N J Douglas

Randomized Controlled Clinical Effectiveness Trial of Cognitive Behavior Therapy Compared With Treatment As Usual for Persistent Insomnia in Patients With Cancer

PURPOSE Persistent insomnia is a common complaint in cancer survivors, but is seldom satisfactorily addressed. The adaptation to cancer care of a validated, cost-effective intervention may offer a practicable solution. The aim of this study was to investigate the clinical effectiveness of protocol-driven cognitive behavior therapy (CBT) for insomnia, delivered by oncology nurses. PATIENTS AND METHODS Randomized, controlled, pragmatic, two-center trial of CBT versus treatment as usual (TAU) in 150 patients (103 females; mean age, 61 years.) who had completed active therapy for breast, prostate, colorectal, or gynecological cancer. The study conformed to CONSORT guidelines. Primary outcomes were sleep diary measures at baseline, post-treatment, and 6-month follow-up. Actigraphic sleep, health-related quality of life (QOL), psychopathology, and fatigue were secondary measures. CBT comprised five, small group sessions across consecutive weeks, after a manualized protocol. TAU represented normal clinical practice; the appropriate control for a clinical effectiveness study. RESULTS CBT was associated with mean reductions in wakefulness of 55 minutes per night compared with no change in TAU. These outcomes were sustained 6 months after treatment. Standardized relative effect sizes were large for complaints of difficulty initiating sleep, waking from sleep during the night, and for sleep efficiency (percentage of time in bed spent asleep). CBT was associated with moderate to large effect sizes for five of seven QOL outcomes, including significant reduction in daytime fatigue. There was no significant interaction effect between any of these outcomes and baseline demographic, clinical, or sleep characteristics. CONCLUSION CBT for insomnia may be both clinically effective and feasible to deliver in real world practice.

A Randomized, Placebo-Controlled Trial of Online Cognitive Behavioral Therapy for Chronic Insomnia Disorder Delivered via an Automated Media-Rich Web Application

STUDY OBJECTIVES The internet provides a pervasive milieu for healthcare delivery. The purpose of this study was to determine the effectiveness of a novel web-based cognitive behavioral therapy (CBT) course delivered by an automated virtual therapist, when compared with a credible placebo; an approach required because web products may be intrinsically engaging, and vulnerable to placebo response. DESIGN Randomized, placebo-controlled trial comprising 3 arms: CBT, imagery relief therapy (IRT: placebo), treatment as usual (TAU). SETTING Online community of participants in the UK. PARTICIPANTS One hundred sixty-four adults (120 F: [mean age 49y (18-78y)] meeting proposed DSM-5 criteria for Insomnia Disorder, randomly assigned to CBT (n = 55; 40 F), IRT placebo (n = 55; 42 F) or TAU (n = 54; 38 F). INTERVENTIONS CBT and IRT each comprised 6 online sessions delivered by an animated personal therapist, with automated web and email support. Participants also had access to a video library/back catalogue of session content and Wikipedia style articles. Online CBT users had access to a moderated social network/community of users. TAU comprised no restrictions on usual care and access to an online sleep diary. MEASUREMENTS AND RESULTS Major assessments at baseline, post-treatment, and at follow-up 8-weeks post-treatment; outcomes appraised by online sleep diaries and clinical status. On the primary endpoint of sleep efficiency (SE; total time asleep expressed as a percentage of the total time spent in bed), online CBT was associated with sustained improvement at post-treatment (+20%) relative to both TAU (+6%; d = 0.95) and IRT (+6%: d = 1.06), and at 8 weeks (+20%) relative to IRT (+7%: d = 1.00) and TAU (+9%: d = 0.69) These findings were mirrored across a range of sleep diary measures. Clinical benefits of CBT were evidenced by modest superiority over placebo on daytime outcomes (d = 0.23-0.37) and by substantial improved sleep-wake functioning on the Sleep Condition Indicator (range of d = 0.77-1.20). Three-quarters of CBT participants (76% [CBT] vs. 29% [IRT] and 18% [TAU]) completed treatment with SE > 80%, more than half (55% [CBT] vs. 17% [IRT] and 8% [TAU]) with SE > 85%, and over one-third (38% [CBT] vs. 6% [IRT] and 0% [TAU]) with SE > 90%; these improvements were largely maintained during follow-up. CONCLUSION CBT delivered using a media-rich web application with automated support and a community forum is effective in improving the sleep and associated daytime functioning of adults with insomnia disorder. CLINICAL TRIAL REGISTRATION ISRCTN - 44615689.

Tumour necrosis factor-α (−308) gene polymorphism in obstructive sleep apnoea–hypopnoea syndrome

Patients with obstructive sleep apnoea–hypopnoea syndrome (OSAHS) have elevated circulating levels of tumour necrosis factor (TNF)-α. The hypothesis in this study was that OSAHS might be associated with the TNF-α (−308A) gene polymorphism, which results in increased TNF-α production. This hypothesis was examined in OSAHS patients, their siblings and population controls. A total of 206 subjects were recruited. All underwent sleep studies and clinical review, and were subsequently classified as having OSAHS or not depending on apnoea–hypopnoea frequency, sex, age and symptoms. All subjects had blood collected and genotyping was performed on DNA extracted from peripheral leukocytes. Some 192 random UK blood donors were used as population controls. The results demonstrated a significant association for TNF-α (−308A) allele carriage with OSAHS (OR = 1.8; 95% Confidence interval: 1.18–2.75) when compared with population controls. Siblings with OSAHS were significantly more likely to carry the TNF-α (−308A) allele. In addition, 21 pairs of male siblings discordant for carriage of the −308A allele showed a significant level of discordance for the OSAHS phenotype. In conclusion, this study demonstrates an association of tumour necrosis factor-α (−308A) carriage with obstructive sleep apnoea–hypopnoea syndrome, suggesting that inflammation may be implicated in the pathogenesis of this condition.

Systematic review of the efficacy of nasal CPAP

Continuous positive airway pressure (CPAP) therapy has been regarded for more than a decade by those in the field as the treatment of choice for the sleep apnoea/hypopnoea syndrome (SAHS). Nevertheless, two recent systematic reviews1 2 have appropriately pointed out that there is a shortage of robust evidence that CPAP benefits medium and long term outcomes in SAHS. However, the striking aspect of the two reviews is their diametrically opposed conclusions about the efficacy of CPAP, one concluding from the evidence that CPAP was indicated in patients with more than 20 apnoeas + hypopnoeas per hour of sleep plus daytime sleepiness,1 whereas the other concluded that “the studies do not provide sufficiently robust evidence for the effectiveness of CPAP”.2 There are differences in the design of these reviews which may account for this disparity. Systematic review should be impartial. The review by Wright and colleagues3 was funded, at least in the initial stages, by purchasing authorities concerned about the increasing costs of provision of sleep services and CPAP. Sackett has commented that there is a “fear that evidence based medicine may be hijacked by purchasers and managers to cut the costs of healthcare”.4 The study by Wright et al 2 would appear to be one such example. In contrast, the Australasian study1 was commissioned by the Australian Medical Research Council and the New Zealand Ministry of Health. Evidence based medicine has been defined as “integrating individual clinical expertise with the best available external clinical evidence from systematic research”, where clinical expertise is “the proficiency and judgement that individual clinicians acquire through clinical experience and clinical practice”.4 Wright and colleagues2 did not …

IRREGULAR BREATHING AND HYPOXAEMIA DURING SLEEP IN CHRONIC STABLE ASTHMA

Breathing patterns, ear oxygen saturation (SaO2), and EEG sleep-stage throughout an undisturbed nights sleep were compared in ten adult stable asthmatics and ten age-matched healthy subjects. The two groups slept equally long (5.0-7.2, mean 6.2 h), but the asthmatics slept less well; they had more periods of wakefulness and drowsiness and irregular breathing than did the healthy subjects. They also had greater and more frequent falls in SaO2. Most hypoxaemic episodes occurred in the rapid-eye movement phase of sleep and were associated with hypopnoea or apnoea, but no patient had a classical sleep-apnoea syndrome. The severity of nocturnal hypoxaemia was related to the level of SaO2 when the subjects were awake, but did not correlate with the fall in forced expiratory volume recorded in eight out of ten asthmatics after sleep.

Self assessment of daytime sleepiness: patient versus partner.

BACKGROUND--Patients with the sleep apnoea/hypopnoea syndrome (SAHS) and their spouses often differ in their assessment of the patients sleepiness. A study was therefore undertaken to investigate whether either the patients or partners rating on the Epworth sleepiness scale (ESS) was better related to illness severity. METHODS--Nocturnal variables (apnoeas+hypopnoeas/hour (AHI) and arousals/hour) and patient and partner ESS scores were compared in 103 new patients attending the sleep clinic. RESULTS--Mean patient and partner ESS scores were not different. In the whole population neither patient nor partner ESS variables correlated with AHI or arousal frequency. In the patients with SAHS (AHI > or = 15), partner ESS correlated weakly with AHI, but patient ESS did not. CONCLUSIONS--This study suggests that neither patient nor partner ESS ratings are strong predictors of SAHS severity.

Tongue protrusion strength and fatiguability: Relationship to apnoea/hypopnoea index and age

The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by retroglossal or retropalatal narrowing. The site of obstruction, and the fact that negative pressure in the upper airway increases retroglossal airway size, suggests that tongue muscles may play a role in the maintenance of upper airway patency. We therefore hypothesized that tongue protrusion strength and fatiguability may be predictors of apnoea/hypopnoea index, vary with age and may be different in SAHS patients and normal subjects. Maximal strength (Fmax) and fatiguability (measured as the total time subjects were able to maintain 50% Fmax on three consecutive occasions separated by 30 s) were assessed using a force transducer in 98 consecutive apnoeic/hypopnoeic male patients referred to our laboratory for sleep studies [apnoea/hypopnoea index (AHI) range 3–130/h, age range 30–74 y]. Fmax and fatiguability were also compared in 15 male SAHS patients (mean AHI 20/h) and 15 nonsnoring male subjects matched for age, body mass index and fat free mass. A further 26 SAHS patients had tongue protrusion strength/fatiguability measured before, during and after a night’s sleep. Log AHI was only weakly correlated with Fmax (r=− 0.21; P=0.03) and age (r=0.23; P=0.025), but not to fatiguability (P > 0.05). Comparison between SAHS and nonsnoring subjects did not demonstrate significant differences in Fmax (P=0.1) or fatiguability (P=0.1). There was no evidence of a change in muscle strength (P > 0.05) or fatigue (P > 0.05) during the course of a night’s sleep. We conclude that tongue protrusion strength and fatiguability are unlikely to be important factors in the pathogenesis of SAHS.

Is nocturnal asthma caused by changes in airway cholinergic activity

A randomised, double blind, placebo controlled crossover trial of high dose nebulised ipratropium was carried out in 10 asthmatic patients with documented nocturnal bronchoconstriction. Patients received nebulised saline or ipratropium 1 mg at 10 pm and 2 am on two nights. Absolute peak flow (PEF) rates were higher throughout the night after the patients had received ipratropium (at 2 am, for example, mean (SEM) PEF was 353 after ipratropium and 285 l/min after placebo). The fall in PEF overnight, however, was similar with ipratropium and placebo. Patients were given a further 1 mg nebulised ipratropium at 6 am on both nights. There was a significant overnight fall in PEF on the ipratropium night even when comparisons were made between the times that maximal cholinergic blockade would be expected, PEF falling between 11.30 pm and 7.30 am from 429 to 369 l/min. The percentage increase in PEF, though not the absolute values, was greater after ipratropium at 6 am than at 10 pm. These results confirm that ipratropium raises PEF throughout the night in asthmatic patients, but suggest that nocturnal bronchoconstriction is not due solely to an increase in airway cholinergic activity at night.

Effect of sustained release terbutaline on symptoms and sleep quality in patients with nocturnal asthma.

The effect of an oral sustained release beta 2 agonist on symptoms, sleep quality, and peak flow rates has been studied in nine patients with nocturnal asthma. Patients received oral terbutaline 7.5 mg twice daily or placebo for seven days in a double blind crossover study and spent the last two nights of each limb in a sleep laboratory. Oral terbutaline improved morning peak flow (259 v 213 l min-1) and decreased nocturnal inhaler usage (1.3 v 1.9) with no alteration in sleep quality as assessed electroencephalographically. The study shows that oral sustained release terbutaline can be useful in the treatment of nocturnal asthma without impairment of sleep quality.

Breathing patterns during sleep in patients with nocturnal asthma.

Breathing patterns early and late in the night, at the same sleep stage, were compared in six healthy subjects and 15 adults with nocturnal asthma, to try to identify changes of overnight bronchoconstriction, and breathing patterns at different sleep stages, to see whether there were changes related to sleep stages that were indicative of bronchoconstriction. Despite an average 31% fall in FEV1 overnight in the patients with asthma, neither breathing frequency nor expiratory time, which might be expected to change during bronchoconstriction, was different early in the night from late in the night, nor did they differ between sleep stages. There was no evidence of asynchronous movement of the chest and abdomen in any patient. This study did not identify any abnormality of breathing pattern that would indicate the development of nocturnal asthma without the need to awaken the patient.