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Chronic low back pain (LBP) shares a bidirectional relationship with sleep disturbance. Analgesics are often used for chronic LBP management however, the effects on sleep have not been thoroughly reviewed. This systematic review and meta-analysis assessed the effect of opioid and non-opioid medications on sleep in people with chronic LBP. Electronic databases were searched for randomized controlled trials which resulted in 16 eligible articles (14 studies). Sleep measures were secondary outcomes, with one study assessing sleep objectively and all other studies reporting subjective sleep. Twelve studies assessed opioid therapies whilst two studies examined non-opioid therapies. Eight studies (all opioid) were included in meta-analyses of sleep quality and sleep disturbance comparing opioid therapies with placebo-controls. Opioid therapies significantly improved sleep quality (SMD = 0.27, 95% CI: 0.17-0.36) and reduced sleep disturbance (SMD = 0.32, 95% CI: 0.25-0.40) compared to placebo-control. These findings show a clear improvement in subjective sleep associated with opioid therapies however, future studies should examine objective sleep outcomes which remain largely unexplored in chronic LBP. Addressing both pain and sleep together is important for effective management of comorbid conditions of chronic LBP and sleep disturbance due to their bidirectional relationship.

Summary The comparative efficacy of various approaches of digital cognitive behavioral therapy for insomnia (CBTi) is still unclear. This network meta-analysis explored the comparative efficacy of digital CBTi approaches in adults with insomnia. Four electronic databases were searched from inception to June 27, 2020. Primary outcomes were self-reported total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE), and insomnia symptoms; these were measured using sleep diaries or valid questionnaires. A random-effects network meta-analysis in a frequentist framework was used. Fifty-four randomized controlled trials comprising 11,815 participants were included. Compared with usual care, web-based CBTi with a therapist demonstrated significantly longer TST (mean difference [MD]: 23.19 min, 95% confidence interval [CI]: 18.98 to 27.39 min), shorter SOL (MD: −18.76 min, 95% CI −24.20 to –13.31 min), lower WASO (MD: −31.40 min, 95% CI: −36.26 to −26.55 min), and greater SE (MD: 10.37%, 95% CI: 8.08% to 12.65%). The surface under the cumulative ranking curve indicates that web-based CBTi with therapists is most likely to be ranked the highest among all treatments, and thus, this network meta-analysis suggests that such a treatment is the optimal intervention for improving sleep duration and SE as well as the reductions in SOL and WASO. PROSPERO registration number CRD42020171134.

The aim of this systematic review was to investigate the effects of combined melatonin and bright light therapies on improved sleep and circadian outcomes. We conducted a systematic review that resulted in a total of eight papers meeting criteria. Four papers investigated the effectiveness of combined therapy in inducing a circadian phase shift on healthy participants. Combined therapy outperformed single light and melatonin therapies in phase advancing, but not in delaying, dim light melatonin onset (DLMO). The other four papers investigated the effect of combined therapy on sleep outcomes. Two of them were performed in elderly populations suffering from cognitive decline and two in delayed sleep-wake phase disorder (DSWPD) patients. While combined therapy was more beneficial than single therapy in elderly populations it did not show any benefit in DSWPD patients. The reported adverse effects of melatonin in elderly populations must be carefully considered. Future studies should investigate the separate and combined effect of melatonin and bright light on sleep and circadian outcomes in different target populations.

Cognitive behavioural therapy for insomnia (CBT-I) is a promising intervention with established efficacy, yet evidence of its cost-effectiveness remains unclear. Systematic searches were conducted in Medline, Psychinfo, ProQuest, Cochrane, Scopus, CINAHL, Web of Science and Emcare. Titles and abstracts were screened against eligibility criteria, and studies reporting full economic evaluations of CBT-I in adult populations were included and examined in detail. Study characteristics were extracted using a standardised template. Quantitative measures and relevant findings were summarised using a qualitative approach following recommended reporting standards. 1,168 non-duplicate articles were identified, of which 44 were selected for full-text review. Seven full economic evaluations of CBT-I in adult populations met the inclusion criteria and were incorporated in the final synthesis. Using the dominance ranking framework to compare cost and outcomes, CBT-I was cost-effective compared to pharmacotherapy or no treatment. The limited number of studies included in this review implies that caution should be exercised when interpreting these results. Future studies are encouraged to employ longer time-horizons and larger sample sizes to enable better determination of sustained cost and outcomes changes. Prospero registration number: CRD42019133554.

There is conflicting evidence on the clinical efficacy of exogenous melatonin for the treatment of sleep disorders. This may be due to differences in the pharmacokinetic (PK) properties of melatonin formulations used in clinical trials. The aim of this systematic review was to understand the relationship between melatonin formulations and PK parameters and, where possible, the effects on sleep outcomes. To this purpose, we conducted a systematic review and nineteen papers were included. The studies included three melatonin transdermal formulation, thirteen oral formulations, one topical, two buccal, two intravenous and two nasogastric formulations. Seven studies investigated the effect of the melatonin formulation on sleep and six of them found a significant improvement in one or more sleep parameters. The potential for an improved controlled release formulation that delays maximum concentration (Cmax) was identified. The different formulations and doses affect melatonin PK, suggesting that treatment efficacy maybe affected. Based on the current evidence, we are unable to provide recommendations of specific melatonin formulations and PK parameters for specific sleep disorders. Future studies should systematically investigate how different PK parameters of melatonin formulations affect efficacy treatment of sleep as well as circadian disorders.

Although cognitive behavioural therapy for insomnia (CBTi) is the recommended 'first-line' treatment for insomnia, most patients are initially treated with sedative-hypnotic medications. Given the risk of impaired cognitive and psychomotor performance, serious adverse events, and long-term dependence associated with sedative-hypnotics, guidelines recommend that prescriptions should be limited to short-term use and that patients are provided with support for withdrawal where possible. CBTi is an effective insomnia treatment in the presence of sedative-hypnotic use. Furthermore, guidelines recommended that CBTi techniques are utilised to facilitate withdrawal from sedative-hypnotics. However, there is very little research evaluating the effect of CBTi on reduced medication use. The current narrative review integrates 95 studies including over 10,000 participants, investigating the effect of CBTi on reduced sedative-hypnotic use in different populations (e.g., hypnotic-dependent patients, older adults, military personnel), settings (e.g., primary care settings, psychiatric inpatients), CBTi modalities (e.g., self-administered reading/audio materials, digital, and therapist-administered), and in combination with gradual dose reduction programs. Based on this research, we discuss the theoretical mechanistic effects of CBTi in facilitating reduced sedative-hypnotic use, provide clear recommendations for future research, and offer pragmatic clinical suggestions to increase access to CBTi to reduce dependence on sedative-hypnotics as the 'default' treatment for insomnia.

The aim of this meta-analysis was to compare the pooled sensitivity and specificity of the Pediatric Sleep Questionnaire (PSQ), Obstructive Sleep Apnea Questionnaire (OSA-18), and pulse oximetry (PO) according to OSAS severity. Three electronic databases were searched for studies evaluating sensitivity and specificity of the three tools against the apnea-hypopnea index measured using overnight in-laboratory or in-home polysomnography in children and adolescents from inception until January 11, 2020. A random-effects bivariate model was used to estimate the summary sensitivity and specificity of the tools. We identified 39 studies involving 6131 clinical and community children (aged 2.9-16.7 y). The PSQ exhibited the highest sensitivity (74%) for detecting symptoms of mild pediatric OSAS. The PSQ and PO had comparable sensitivity in screening moderate and severe pediatric OSAS (0.82 and 0.89 vs 0.83 and 0.83, respectively). PO yielded superior specificity in detecting mild, moderate, and severe pediatric OSAS (86%, 75%, and 83%, respectively) than did the PSQ and OSA-18 (all p 0.05). Age, percentage of girls, index test criteria, methodology quality, and sample size significantly moderated sensitivity and specificity. For early detection of pediatric OSAS, the combined use of PSQ and PO is recommended when polysomnography is not available. PROSPERO REGISTRATION NUMBER: CRD42018090571.

Heart rate variability (HRV) is an objective marker that provides insight into autonomic nervous system dynamics. There is conflicting evidence regarding the presence of HRV impairment in insomnia patients. Web-based databases were used to systematically search the literature for all studies that compared the HRV of insomnia patients to controls or reported the HRV of insomnia patients before and after an intervention. 22 relevant papers were identified. Study characteristics were summarised, HRV measures were extracted and a risk of bias assessment for each study was performed. We were limited in our ability to synthesise outcome measures and perform meta-analyses due to considerable differences in patient (and control) selection, study protocols, measurement and processing techniques and outcome reporting. Risk of bias was deemed to be high in the majority of studies. As such, we cannot confirm that HRV is reliably impaired in insomnia patients nor determine the HRV response to interventions. Whilst HRV impairment in insomnia is a widely accepted concept, it is not supported by empirical evidence. Large longitudinal studies incorporating 24-hour recordings are required to elucidate the precise nature of HRV dynamics in insomnia patients.