in the primary care setting. Accreditation standards among sleep health delivery services, including home and in-laboratory sleep-testing facilities, have led to the evolution an increasingly sophisticated array of benchmarks. These include a recent partnership between the National Association of Testing Authorities and the Australasian Sleep Association to ensure high standards in sleep medicine services (http://www.nata.com.au; http://www.sleep.org.au/information/sleep-documents). Balancing the principle of optimal standards against accessibility, affordability and viability of services is particularly challenging in Australia, with its unique regional and remote demographics.

The articles in this supplement summarise the current understanding of a range of highly prevalent sleep problems and their impact on individual and community wellbeing. Key learning points from the articles can be found in the Box. The articles outline the burden of common sleep problems and their substantial economic cost in the Australian community. Key bodies such as the Sleep Health Foundation and the Australasian Sleep Association play an important role in articulating these issues to the broader health profession, schools, industry, policymakers and society generally to ensure healthy sleep becomes more of an established community priority. This supplement is an expression of their intent to do so.

Sleep loss and sleep disorders: key points

Public health implications of sleep loss: the community burden (page S7)

  • An evaluation of the sleep habits of Australians demonstrates that disrupted sleep, inadequate sleep duration, daytime fatigue, excessive sleepiness and irritability are highly prevalent (20%–35%). While about half of these problems are attributable to specific sleep disorders, the balance appears largely due to poor sleep habits or choices to limit sleep opportunity.

  • The economic impact of sleep disorders includes costs to Australia of $5.1 billion per year of which $800 million are direct health care costs of the disorders and of other medical conditions attributable to them, with the balance of $4.3 billion mainly attributable to productivity losses and non-health costs of sleep loss-related accidents.

Common sleep disorders affecting individuals and communities

Obstructive sleep apnoea:

  • Obstructive sleep apnoea (OSA) is one of the most common sleep disorders. Population studies using sleep recordings show that OSA affects about 25% of adult males and 10% of adult females although most affected individuals do not complain of daytime sleepiness. Combining simple screening questionnaires with home sleep studies is helpful in identifying the severe and symptomatic cases that are likely to benefit most from treatment. Using simplified pathways in controlled studies has shown that patients with a high pretest probability of symptomatic OSA can be managed well in primary care, or by skilled nurses with appropriate specialist sleep service clinical support (page S21)).

  • Severe OSA is strongly associated with increased mortality, stroke and cardiovascular disease in middle-aged populations. The cardiovascular risk from moderate OSA is uncertain, although the data suggest an increased risk for stroke (particularly in men). There is no evidence of increased cardiovascular risk from mild OSA (page S27).

Shift work disorder (page S11):

  • Nearly 1.5 million Australians are employed in shift work. Health, performance and safety are often degraded in shift workers due to the combined effects of circadian rhythm misalignment and inadequate and poor-quality sleep (resulting from disorders such as OSA, insomnia and shift work disorder).

  • Optimal rostering, scheduled napping, appropriately timed light and melatonin treatment to promote circadian adaptation, and judicious use of pharmacotherapy are strategies that aim to mitigate the adverse effects of shift work, along with screening for sleep and mood disorders, and close monitoring of risk factors for cardiovascular disease.

Insomnia (page S36):

  • Insomnia is a very common disorder, with Australian population surveys showing that 13%–33% of the adult population have regular difficulty either getting to sleep or staying asleep. Chronic insomnia is unlikely to spontaneously remit and, over time, will be characterised by cycles of relapse and remission or persistent symptoms.

  • Chronic insomnia is best managed using non-drug strategies such as cognitive behaviour therapy, which can be highly effective. However, if patients have ongoing symptoms there may be a role for adjunctive use of medication such as hypnotics, observing recognised techniques that minimise tolerance and dependency.

Delayed sleep phase disorder (page S16):

  • Delayed sleep phase disorder is a circadian rhythm sleep disorder most commonly seen in adolescents. It needs to be differentiated from insomnia — the use of sleep diaries illustrating delayed sleep onset and waking with normal sleep duration, without imposed restriction, confirms the distinction.

  • Imposing conventional wake times fails to resolve the phase delay and risks sleep loss and the potential for adverse impact on academic performance and social functioning.

  • Awareness and education are important components of the treatment plan. The effects of delayed sleep phase disorder may be minimised by a combination of behavioural and chronotherapeutic strategies. Bright light and melatonin can manipulate the circadian phase; however, their timing in relation to the natural sleep phase is critical to success and sometimes requires specialist input.

Sleep disorders in children (page S31):

  • Sleep disorders are very common in childhood. They include insufficient sleep, frequent night awakenings and OSA.

  • OSA in childhood has important implications for learning, behaviour and cardiovascular health.

  • Adenotonsillectomy can be a highly efficacious therapy for paediatric OSA. However, in 20% of patients, the disease persists despite surgery, particularly among children with obesity, underlying syndromes or malformations.

Circadian rhythm disorders among adolescents: assessment and treatment options

Lethargics are to be laid in the light, and exposed to the rays of the sun for the disease is gloom.

Aretaeus of Cappadocia, celebrated Greek physician, 1st century CE

Circadian rhythm and the biological clock

Biologically, the timing and duration of sleep are regulated by two interacting systems — the homoeostatic sleep drive (process S) and the circadian system (process C).1 Process S assumes that the longer one stays awake, the more pressure there is to fall asleep. Once asleep, this pressure dissipates until a homoeostatic equilibrium is achieved. Process C regulates the timing of sleep by controlling periods of biological activity and inactivity throughout the day. These peaks and troughs in biological functioning are known as circadian rhythms and run for slightly longer than 24 hours in humans.2 Circadian rhythms are generated by the central nervous system pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), sometimes called the body clock. The SCN regulates the rhythmicity of many biological processes, such as temperature and hormone release, and is responsible for synchronising these processes to each other and to the external environment.3 For all terrestrial vertebrates, evening light phase delays and morning light phase advances the biological clock. This daily resetting is how the SCN is synchronised to the 24-hour light–dark cycle and to a multitude of internal rhythms at the level of organs, tissues, cells and genes. In regard to the sleep–wake cycle, the SCN uses external cues such as light, activity and food intake (in some species) to synchronise the timing of sleep to the 24-hour cycle of the social environment. Misalignment between the circadian system and the external environment, where sleep occurs outside societal norms, leads to a circadian rhythm sleep disorder. Only delayed sleep phase disorder (DSPD) and advanced sleep phase disorder are discussed in this article; other circadian rhythm sleep disorders are described elsewhere.4

Common circadian rhythm sleep disorders

DSPD is commonly found in teenagers and young adults (average age of onset, 20 years), with the pattern developing in adolescence.4,5 Sleep onset is delayed by 3–6 hours compared with conventional times (10–11 pm).6 Once sleep is attained, it is normal in length and quality but is delayed, resulting in social and often psychological difficulties. DSPD develops due to an interaction of a delay in the intrinsic circadian rhythm and poor sleep hygiene (staying up increasingly late and often using social networking).

Non-24-hour sleep–wake syndrome (also known as free-running disorder) is where the circadian clock loses synchrony to the day–night cycle and free runs, with sleep onset and wake times occurring progressively later each day. Social and environmental time cues are essentially ineffective and the pattern temporarily moves in and out of phase with societal norms. Sleep onset times may be shifted by 7 hours or more across a week. DSPD is uncommon in the general population but is found in people who are visually impaired, former rotating shift workers and some chronic fatigue/fibromyalgia sufferers.

Advanced sleep phase disorder is uncommon in adolescence, although it may manifest secondary to anxiety and depression. Sleep onset occurs early in the evening (7–9 pm), despite efforts to achieve a later bedtime. Sleep quality is typically normal but duration is often curtailed as a result of early morning waking (2–5 am). Staying in bed until the desired waking time will fragment sleep and may be misdiagnosed as irregular sleep–wake pattern.

Presentation of DSPD

DSPD is relatively common in adolescents and young adults, with a prevalence of 7%–16%, and represents 10% of individuals diagnosed with chronic insomnia disorder in sleep clinics.4 Individuals with DSPD may have an extended circadian cycle of 24.75 hours or longer.3 The major sleep period is therefore delayed, with wake times set intractably late, leading to a propensity to fall asleep later and get up later until there is relative pattern.

When forced to be out of bed at conventional wake-up times, adolescents with DSPD continually experience a short sleep duration and feel permanently jetlagged. This may mask the true nature of the problem, resulting in a diagnosis of psychophysiological insomnia (PPI; also known as sleep-onset insomnia) rather than a circadian rhythm sleep disorder. Adolescents may present to a general practitioner with a history of taking “hours” to get to sleep and being extremely difficult to wake in the morning for school, university or work. They are usually accompanied by a very frustrated parent who may also describe himself or herself as a “night owl”. Exploring family history is important. Adolescents may be withdrawn, indicating an underlying depression often comorbid with DSPD.7 Anxiety symptoms may also be present. The refusal to go to bed when the rest of the family do may be misinterpreted as an adolescent behavioural issue and not a genuine sleep problem. Misunderstandings from both perspectives will negatively impact on family dynamics.

An interaction between PPI and DSPD is not uncommon in adolescence, often stemming from unrealistic parental expectations. Expecting adolescents to fall asleep immediately after being mentally active with homework in the bedroom is unrealistic. The bed in that room has become a psychological reinforcement associated with heightened mental arousal and not sleeping. Time spent on the computer in the bedroom late in the evening playing video games and social messaging has a potentially similar outcome.8

Research indicates that mean optimal daytime alertness in adolescents requires a 9-hour sleep.9 This is rarely achieved, with most students cumulatively sleep-deprived as school weekdays progress,10 negatively impacting on academic performance and psychological health,11 with the added potential of motor vehicle accidents in teenage drivers.12 Restoring the correct timing, enabling sleep for daytime functioning and safety, is paramount.

Treatment of DSPD

There is a paucity of studies examining treatment of DSPD. Few have examined combinations of treatments, and some have focused only on the effects of manipulating sleep timing in healthy sleepers.13,14

DSPD may be treated by:

  • a chronotherapeutic regimen: changing the timing of sleep onset to progressively delay (send forward) sleep onset until it matches a more conventional time;

  • photic factors: bright light therapy;

  • chronobiotic administration: use of a phase-shifter such as melatonin;

  • non-photic factors and healthy sleep parameters: timing of exercise; diet; limiting the use of social media; improving mood.

Tips for assessing and treating DSPD in adolescents are provided in Box 1.

Chronotherapeutic regimen

A raster plot (a graphic representation of sleep–wake patterns) or actigraphy (using a device resembling a wristwatch, which measures movement via an accelerometer to infer sleep/wakefulness from rest/activity cycles) are essential for recording sleep patterns over time.16 Once the current delayed sleep times are established, sleep/bedtime is progressively delayed (moved later and later), usually by 3 hours every 2 days or longer, until sleep onset time moves around the clock to reach the desired bedtime (around 10–11.30 pm).6 Exposure to post-sleep morning light (natural or artificial or a combination) is used to anchor sleep phase to the new, desired time. Sleep and temperature need to be in tandem to maintain this new desired sleep time (Box 2). This is a difficult treatment to implement, as it requires considerable planning, time away from usual daytime activities, specialist input and considerable family support.

Bright light therapy

For the whole of the animal kingdom, irrespective of whether the species is nocturnally or diurnally active, evening light exposure delays the clock while morning light phase advances it. Bright light therapy for DSPD must always be given after the core temperature minimum, which occurs 2–3 hours before wake-up time (Box 2). The body clock is then reset every day. At certain latitudes and seasons, natural exposure to dawn/dusk sunlight is not available and bright artificial light can be substituted to maintain a normal circadian phase. Bright light therapy at the appropriate post-sleep phase drives the sleeping times earlier, back to the desired bedtime (Box 3, B). Light intensity, spectrum, duration and distance from the source are crucial variables. Studies have shown the light intensity required to successfully advance the circadian phase is typically between 2500 and 10 000 lux.17 However, when bright light therapy is used in combination with another therapy, such as cognitive behaviour therapy, as little as 1000 lux exposure is successful.18 Retinal cells in the lower part of the eye sending information to the SCN are tuned to the blue-green end of the spectrum, and this wavelength appears more efficacious than full-spectrum lighting.19

Melatonin

A chronobiotic is a chemical substance capable of therapeutically re-entraining short-term dissociated or long-term desynchronised circadian rhythms, or prophylactically preventing disruption following environmental insult.20 Melatonin is the most researched chronobiotic in terrestrial non-seasonal breeding vertebrates. Human endogenous melatonin levels start to rise about 2 hours before natural sleep onset and peak about 5 hours later (Box 2).

About 40% of overnight core temperature decline during natural sleep is caused by the endogenous release of melatonin, which increases peripheral temperature.19,21 Time of day of melatonin administration is the critical variable with dose being second. Melatonin is administered at the reverse time of day to bright light therapy; ie, evening melatonin advances the sleep–wake cycle while evening light delays it (Box 3, A).

It is important to distinguish between the use of melatonin as a soporific (a weak hypnotic) for PPI15 and its use as a chronobiotic for treating DSPD. In the treatment of PPI, exogenous melatonin administration works best when taken 2 hours before the desired bedtime. When taken for DSPD, it may need to be administered 4–6 hours before the current sleep onset time and be moved progressively earlier as sleep onset moves earlier.22 A soporific effect may occur in the very early evening, with potential driving-safety consequences.

A combination of morning bright light therapy (after core temperature minimum) and evening melatonin can be an ideal treatment regimen. Compared with chronotherapy alone, this approach is more practical and manageable, owing to its shorter implementation period (10–20 days).13

Melatonin: safety issues

Despite assurance from studies,23 there are concerns recommending administration of high doses of melatonin. Circulating endogenous melatonin levels are very high in childhood and decline precipitously at puberty, hence melatonin was speculated but not substantiated to be the pubertal hormone.24 The importance of this rapid natural decline of endogenous levels in early adolescence is unknown, and supplementing high dosages of exogenous melatonin has not been systematically researched. Although the liver is very efficient in clearing circulating levels of melatonin, with a half-life of 45–60 minutes (Box 4), a small dose of 0.3–0.5 mg was found to be as effective as 3 mg for advancing sleep onset.22,25 In the absence of data, the lowest effective dose of 1 mg is recommended (compounding pharmacies).

Where sleep onset is 2 am, we suggest that melatonin be given, for example, at 8.30 pm (ie, 5.5 hours before) for four to five nights, at 8 pm for four to five nights, then slowly working back (7.30 pm, 7 pm, 6.30 pm) until an earlier, desired sleep onset time of 11 pm–12 am is achieved. Once this sleep onset time is established, the individual can be maintained on 0.5 mg of melatonin 2 hours before expected sleep onset (eg, 9.30–10 pm), which will then enhance the natural rise in the melatonin curve. The current prescribing norm of 3 mg (effective for jet lag in adults) and 9 mg doses needs more research and is not recommended for adolescents. Parental supervision is needed to ensure adherence.

Prolonged-release melatonin is thought to mimic the natural endogenous release profile, phase-advance sleep and improve sleep-maintenance insomnia when used as treatment for primary insomnia in older people (> 55 years).26 Research has found the 2 mg melatonin dose subjectively improved sleep quality and morning and evening alertness in that population.26 Anecdotally, it has been used in children and adolescents; however, until there are more research data it would be prudent not to use this medication in adolescents.

Agomelatine, currently marketed as an antidepressant, is a melatonin analogue with phase-advancing properties in rodents (as S 20098)27 and humans.28 Theoretically, agomelatine may be beneficial in older adolescents who have DSPD plus depression, since circadian changes can be associated with major depression.7 It is not the absolute delay in sleep but changes to the phase angle (timing) of sleep relative to other internal changes (onset of endogenous melatonin release relative to sleep phase) that appear crucial in the onset of depression.

Non-photic and extrinsic factors

DSPD can be exacerbated by extrinsic factors, such as use of social media (ie, electronic devices), diet, timing of exercise, and depression and anxiety. Good sleep habits or sleep hygiene are behavioural practices that result in good sleep quality and sufficient sleep duration, and prevent daytime sleepiness.29

Limiting use of technology in the bedroom, particularly in the hour before desired sleep time

The alerting effect of media is strongest when light is predominantly emitted within a blue spectrum.30 Watching television, texting and using a computer or electronic tablet device are associated with delayed sleep onset and poorer sleep quality.8,31,32

Establishing regular sleep patterns

Adolescents tend to sleep longer on weekends to compensate for sleep deprivation incurred over the week. If a catch-up sleep of 1–2 hours (9 am) is required, it is better for this to occur on a Saturday morning. Sunday morning get-up time needs to be 8 am, a mid point between Saturday sleep in time and the necessary Monday morning get-up time of 7 am. Some health professionals advocate adjusting the get-up time to include weekends but we believe a balance between resetting sleep and repaying sleep debt is important.

Caffeine and energy-dense foods before desired
sleep time

Caffeine is a stimulant. The standard measure of one cup of espresso coffee (85 mg caffeine) can last 4 hours after consumption and longer.33 Energy-dense foods, such as those high in sugar content, stimulate the digestive and endocrine system, producing an alerting effect.

Exercise too close to sleep time

In general, regular exercise is a good way to promote sleep and good health. Exercise can delay sleep in young adults if undertaken at usual sleep onset time, and prolonged aerobic exercise even a few hours earlier can maintain high body temperature, increasing alertness and interfering with evening “wind down”.34

Treatment for depression and anxiety

Depression is common in DSPD. If symptoms of depression are present or develop later, it is imperative to treat to reduce exacerbation or a reduction in treatment response to DSPD.7 Sleep anxiety is commonly associated with long periods of lying in bed waiting for sleep onset in DSPD.

Conclusion

DSPD is a circadian rhythm sleep disorder that is most commonly seen in adolescents and needs to be differentiated from insomnia. Sleep diaries or actigraphy illustrating consistently delayed sleep onset and waking with normal (when unrestricted) sleep duration confirm the diagnosis. Many individuals with DSPD feel permanently jetlagged, which impacts on academic performance and has safety ramifications. Awareness and education are important components of the treatment plan, with care being taken to identify the core body temperature minimum. Without this, the effects of DSPD will be exacerbated and the individual is unlikely to respond to treatment. A combination of chronotherapeutic strategies (bright light therapy and melatonin) and behavioural management appears to be the most effective treatment.

1 Tips for assessing and treating delayed sleep phase disorder (DSPD) in adolescents presenting with severe sleep onset insomnia

  • Establish the patient’s full family history — ask about sleep onset difficulties in other family members

  • Establish whether there is a history of sleep onset difficulties as a child/adolescent. Is there a history of napping after school and difficulty getting up for school in the morning?

  • Establish a DSPD diagnosis based on a 2-week diary in the form of a raster plot or actigraphy

  • Refer the patient to a sleep clinic with circadian rhythm specialists where possible

  • Refer to a good reference manual — eg, Wirz-Justice et al15

  • Consider a chronotherapeutic regimen for school holidays if there is considerable family support

  • Establish possible core temperature minimum (2–2.5 h before most usual getting up time)
  • Encourage light exposure (outside or artificial light for at least 40 min) after the minimum core temperature time
  • Consider carefully timed administration of a low dose of melatonin at 1 mg 4–6 hours before prescribed bedtimes
  • Once desired sleep onset time is established, maintain a dose of 0.5 mg of melatonin 2 h before expected sleep onset Have realistic expectations — an individual successfully treated for DSPD is still likely to prefer a later sleep onset time

2 Relationship between endogenous melatonin release,
24-hour sleep–wake cycle and core temperature

DLMO = dim light melatonin onset. M+ = melatonin onset. M2 = melatonin off. Tmax = core temperature maximum. Tmin = core temperature minimum. A. Optimal sleep onset for 7 h total sleep time (TST) is well down the descending limb of the core temperature rhythm and wake up time about 2–2.5 h after Tmin. B. For an 8 h TST, natural wake-up time would be about 3 h after Tmin. DLMO occurs about 2 h before sleep onset and 40% of the fall in core temperature is due to melatonin release. From the perspective of a teenager with a “normal” melatonin profile, there is no reason to expect that exogenous melatonin administration can drop core temperature any lower and thereby increase TST (in contrast to older people with low melatonin, reduced circadian amplitude and often fragmented sleep).

3 Phase–response curve in relation to melatonin administration and light exposure, along with how to instigate bright light therapy

A. Phase–response curve in a normally entrained individual for melatonin (3 mg) administration over 3 consecutive days compared with bright light. Evening light phase delays the human clock while morning light phase advances. Early evening melatonin phase advances the clock while morning administration modestly delays phase. Source: Barion and Zee;13 redrawn with permission. Original data derived from Littner et al16 and Gooley.17 B. Schematic diagram of “morning” bright light therapy in a delayed sleep phase disorder patient with sleep onset at about 0300 h and natural wake-up time at 1100 h. Full-spectrum bright light exposure is moved earlier and earlier every 2 days (in this example) until the target bedtime is achieved. The decision on how often to advance light exposure is made from the advancing sleep onsets recorded daily in raster plots. If pre-sleep melatonin is administered to achieve a similar result, it would be taken earlier and earlier as sleep onset advances over successive days.

4 Natural and exogenous melatonin profiles

A. Endogenous plasma melatonin profile (pg/mL) of an adult male. Source: Norman TR, Armstrong SM; unpublished data, 1986; redrawn with permission. B. Plasma melatonin profile (ng/mL) of another adult male after ingestion of 5 mg melatonin capsule during daytime hours. Note the efficient clearing of circulating melatonin by the liver within
a 40 min window, but despite this efficiency, the persistence of aphysiological levels (1300 pg) 4 hours postingestion. Source: Short and Armstrong;20 redrawn with permission.

Insomnia: prevalence, consequences and effective treatment

Insomnia is a very common disorder that has significant long-term health consequences. Australian population surveys have shown that 13%–33% of the adult population have regular difficulty either getting to sleep or staying asleep.1,2 Insomnia can occur as a primary disorder or, more commonly, it can be comorbid with other physical or mental disorders. Around 50% of patients with depression have comorbid insomnia, and depression and sleep disturbance are, respectively, the first and third most common psychological reasons for patient encounters in general practice.3 Insomnia doubles the risk of future development of depression, and insomnia symptoms together with shortened sleep are associated with hypertension.4,5

Insomnia is defined in the fifth edition of the Diagnostic and statistical manual of mental disorders (DSM-5) as difficulty getting to sleep, staying asleep or having non-restorative sleep despite having adequate opportunity for sleep, together with associated impairment of daytime functioning, with symptoms being present for at least 4 weeks.6 Having a sleep experience that does not meet our expectation, such as with some transient awakenings but with good daytime functioning, does not constitute insomnia.

Acute versus chronic insomnia

Acute insomnia is defined as sleep disturbance meeting the DSM-5 definition of insomnia, but with symptoms occurring for less than 4 weeks.6 Generally, acute insomnia is triggered by precipitating events such as ill health, change of medication or circumstances, or stress. Once the precipitating event passes, sleep settles back to its usual pattern. Hence, treatment for acute insomnia is focused on avoiding or withdrawing the precipitant, if possible, and supporting the acute distress of not sleeping with short-term use of hypnotics if symptoms are significant. This is the usual approach in primary care, with 95% of general practitioner consultations for insomnia resulting in the prescription of a hypnotic, usually a benzodiazepine.7

However, if patients have repeated episodes of acute insomnia or ongoing comorbidities, insomnia symptoms can persist and evolve into chronic insomnia, which requires a different treatment approach. Once people have had difficulty sleeping for over 4 weeks, they have usually begun to behave and think about sleep differently, in ways that are maladaptive and perpetuate their sleep difficulties.8 The long-term course is then generally one of relapse and remission rather than resolution,9 which continues well after the acute precipitating circumstances have passed. Therefore, the treatment approach needs to match this, with a chronic disease management model educating and upskilling patients on how best to manage their insomnia symptoms over time. Health care providers need to see insomnia as a chronic illness and emphasise the role of strategies to prevent relapses, rather than focusing on treatment of acute episodes or crises.

Assessment and diagnosis of insomnia

The assessment and diagnosis of insomnia is formulated mainly from a systematic sleep history. To assist in establishing premorbid baseline sleeping patterns and formulating treatment goals, clinicians must ask patients about their typical sleeping pattern before they developed insomnia.

Insomnia assessment involves understanding the patient’s typical sleep pattern at night and over a time frame of weeks to months. Therefore, part of the sleep assessment is asking for the patient’s narrative of typical bedtime, time taken to fall asleep after lights out (sleep latency), frequency and rough duration of awakenings in the middle of the night, and what time the patient gets out of bed. Are there times when sleep returns to normal? Was there an initial trigger or did the symptom arise spontaneously? Was it related to a period of stress, anxiety or depression? Did it start during childhood and continue thereafter? Are there lifestyle factors contributing to insomnia, such as too much caffeine or exercise late in the day, television or pets in the bedroom, or use of alcohol or nicotine? Knowing the patient’s cognitions, beliefs and worries about sleep, which are often apparent in the language and emotion used when they describe their sleep, can assist in the formulation of specific behavioural and calming approaches to assist with sleep.

It is important to assess the effects of poor sleep on the patient. Common daytime consequences include mood lowering, irritability, poor memory, fatigue, lack of energy and general malaise. These can manifest as work absenteeism, with insomnia being one of its leading medical causes.10 It is also imperative to ask for risky consequences of insomnia, including accidents and sleepiness while driving.

Identifying the body clock type of the patient is crucial in excluding circadian rhythm disorders. A commonly undiagnosed condition, delayed sleep phase disorder is a body clock variation where the patient is biologically inclined to go to sleep much later than usual (typically after midnight), yet generally sleeps well after sleep onset, with a natural wake time that is much later than for most people and is often incompatible with normal school or work start times.

It is also important to look for comorbid conditions that can present with insomnia, such as depression and anxiety, chronic medical conditions, and other sleep disorders. Comorbid conditions have a bidirectional relationship with insomnia, with each influencing or exacerbating the other and requiring concurrent assessment and management. The Auckland Sleep Questionnaire, a validated sleep screening questionnaire in primary care, is one tool that can assist in identifying these disorders.11 Other validated questionnaires such as the Insomnia Severity Index can help to document the severity of patients’ symptoms and assess their response to treatment.12

Since many people with insomnia overestimate their sleep disruption and underestimate actual sleep time, a 2-week sleep diary is a very helpful assessment tool as it assists the sleep clinician to get a more accurate snapshot of sleep compared with a pure verbal account.13 For some, a sleep diary is revealing in that they realise that they do get some sleep, albeit fragmented or superficial. This can provide the basis for discussion. There are several downloadable sleep diaries online — for example, http://yoursleep.aasmnet.org/pdf/sleepdiary.pdf. If patients have difficulty completing a sleep diary, or there is significant misperception of sleep suspected, actigraphy (using a device worn on the wrist to monitor sleep–wake cycles) can be used to objectively measure sleep.

Although an overnight sleep study or polysomnography is not routinely indicated in diagnosing insomnia, it can be helpful in diagnosing several conditions, including obstructive sleep apnoea, sleep-related movement disorders, parasomnias, or insomnias that are treatment-resistant.13 A routine physical and mental status examination can give clues regarding comorbid medical and or mental health conditions. Other tests including laboratory and radiographic procedures are not routinely indicated in chronic insomnia.13

Non-pharmacological treatment of insomnia

Cognitive behaviour therapy aimed at treating insomnia (CBT-i) targets maladaptive behaviour and thoughts that may have developed during insomnia or have contributed to its development. CBT-i is considered to be the gold standard in treating insomnia, with effect sizes similar to or greater than those seen with hypnotic drugs and, unlike with hypnotics, maintenance of effect after cessation of therapy.14,15 These effects are seen in both primary and comorbid insomnia.16

The implementation of individual face-to-face CBT-i is typically delivered by a trained health professional, which makes it expensive, labour intensive and therefore beyond the reach of many. Patients with insomnia are eligible for Medicare rebates for psychological treatment if they are referred under the Chronic Disease Management or Better Access to Mental Health Care initiatives. Telephone and online delivery of CBT-i have been shown in clinical trials to be as effective as face-to-face CBT-i.17,18 While these different treatment delivery models have the potential to markedly improve access to CBT-i, they need to be investigated further with respect to their long-term reliability and effectiveness. They might be best used as part of a stepped-care approach.19 Some patients may need little guidance, while others may need more personal treatment and guidance.

CBT-i consists of five major components: stimulus control, sleep restriction (also known as sleep consolidation or bed restriction), relaxation techniques, cognitive therapy and sleep hygiene education (Box 1). Typically, CBT-i is delivered in four to 10 sessions, either individually or in a group setting, ideally involving four to eight participants.

Stimulus control is a reconditioning treatment forcing discrimination between daytime and sleeping environments.20 For the poor sleeper, the bedroom triggers associations with being awake and aroused. Treatment involves removing all stimuli that are potentially sleep-incompatible (reading, watching television and use of computers) and excluding sleep from living areas. The individual is instructed to get up if he or she is not asleep within 15–20 minutes, or when wakeful during the night or experiencing increasing distress, and not return to bed until feeling sleepy.

Sleep restriction relates to better matching the time spent in bed to the average nightly sleep duration.21 Patients keep a sleep diary to determine average sleep duration. They are then allowed a period of time in bed equal to this plus 30 minutes, and set a regular arising time. As some patients can underperceive the amount of sleep, the time in bed should never be set at less than 5 hours. As sleep becomes more consolidated, the length of time in bed can be gradually increased in 15–30 minute increments. This effective intervention induces natural sleepiness (reduced time in bed) and gives the individual a sense of assurance that bed is now a safe place to sleep. Bed restriction has recently been shown to be an effective intervention in primary care.22

Relaxation techniques include progressive relaxation, imagery training, biofeedback, meditation, hypnosis and autogenic training, with little evidence to indicate superiority for any one approach. Patients are encouraged to practice relaxation techniques throughout the day and early evening. Even a few minutes two to four times a day is useful. A last-minute relaxation attempt minutes before sleep will not work miracles. Muscular tension and cognitive arousal (eg, a “chattering” mind) are incompatible with sleep. At the cognitive level, these techniques may act by distraction. Relaxation reduces physical and mental arousal but is less effective as a stand-alone treatment and is better used in combination with other treatment interventions.

Cognitive therapy involves enabling the patient to recognise how unhelpful and negative thinking about sleep increases physiological and psychological arousal levels. Setting aside 15–20 minutes in the early part of the evening to write down any worries, make plans for the following day and address any concerns that might arise during the night allows the day to be put to rest. It is helpful to challenge thoughts that arise at night with “I have already addressed this and now I can let go of it!”. “Time out” — some form of soothing activity before bed — can be useful in reducing arousal levels. Thought-stopping attempts or blocking techniques, such as repeating the word “the” every 3 seconds, occupy the short-term memory store (used in processing information), potentially allowing sleep to happen. Cognitive restructuring challenges unhelpful beliefs, such as “if I don’t get enough sleep tonight, tomorrow is going to be a disaster”, which maintain both wakefulness and helplessness. Another cognitive and behavioural technique is paradoxical intention. Clients are encouraged to put the effort into remaining wakeful rather than trying to fall asleep (decatastrophising), thereby strengthening the sleep drive and reducing performance effort.14

There is limited evidence to suggest that, on its own, sleep hygiene is efficacious.14 However, it is an essential component of CBT-i and involves “cleaning up” or improving an individual’s sleep environment and behaviour to promote better sleep quality and duration.23

Mindfulness and insomnia

In recent years, the technique of mindfulness has become increasingly popular and is likely to be efficacious in helping to promote sleep by reducing cognitive and physiological arousal. Mindfulness treatment interventions have demonstrated statistically and clinically significant improvements in several night-time symptoms of insomnia, as well as reductions in presleep arousal, sleep effort and dysfunctional sleep-related cognitions.24 In many cases, mindfulness is combined with CBT-i.24,25 As an adjunct to CBT-i, it can be used for psychoeducation to help the client develop a more functional schematic model of sleep and for dealing with sleeplessness, including the detrimental role of hyperarousal. Typically, the chattering mind is focused on past or future events, whereas mindfulness emphasises being non-judgemental in the present, which potentially can reduce mind activation.

Bright light exposure (natural or artificial)

Educating the patient about sleep and the importance of bright light is an important aspect of treating insomnia. Good objective information about sleep, sleep loss and the body clock are helpful starting points for self-management. Bright light is a potent synchroniser for human circadian rhythm. In particular, morning light, which can be combined with exercise such as walking, can be helpful in consolidating night-time sleep and reducing morning sleep inertia.26

Pharmacological treatment of insomnia

Although psychological and behavioural interventions are indispensable and effective for most insomnia sufferers, some will still need the extra help from pharmacological agents. Current medications and natural products used for insomnia include benzodiazepine-receptor agonists, melatonin and variants, antidepressants, antipsychotics and antihistamines.

Hypnotic drugs that act on the γ-aminobutyric acid receptor include benzodiazepines, such as temazepam, as well as the benzodiazepine-receptor agonists, such as zopiclone and zolpidem. Medications of this group have been studied in randomised controlled trials, with efficacy over 6 months27 and longer in open-label extensions.28 Many doctors avoid prescribing medications from this family, mainly because of concern regarding dependence and tolerance. However, long-term trials of eszopiclone (not available in Australia) and extended-release zolpidem have shown sustained response with no tolerance and dependence after 6 months of daily use.2729 Despite these findings, the concern remains that there are vulnerable patients who may become dependent on hypnotic drugs. To limit the risk of tolerance and dependence, the prescriber can instruct the patient to use the medication on a scheduled basis; for example, only on alternating nights, or three times a week and at the lowest effective dose possible for a limited time (ie, a month).27 Zolpidem has been associated with parasomnias, so clinicians need to warn patients about unusual sleep behaviours as a side effect. Sudden discontinuation of this class of medications can result in a rebound insomnia that can be mitigated by a gradual taper.

Despite the similarity in the mode of action and pharmacokinetics of these agents, patients react differently to each product. Lack of response to one agent does not mean that others of the same group will not work. Similarly, an adverse effect of one does not mean that others will cause the same reaction. The decision whether or not to prescribe hypnotics should rely on a careful risk–benefit analysis by both the doctor and the patient. In addition to the perceived risk of dependence and tolerance, clinicians should consider the risks of untreated insomnia.

Melatonin has been shown to be effective in treating insomnia, particularly among people aged over 55 years.30 However, melatonin is more effective as a chronobiotic for treating body clock conditions like jetlag and delayed sleep phase disorder than as a treatment for chronic insomnia.31

Sedating antidepressants (eg, doxepin, amitriptyline, mirtazapine, trimipramine), sedating antipsychotics (eg, quetiapine, olanzapine) and antihistamines are used off-label as sleep medications, despite insufficient evidence.13,32,33 Many clinicians prefer prescribing these medications over hypnotics, because of perceived concerns regarding the risks of dependence and tolerance associated with hypnotics, and despite antidepressants, antipsychotics and antihistamines also having serious side effects including weight gain, anticholinergic side effects and diabetes. The decision to prescribe this group of medications for insomnia should be based on a careful risk–benefit analysis, not solely on concerns regarding the risks associated with hypnotics.

Among herbal and alternative medication choices for treating insomnia, valerian has the most evidence showing possible mild improvements in sleep latency, with inconsistent effects on the rest of the objective sleep parameters.13 Although valerian shows some promise in improving sleep latency without side effects, the clinical trials are poorly designed and generally of short duration.34

Conclusion

Insomnia is complex and usually chronic by the time the individual consults a health practitioner, with cognitive, behavioural and social factors involved in its maintenance. Simple instructions, such as avoiding stress, or short-term use of hypnotics are usually not effective. CBT-i is an effective intervention with long-term efficacy that enables patients to better manage and live with their insomnia symptoms. The development of online delivery of CBT-i markedly improves access to treatment and can be readily used in primary care as first-line treatment for most patients, with specialised sleep services managing more complex cases, those with ongoing symptoms and those who require person-to-person care.

1 Cognitive behaviour therapy for insomnia

Intervention

General description

Specific instructions


Stimulus control

BED = SLEEP. Set of instructions aimed at conditioning the patient to expect that bed is for sleeping and not other stimulating activities. Only exception is sexual activity. Aim is to promote a positive association between bedroom environment and sleepiness

Go to bed only when sleepy/comfortable and intending to fall asleep. If unable to sleep within what feels like 15–20 minutes (without watching the clock), leave the bed and bedroom and go to another room and do non-stimulating activity. Return to bed only when comfortable enough to sleep again. Do not read, watch television, talk on phone, pay bills, use electronic social media, worry or plan activities in bed

Sleep-restriction therapy

Increases sleep drive and reduces time in bed lying awake. Limits the time in bed to match the patient’s average reported actual sleep time. Slowly allows more time in bed as sleep improves

Set strict bedtime and rising schedule, limited to average expected hours of sleep reported in the average night. Increase time in bed by 15–30 minutes when the time spent asleep is at least 85% of the allowed time in bed. Keep a fixed wake time, regardless of actual sleep duration

Relaxation techniques

Various breathing techniques, visual imagery, meditation

Practise progressive muscle relaxation (at least daily). Take shorter relaxation periods (2 minutes) a number of times per day. Use breathing and self-hypnosis techniques

Cognitive therapy

Identifies and targets beliefs that may be interfering with adherence to stimulus control and sleep restriction. Uses mindfulness to alter approach to sleep

Unhelpful beliefs can include overestimation of hours of sleep required each night to maintain health; overestimation of the power of sleeping tablets; underestimation of actual sleep obtained; fear of stimulus control or sleep restriction for fear of missing the time when sleep will come

Sleep hygiene education

Emphasises environmental factors, physiological factors, behaviour, habits that promote sound sleep

Avoid long naps in daytime — short naps (less than half an hour) are acceptable. Exercise regularly. Maintain regular sleep–wake schedule 7 days per week (particularly wake times). Avoid stimulants (caffeine and nicotine). Limit alcohol intake, especially before bed. Avoid visual access to clock when in bed. Keep bedroom dark, quiet, clean and comfortable

Sleep disorders in children

Sleep problems, including problems at bedtime and frequent night waking, affect 30%–40% of infants and children before school age.1 Effects of sleep disorders on the health of the child may include poor growth, adverse behavioural and learning effects and, for the child and family, worsened mental health, and poor quality of life.2 The likelihood that important and treatable sleep disorders go unrecognised is increased because many parents do not mention their concerns to their general practitioner, or the doctor does not ask about or identify the issues.3,4 Simple management strategies can be effective at a primary care level. An important role of the GP or general paediatrician is to identify children’s sleep problems and to differentiate those who would benefit from referral to specialty services.

Average sleep times vary with age, and community surveys indicate considerable variability in sleep requirements, to the extent that normative values are sometimes debated. However, systematic review of the literature can guide general recommendations for sleep duration at different ages.5 Newborn infants sleep 16–18 hours per day in cycles of 3–4 hours (day and night). After 6 months of age, healthy infants can sleep for more than 6 hours at night without a feed. By 18 months of age, sleep patterns usually mature to overnight sleep plus one daytime nap. By school age, sleep consolidates into a single night sleep of 11–12 hours. Sleep duration continues to slowly reduce from about 10 hours in prepubescent children to 8 hours by 16 years of age. Individual children and adolescents may benefit from longer sleep times than these average figures, and enquiry about daytime functioning is an important part of assessing adequacy of sleep.5,6

Initial screening is an important aspect of identifying sleep issues in children and the first step in providing timely advice and intervention. An example of a mnemonic to remind physicians of important aspects of history-taking regarding sleep quality in children is BEARS: B = bedtime (settling) problems; E = excessive daytime sleepiness; A = night awakenings; R = regularity and duration of sleep; S = snoring.7 Parents define the presence of children’s sleep problems, so evaluation of the validity of parental expectations is also important. Age-specific common non-respiratory sleep problems are tabulated in Box 1.8

Non-respiratory disorders

Sleep phenomena or parasomnias in children

Parasomnias are undesirable motor, autonomic or experiential phenomena that occur exclusively or predominantly during sleep.9 Parasomnias are common in childhood — examples include bruxism (teeth grinding, 6%–10%), sleep terrors (0.7%–2%) and somnambulism (sleep walking, up to 7%).10 A simplified summary of parasomnias with their prevalence rates is provided in Box 2.8 Benign parasomnias may run in families, increase in frequency with any condition that causes sleep deprivation or sleep fragmentation such as fever, and tend to improve with age (Box 2).8

Behavioural sleep disorders

Extremely common sleep problems in children include a child not getting into bed, having difficulty or requiring undue help to settle to sleep, frequent waking in the night and/or getting out of bed, and very early morning awakenings. They are often grouped as behavioural sleep disorders because of the perception that the problem lies with how the child behaves. These problems may lead to insufficient sleep and considerable family disruption. Children with developmental disorders, attention deficit hyperactivity disorder, depression and anxiety have higher incidence of these types of sleep disturbances than other children.11

Management of behavioural sleep disorders and parasomnias

Key to reducing the frequency and severity of behavioural sleep disorders is the provision to parents of preventive information, best provided opportunistically in primary care and by maternal child health nurses. Treatment interventions should then be evidence-based and developmentally appropriate. Parasomnias are usually benign and most decrease in frequency in later childhood. Education and reassurance of parents may be all that is required in less severe cases. Behavioural strategies for management of parasomnias include anxiety-relaxation techniques for poor sleep initiation, and sleep hygiene measures.11 These include limit-setting — for example, gradually removing parents’ attendance at the child’s bedside, so they are not present at the time of sleep onset — and moving bedtime closer to the usual time of sleep onset, to avoid periods of lying in bed awake before sleep onset. These measures help to eliminate the need for parents to attend to the child at each night-time awakening, and encourage a pattern of prompt sleep onset after going to bed. Together, they avoid prolonged periods of wakefulness during the night.

The core principle of preventing and managing bedtime (settling) issues and frequent night waking is to promote independence in settling to sleep. Infants and children who depend on a parent or other sleep association (music, dummy, rocking) at the start of the night are likely to require the same attention to resume sleep after what are otherwise normal, brief awakenings during the night. Consistency is the most important factor, but the rate of possible change is family-specific and sometimes needs to occur in slow, small steps to be sustained. Maternal mental health is an important factor in managing paediatric sleep disorders; children’s sleep problems and poor maternal sleep can contribute to mental health disorders, as well as being an aetiological factor for the inconsistent maintenance of the infant’s sleep routines. In a small group of toddlers with difficulty initiating or maintaining sleep, melatonin could be used to entrain their sleep routine. The interventions are also safe, with no negative long-term outcomes and many benefits to child and family health and functioning.12

Parasomnias can occur very frequently, cause distress and/or disrupt family life. Management strategies should ensure the safety of the child; for example, by placing the mattress on the floor rather than on a bed frame, and by adding locks to doors to prevent the child opening simple latches while sleep walking. Simple strategies to minimise the frequency of events are often effective for managing parasomnias in otherwise normal children and include:

Extending sleep: insufficient sleep increases the frequency of parasomnias. As little as 30 minutes of additional sleep can reduce the frequency of parasomnias. Work towards earlier bedtime and/or later rise times. Making bedtime earlier should occur in small steps of 10–15 minutes, to avoid increasing bedtime struggles.

Reducing bedtime anxiety and struggles/conflict: going to bed in an aroused state (anxious, angry or upset) can intensify parasomnias. Aim for a gentle and predictable bedtime routine. Avoid stimulating activities like television or computer games for an hour before bed. If necessary, match bedtime to the usual sleep onset time (even if this is late), then slowly bring bedtime earlier, as above. Medication is rarely indicated.11,13 If the problem is very severe, very frequent or atypical, raising the possibility of a seizure disorder, then referral to a sleep specialist is indicated, with polysomnography and/or electroencephalography indicated depending on the clinical scenario.

Investigating excessive daytime sleepiness and circadian rhythm disorders: excessive sleepiness requires systematic evaluation. Possible causes include inadequate sleep, sleep disruption from conditions such as restless leg syndrome and obstructive sleep apnoea (OSA), and circadian rhythm disorders. In children with an apparently sufficient duration of sleep, marked daytime sleepiness may be the only manifestation of narcolepsy, which has an estimated prevalence of 1 in 4000 to 1 in 2000, and a peak of onset at 14 years of age.14 Recognition of narcolepsy onset in childhood and appropriate treatment is likely to improve learning and daytime functioning.

Disruption to normal circadian rhythmicity, such as very late bed and rise times, can have substantial effects on the ability of a child to participate in school and other activities. Circadian sleep problems are especially common in children with pervasive developmental disorders such as autism spectrum disorder, and also occur in adolescents, where many factors impact on a tendency for the sleep phase to be delayed into the night, making socially imperative morning rise times difficult to achieve. The main focus of therapy is to establish and maintain good sleep hygiene including settling strategies (eg, avoiding screen time and caffeine-containing drinks before bedtime) and consistent timing of sleep throughout the 7-day week. Specialist referral is advised if there is concern about accuracy of diagnosis, or need for additional medical therapy including use of medications such as melatonin. Use of such medications may be indicated but must be in the context of awareness of the high need for ongoing surveillance of short- and long-term side effects.

Respiratory disorders

Snoring and OSA

Snoring and OSA are common, affecting 3%–15% of children, with peak prevalence in the preschool years when lymphoid tissue size in the upper airway is largest relative to the size of the facial skeleton.15 OSA affects up to 5.7% of children,16 and so potentially affects one child in every classroom in the country. Although the highest incidence of OSA is in preschoolers (3–5 years of age) with large tonsils, 9% prevalence of snoring has been documented in infants aged 0–3 months.15,17

Identification of severe OSA is important because it is linked to increased risk for postoperative respiratory compromise, including emergency reintubation and unplanned admissions to intensive care. It is a major challenge to identify the children who require perioperative management in tertiary paediatric centres. Box 3 highlights cases where referral for polysomnography is warranted, rather than direct referral for adenotonsillectomy.

OSA is associated with sleep fragmentation and repeated episodes of hypoxia. Polysomnography is superior to other testing methods for determining disease severity and also permits diagnosis of comorbid disorders (eg, periodic limb movements). The thresholds for severity of OSA are lower than in adults, with OSA defined as ≥ 1 obstructive event per hour of sleep on polysomnography. Treatment is generally recommended if the frequency of obstructive respiratory events is > 1.5 per hour. Severity is usually defined as mild for 1–5 events per hour, moderate for 5–10 events per hour and severe for ≥ 10 events per hour. However, no threshold has been established for disease severity with regard to the development of complications. Even mild disease is associated with adverse neurocognitive, behavioural and cardiovascular outcomes, such that even chronic partial obstruction causing snoring without gas exchange abnormalities or evident sleep disruption is associated with adverse effects.

Despite the fact that no clinical assessment method other than polysomnography has proven discriminatory for OSA in children who snore, the number of paediatric sleep units in Australia is inadequate to provide polysomnography to screen all snoring children. The presence of snoring and large tonsils is a sensitive but not specific marker. Helpful clinical indicators include increased work of breathing, parental concern, and frequent daytime mouth breathing.18 Markers that are specific but not sensitive (helpful when positive, but unable to rule out disease) include excessive daytime somnolence and observed OSA.19 Almost all screening tools are also specific but not sensitive, including overnight oximetry (most useful if positive, but most children have a negative study that does not rule out OSA20), video recordings and nap studies, so the search for an ideal screening tool continues. Overnight oximetry is helpful in identifying cases with marked hypoxia, but those using it need to be familiar with the technical aspects and diagnostic limitations of the tool.21 All screening tools, including oximetry, are best used in combination with clinical indicators such as young age (under 3 years) and comorbidities (syndromes, obesity, etc), to help evaluate the likelihood of postoperative respiratory complications.21

Among the major sequelae of untreated OSA, cardiovascular risks include systemic hypertension, increased sympathetic activation and ventricular hypertrophy, while pulmonary hypertension and right heart failure still occur occasionally in infants and children with severe OSA.22 Even mild OSA is linked to daytime neurocognitive dysfunction that translates into decrements of intelligence quotient, and a randomised controlled study has now been published regarding assessment of neuropsychological development in school-age children with OSA after tonsillectomy.23 Plausible mechanisms for this association include sleep fragmentation, repetitive hypoxia, and reduced cerebral blood flow and oxygenation. Behavioural improvements follow adenotonsillectomy,2426 but responses in neurocognitive function are variable.27 A review of 25 studies investigating behavioural and neurocognitive outcomes following adenotonsillectomy found that all studies reported improvement in one or more measures including quality of life, behavioural problems including hyperactivity and aggression, and neurocognitive skills including memory, attention and school performance.26 Improvement or resolution of OSA has also been linked to concomitant improvements in systemic and pulmonary blood pressures, heart rate and pulse variability, cardiac morphology and cardiac function.22

The natural history of symptoms of OSA (eg, snoring, mouth breathing and apnoea) is for around 50% of preschool children to move (bidirectionally) among severity groups over a 2-year follow-up period.28 In a cohort of 12 447 children studied across seven time points between ages 6 months and 6.75 years, the prevalence of OSA symptoms was highest between 3.5 and 4.8 years of age.29 The highest peak of new symptoms occurred between the ages of 1.5 and 2.5 years.29 Another study undertook polysomnography on 45 children with mild OSA at baseline; at follow-up 4 years later, disease had worsened in 37% and resolved in 26%.30

Preschool children generally respond to adenotonsillectomy; meta-analysis shows cure rates of 82% in otherwise normal children.31 Success rates for adenotonsillectomy are lower in obese32 and older33 children, and adenoidectomy and/or tonsillectomy is usually not appropriate for infants. Although adenotonsillectomy reduces the severity of OSA in obese children, such children have more severe initial disease, and obesity increases the risk for persisting disease.32,34 Nasal corticosteroid sprays3537and leukotriene-receptor antagonists (eg, monteleukast)38 are helpful in children with mild OSA and for some with persistent disease after adenotonsillectomy, and a treatment trial is appropriate before pursuing other interventions.39 Specific airway problems, especially infants with Pierre Robin sequence, may respond to mandibular distraction, continuous positive airway pressure, nasopharyngeal tube, and/or oral tongue positioning devices, but may necessitate tracheostomy.

Factors that indicate a higher risk for persisting OSA despite adenotonsillectomy include more severe initial disease (respiratory disturbance index > 10/h or minimum SaO2 < 80%), obesity with body mass index > 95th percentile for age and sex, and children aged > 7 years at the time of surgery (whether obese or non-obese).33 There is interplay between obesity and atopy, in that for non-obese children, comorbid asthma increases the risk of persisting disease whereas allergic rhinitis is only significant when both obese and non-obese groups are considered together.40 These groups need follow-up after surgery to establish whether snoring has or has not resolved.

Older children and adolescents may respond to adenotonsillectomy or require other treatments including continuous positive airway pressure, orthodontic and other surgical or dental procedures (rapid maxillary expansion, or mid-face advancement). Evidence of efficacy and safety in children is limited for orthodontic options such as mandibular advancement splints.4144 These interventions aim to affect growth of the face and oropharyngeal airway to produce long-term structural changes, irrespective of whether the initial airway problem is primary, or secondary to OSA.

Children with underlying medical disorders

Underlying medical disorders work to both increase risk for OSA and to reduce the effectiveness of surgical treatment (Box 3). In particular, congenital abnormalities that affect craniofacial or thoracic growth, such as achondroplasia and Down syndrome, will predispose to sleep-disordered breathing. In Down syndrome, there appears to be particular risk for hypertrophy of the lingual tonsils.33 It is also known that children with multiple disabilities have increased risk for other sleep disturbances such as difficulties with sleep initiation and maintenance, insomnia and other sleep pattern abnormalities.45

Children with neuromuscular diseases have increased incidence of OSA in the first decade.46 Congenital cardiothoracic abnormalities or restrictive lung disorders, often linked to neuromuscular disorders or neurodevelopmental disability such as cerebral palsy, also predispose to nocturnal respiratory failure. Symptoms suggestive of nocturnal hypoventilation include increased frequency or severity of lower respiratory tract infections, and progression of scoliosis. Screening should include pulmonary function testing, with sleep studies for children with vital capacity < 60% of that predicted and for non-ambulant children before scoliosis surgery, and pragmatic consideration of screening versus full polysomnographic studies.47 Early identification and treatment of impaired pulmonary function can prevent or reduce the frequency and duration of admissions to intensive care units, as well as improving quality and duration of life.48

Congenital central hypoventilation syndrome is a rare but highly treatable condition (incidence, 1 in 50 000 live births).49 This usually presents during the neonatal period with frequent apnoeas or colour change during sleep, but milder forms can present in older children.50

Conclusion

Sleep disorders are common in childhood and are associated with significant consequences for children and parents. Behavioural disorders include sleep onset delay, sleep interruptions, early morning waking and combinations of these elements. Parasomnias are very common and can be frequent and severe enough to warrant specialist referral. Access to tertiary and specialist assessment services is limited, so good triage of sleep disorders by primary care services and general paediatricians is essential. Identification and treatment of OSA is important in children. Immediate risk for respiratory compromise can be identified before adenotonsillectomy, and there are high rates of cure after surgery. Untreated, OSA is associated with risk of cardiovascular, neurodevelopmental and ongoing respiratory health problems. For triage purposes, Box 3 highlights situations where referral for specialist services with access to polysomnography is suggested in cases of suspected OSA. Finally, children with persisting symptoms despite surgery will often benefit from polysomnography and specialist evaluation to determine the severity of ongoing disease, identification of cause, and need (or not) for ongoing treatment. Childhood presents an opportunity for effective, early intervention in sleep disorders.

1 Examples of non-respiratory sleep disorders in childhood, by most common age at presentation8

Age group

Non-respiratory sleep disorder


Infant/toddler (0–2 years)

Behavioural insomnia of childhood: eg, excessive night waking, sleep associations (aids to sleep onset, such as rocking, dummy, milk)

Rhythmic movement disorders: eg, body rocking

Preschool (3–5 years)

Behavioural insomnia of childhood: eg, excessive night waking, bedtime refusal

Rhythmic movement disorders: eg, head banging

Night terrors

Primary school (6–12 years)

Inadequate sleep: eg, due to social pressures such as evening activities and/or poor sleep habits such as watching television in bed

Sleep walking

Adolescent (13–18 years)

Inadequate sleep: eg, due to delayed sleep phase syndrome

Narcolepsy

Periodic limb movements

2 Sleep-state distribution of sleep-related symptoms and parasomnias in childhood that do not require treatment unless they are very frequent or severe*

Sleep state

Diagnosis

Prevalence

Presentation


Non-rapid eye movement-related

Hypnogogic imagery (awake or lucid dreaming)

51%

Vivid visual dreams while in transition to sleep

Sleep starts

33%

Sudden involuntary “jumps” at sleep onset

Confusional arousals

17%

Child appears to wake, often distressed, but does not respond normally

Night terrors

17%

Out of slow-wave sleep, so most often in first third of the night. Child appears to wake and be terrified, but remains unaware of surroundings; attempts to comfort can prolong the event

Sleep walking

14%

Out of slow-wave sleep, so most often in first third of the night. Child performs apparently coordinated activity (walking, opening doors) but electroencephalography and behaviour retain some characteristics of sleep

Rapid eye movement-related

Dreams

na

Semi-coherent images and sensations recalled after sleep

Sleep paralysis

7.6%, general population

Seconds to minutes of being unable to perform voluntary movement at sleep onset or awakening

Nightmare

5.2%, one per week; 10%–50%, 3–5 year olds

Dreams with frightening content

Sleep-state independent

Bruxism

28%

Sounds of grinding and/or evidence of tooth wear

Rhythmic movement disorder

17%

Body rocking or head banging mainly at sleep onset and/or following night awakenings

Sleep talking

55%

Semi-coherent speech while apparently asleep

Periodic limb movements

8.4%–11.9%

Repetitive, brief limb movements during sleep that can cause sleep disturbance, daytime sleepiness and leg discomfort. Associated with reduced iron stores


* The major differential diagnosis of parasomnias, which needs to be excluded in frequent or severe cases, is frontal lobe epilepsy.

3 Indications for polysomnography in a child suspected to have obstructive sleep apnoea (OSA)

Indications


Conditions with increased surgical risk that should have documentation of disease severity

Complex medical conditions such as Down syndrome, neuromuscular disorders and craniofacial syndromes

Age < 3 years

Discordance between history and examination

For example, strong history of OSA with small tonsils and no apparent nasal obstruction

Potential alternative explanations for sleep disturbance

Possible combination of central apnoea/hypoventilation (eg, spina bifida)

Need to differentiate nocturnal epilepsy (eg, from parasomnias)

Persistence of symptoms after adenotonsillectomy

High-risk groups for persisting OSA: severe initial disease; history of prematurity; congenital syndrome/malformation; obesity; atopy; age > 7 years

Mercury poisoning from home gold amalgam extraction

This is the first Australian report of confirmed minimal change disease with nephrotic syndrome, which occurred in a 62-year-old man who inhaled mercury vapour in his home. This case highlights the immediate and delayed effects of such poisoning on multiple organs. Prompt and sometimes prolonged treatment may prevent long-term damage.

Clinical record

A 62-year-old man first presented to his general practitioner complaining of a cough, dyspnoea and lethargy for which he was prescribed oseltamivir phosphate, as his symptoms were presumed to indicate influenza. He re-presented 2 days later with worsening dyspnoea, at which point he revealed a history of mercury exposure. He had attempted to extract gold from an amalgam containing mercury by heating the amalgam in an aluminium pan inside his home. He was exposed for 3 hours — initially, to fumes, and subsequently, through direct skin contact as he attempted to clean up some spilt liquid amalgam. The windows were open and he used a tea towel covering his nose as protection from the fumes. A chest x-ray showed extensive alveolar shadowing consistent with pneumonitis. He was admitted to a regional hospital, and was given supplemental oxygen and antibiotics. His blood mercury level was 5933 nmol/L (level of concern, > 70 nmol/L). On the advice of a toxicologist, he was transferred to a tertiary hospital for chelation therapy.

On arrival at the tertiary hospital, his oxygen saturation on room air was 92% and signs on examination and repeat chest x-ray results were consistent with severe pneumonitis. His other vital signs were stable. Findings of other clinical examinations, including neurological examination, were unremarkable. Laboratory investigations showed he had an increased white cell count of 16.3 × 109/L (reference interval [RI], 4.0–11.0 × 109/L), a platelet count of 617 × 109/L (RI, 150–400 × 109/L), a serum albumin level of 21 g/L (RI, 34–48 g/L), and mild abnormalities in liver function test results (total protein, 60 g/L [RI, 65–85 g/L]; globulin, 39 g/L [RI, 21–41 g/L]; total bilirubin, 15 µmol/L [RI, 2–24 µmol/L); γ-glutamyl transpeptidase, 274 U/L [RI, < 60 U/L]; alkaline phosphatase, 228 U/L [RI, 30–110 U/L]; alanine aminotransaminase, 92 U/L [RI, < 55 U/L]; aspartate aminotransferase, 102 U/L [RI, < 45 U/L]; and lactate dehydrogenase, 294 U/L [RI, 110–230 U/L]). In a spot urine sample, the mercury concentration was 7556 nmol/L and the mercury : creatinine ratio was 2519 nmol/mmol (level of concern, > 5.8 nmol/mmol). Pulmonary function testing was suboptimal owing to the patient’s inability to suppress coughing on inspiration, but the results suggested a restrictive deficit. Analysis of a spot urine sample showed a protein concentration of 60 mg/L (RI, < 150 mg/L) and a protein : creatinine ratio of 18 mg/mmol (RI, < 12 mg/mmol). The patient’s serum creatinine level was 82 µmol/L (RI, 50–120 µmol/L) and his estimated glomerular filtration rate was > 60 mL/min/1.73 m2.

The patient was treated with dimercaptosuccinic acid (DMSA) chelation therapy, 800 mg three times a day for 7 days, after which the dose was reduced to 800 mg twice daily for a further 14 days. He was also treated with prednisolone 50 mg daily, gradually tapering the dose to zero over 3 weeks. Box 1 shows the 24-hour urinary mercury excretion in relation to exposure to mercury vapour, serum albumin concentrations and treatment with chelation therapy.

During this initial hospital stay, the patient’s dyspnoea decreased markedly, and subsequent chest x-rays showed resolution of interstitial shadowing. His liver function test results also normalised, and his serum albumin level rose to 33 g/L. The mild vertigo he had reported, with no other neurological symptoms or deficits, resolved spontaneously.

He was discharged on DMSA 800 mg twice daily and prednisolone 15 mg daily (tapering dose), and it was planned to repeat the assessment of his mercury levels after completion of the initial 3-week course of DMSA. This reassessment showed ongoing elevated levels (blood mercury, 418 nmol/L; urinary mercury, 1019 nmol/24 h), so the patient was rechallenged with DMSA at 800 mg three times a day for 34 days, commencing on Day 66 after exposure. Improved clearance resulted, as evidenced by a subsequent increase in urinary mercury excretion (from 1762 nmol/24 h on Day 62 to a maximum of 5790 nmol/24 h on Day 67). Consequently, treatment with DMSA at 800 mg twice daily was resumed, with the intention of giving a prolonged course, and his blood mercury levels and renal mercury clearance were assessed periodically. His serum albumin level had normalised by this point, and his prednisolone course had been completed.

Approaching 1 month into this prolonged course of DMSA, he re-presented with a history of fatigue, increasing peripheral oedema, nausea and vomiting. Physical examination revealed significant peripheral oedema with intravascular volume depletion. Biochemical analysis showed a serum albumin level of 6 mg/L (nadir, 3 g/L), urinary protein level of 13.4 g/24 h (RI, < 150 mg/24 h), serum creatinine level of 133 µmol/L (peak, 220 µmol/L) and serum cholesterol level of 13 mmol/L, indicating severe nephrotic syndrome. A renal ultrasound scan was unremarkable. In a renal biopsy specimen, light microscopy showed glomeruli of normal appearance and electron microscopy showed podocyte effacement consistent with minimal change disease (Box 2). He was treated with prednisolone, regular infusions of concentrated albumin, and diuretics, and was restricted to 1.2 L of fluids daily. Treatment with an HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor and prophylactic warfarin therapy were also commenced. His nephrotic syndrome abated and renal function gradually normalised over the course of 4 months.

The patient experienced significant nausea, which necessitated cessation of chelation therapy after a total of 7 weeks. At this point, his blood mercury level was 112 nmo/L; within 1 month it fell below the level of concern. Three months after cessation of treatment with DMSA, his urinary mercury level was also normal. When last reviewed, his serum albumin level was 35 g/L and urinary protein excretion was 0.25 g/24 h. Resolution of his respiratory injury was almost complete, without evidence of developing neurotoxicity.

Discussion

We present a case of prolonged exposure to mercury vapour with characteristic “fume fever” illness followed by pneumonitis and nephrotic syndrome, and an associated body mercury burden requiring prolonged chelation therapy.

Heating of mercury forms mercury vapour, which is actively absorbed in the lungs. About 80% of mercury vapour formed from amalgams is absorbed through inhalation.1 Once absorbed, metallic mercury is rapidly oxidised to mercurous and mercuric ions,2 and distributes in a variety of tissues including the brain, kidneys, liver, testes, thyroid gland and oral mucosa. A small amount of elemental mercury remains in the blood and can easily pass through the blood–brain barrier and the placental barrier.

The symptoms and signs of mercury inhalation vary according to the concentration of mercury to which the patient is exposed and the duration of exposure. Acute exposure to high levels primarily causes respiratory symptoms such as dyspnoea, chest pain, tightness, and dry cough, secondary to chemical pneumonitis. Absorption at the alveolar and bronchiolar levels causes capillary damage, pulmonary oedema, and desquamation and proliferation of airway lining cells, leading to the obliteration of air spaces.3 Airway obstruction and capillary leakage may cause alveolar dilatation, pneumothorax and, in severe cases, acute respiratory distress syndrome.4 Systemically, mercurous and mercuric ions can bind with sulfhydryl groups, leading to inactivation of sulfhydryl-containing enzyme systems and structural proteins and alteration of cell-membrane permeability.5

The evolution of clinical symptoms after mercury vapour inhalation may be described in three phases.6 The initial phase is typically an influenza-like illness occurring 1 to 3 days after exposure. The intermediate phase is dominated by severe pulmonary toxicity and may involve renal, hepatic, haematological, and dermatological dysfunction. Our patient had hypoalbuminaemia and a mild and transitory abnormality in liver enzyme levels, followed by a delayed onset of minimal change disease with severe nephrotic syndrome. It is possible that DMSA chelation may have contributed to the nephrotic syndrome by subjecting nephrons to a high load of chelated mercury. Both his initial hypoalbuminaemia and subsequent nephrotic syndrome appeared to respond to steroid therapy. The most commonly reported histological abnormality in the kidney associated with mercury exposure is membranous glomerulopathy;7 however, minimal change disease, with negative findings on light microscopy and confirmed by characteristic findings from immunofluorescence and electron microscopy, has been previously described.8 The late phase is characterised by gingivostomatitis, tremor and erethism, which we have not seen in our patient.

Aggressive supportive care including continuous cardiac monitoring and pulse oximetry, supplemental oxygen therapy and mechanical ventilation4 remains the cornerstone of therapy after acute inhalational mercury poisoning. Several chelating agents bind mercury, increasing its water solubility and augmenting its renal elimination. Historically, dimercaprol, D-penicillamine and N-acetyl-penicillamine have been used.5 Recently, DMSA has proven to be more effective and less toxic. It is unclear to what extent chelation therapy reduces mercury tissue burden or prevents long-term neurological injury.9 Awareness among clinicians of the immediate and the delayed consequences of mercury poisoning, with prompt treatment, may help to avoid long-term organ damage.

1 Twenty-four-hour urinary mercury excretion in relation to exposure to mercury vapour, serum albumin concentrations and treatment with chelation therapy


DMSA = dimercaptosuccinic acid; shading indicates periods of therapy.

2 Micrographs of the patient’s renal biopsy specimen, showing features consistent with minimal change disease


A: Light micrograph showing glomeruli of normal appearance (haematoxylin and eosin stain; original magnification, × 200). B: Electron micrograph showing flattening of podocyte foot processes (arrows).

Should we screen for lung cancer in Australia?

Systematic screening reduces mortality, but is it the best way to go?

Lung cancer is the leading cause of cancer death in Australia. Late diagnosis of advanced disease contributes to the poor 13% 5-year survival rate associated with lung cancer. However, the recently updated United States National Lung Screening Trial (NLST) showed a 20% survival benefit from early detection with low-dose computed tomography (CT) screening.1,2 In light of these results, should people in Australia at high risk of lung cancer now undergo screening?

The NLST randomly allocated 53 000 participants to three rounds of annual screening with either chest CT or chest x-ray, with follow-up for a further 3 years.1,2 Unlike population-based screening programs for other common cancers, the NLST only enrolled high-risk participants (ie, current smokers or former smokers who had quit within the past 15 years, aged between 54 and 74 years, with > 30 pack-years). Adherence to screening was over 90%. At the initial screen, three times more stage 1A tumours (< 3 cm, no metastases) were detected on CT than on chest x-ray; most of these were resected.2 However, the absolute reduction in the risk of death from lung cancer was small (0.33%), with 320 participants being screened annually for 3 years to avoid one lung cancer death over 6 years.1

Harm did occur.3 The cumulative positive scan rate approached 40% over 3 years.1 While it is not directly comparable because of different screening intervals, this rate is several times higher than that in other screening programs, such as the Australian National Bowel Cancer Screening program, where only 7.8% of people screened biennially had a positive result on the screening test (faecal occult blood test).4

In the NSLT, over 95% of positive scans were shown to be false positives — that is, cancer was not present. However, most false positives required only repeat scanning. Invasive investigations were needed in a minority of instances, and the risk of fatal complications was small (0.03% within the CT arm of the study), reflecting the expert care provided to participants at trial centres. Radiation-induced cancer death could not be measured in the 6-year follow-up of the NLST, but is estimated at 0.04% 10–15 years after screening at the relevant levels of radiation exposure.3

Lung cancer screening therefore appears efficacious under optimal conditions and in expert hands. The absolute benefit, however, is modest and may be rapidly eroded by small decrements in effectiveness, or minor increments in harm.3 For example, a doubling of radiation risk (with the use of older scanners) and fatal complications (at inexperienced centres) coupled with a halving of screening effectiveness (by a lack of expert treatment pathways) could completely negate all benefit. Therefore, despite ready access to CT scanners, screening should not be performed sporadically in the absence of a systematic screening infrastructure.

Before Australia can embark on systematic screening, issues of local feasibility must be addressed. Many such questions will be answered by the Queensland Lung Cancer Screening Study, which is now midway through recruitment.5 This study adapted the NLST protocol to an Australian population, and will inform the implementation of future screening.

Cost presents a more formidable challenge. Of the approximately two million individuals in Australia aged between 54 and 74, roughly 400 000 were smokers 15 years ago, and many continue to smoke. Not including infrastructure, the cost of a screening program comprising three annual CT scans (with downstream tests and treatments) was calculated at $16.5 million per 10 000 individuals screened (2002 prices).6 Screening 400 000 individuals over 3 years would therefore cost $660 million. Assuming a screening uptake rate of 75%, annual costs would amount to $165 million.

Is such expenditure cost-effective? Dividing $660 million by an estimated 1250 lives saved gives a cost of $530 487 per death averted. Assuming a sustained benefit from screening, each patient whose death from lung cancer is averted gains 13 life-years.7 Thus the cost per life-year gained is in the region of $40 000, which approaches the cost-effectiveness of biennial bowel screening8 or cervical screening.9

However, there is already a more powerful method to reduce mortality in this high-risk population. Primary prevention is far more effective than screening, by at least an order of magnitude. The direct costs of smoking cessation interventions in 2003 Australian prices were between $1000 and $4000 per successful quitter, depending on the combination of cessation techniques.10 The cost of smoking cessation interventions per life-year gained therefore ranges between $250 and $1000, because smoking cessation adds 4 years of life to each quitter in their early sixties.11 Younger quitters derive even greater benefit.11

Formal up-to-date costings for screening should be undertaken given that available Australian models are a decade old. However, national lung screening is likely to strain health care expenditure, already stretched by expansions to breast and bowel screening programs. While systematic screening would likely save some lives, its running costs may be equivalent to the annual expenditure on all lung cancer care.12

In the United States, alternatives to full government support are being suggested, such as partially or fully self-funded screening, or tobacco-taxation. In Australia, the question for debate is whether screening should be implemented at all, until effectiveness and cost-effectiveness are substantially enhanced. Currently, smoking cessation is far ahead on both counts. Thus, greater emphasis (and more funding) should be directed towards intensified tobacco control and sustained quitting.

For now, in the absence of a coordinated nationwide program, we caution that sporadic lung screening has the potential for harm rather than benefit. We propose instead that smokers should be vigorously directed towards quitting.