Effect of partial and total sleep deprivation on serum testosterone in healthy males: a systematic review and meta-analysis

BackgroundCurrently, there is no consensus on the effect of sleep deprivation on male serum testosterone. This systematic review and meta-analysis aimed to determine the association between partial/total sleep deprivation and male serum testosterone level.MethodsThe literature related to sleep deprivation and male serum testosterone in the PubMed, Embase, and Cochrane Library databases were searched from their inception to July 15, 2021. Data were pooled using the Stata 15 software. The results were presented as standard mean differences (SMDs) with their 95% confidence intervals (CIs).ResultsEighteen studies involving 252 men were included in the systematic review and meta-analysis. The findings revealed that short-term partial sleep deprivation had no significant effect on male serum testosterone (SMD = −0.22; 95% CI: −0.5, 0.06; P = 0.13), while total sleep deprivation reduced the male testosterone levels (SMD = −0.64; 95% CI: −0.87, −0.42; P < 0.001). According to the intervention duration of total sleep deprivation, subgroup analysis was conducted by a fixed-effects model. The results revealed that the serum testosterone was significantly decreased after 24 h total sleep deprivation (SMD = − 0.67; 95% CI = − 0.93, −0.42, P < 0.001), as well as 40–48 h total sleep deprivation (SMD = − 0.74; 95% CI = − 1.22, −0.26, P = 0.002).ConclusionsThis meta-analysis revealed that total sleep deprivation (more than or equal to 24 h) reduces the male testosterone levels, while short-term partial sleep deprivation has no significant effect on male serum testosterone. Sleep duration plays a pivotal role in maintaining male serum testosterone levels.     

The effects of prazosin on sleep disturbances in post-traumatic stress disorder: a systematic review and meta-analysis

BackgroundNightmares are a highly prevalent and distressing feature of post-traumatic stress disorder (PTSD). Previous studies have reached mixed conclusions regarding the effects of prazosin on nightmares, sleep quality, and overall PTSD symptoms in patients with PTSD.MethodsMEDLINE, EMBASE, all EBM databases, PsycIFNO, and CINAHL were systematically searched from inception date to October 2018 for randomized clinical trials that included reporting of nightmares, sleep quality or overall PTSD symptoms. The analysis included data from eight trials involving 286 PTSD patients in the prazosin group and 289 PTSD patients in the placebo group.ResultsIn our meta-analysis, prazosin resulted in a statistically significant improvement in nightmares (standardized mean difference (SMD) = −1.13, 95% confidence interval (CI) = −1.91 to −0.36), but was not more beneficial than placebo for overall PTSD symptoms (SMD = −0.45, 95% CI = −0.95 to 0.05) and sleep quality (SMD = −0.44, 95% CI = −1.44 to 0.55). In terms of acceptability, there was no significant difference between the prazosin group and the placebo group with respect to discontinuation for all causes (odds ratio (OR) = 1.00, 95% CI = 0.62–1.62). In conclusion, the use of prazosin was associated with an improvement of nightmare symptoms.ConclusionOur findings indicate that additional studies are needed before considering downgrading the use of prazosin in the treatment of nightmares in patients with PTSD.     

Abnormal night sleep duration and poor sleep quality are independently and combinedly associated with elevated depressive symptoms in Chinese rural adults: Henan Rural Cohort

ObjectiveTo assess the independent and combined effects of night sleep duration and sleep quality on depressive symptoms.MethodsA total of 28,202 participants (11,236 males and 16,966 females) aged 18–79 years from the Henan Rural Cohort were included in this study. Night sleep duration and sleep quality were defined by the Pittsburgh Sleep Quality Index (PSQI). Logistic regression and restricted cubic splines were applied to evaluate the association of night sleep duration and sleep quality with depressive symptoms.ResultsA U-shaped dose-response relationship between night sleep duration and depressive symptoms along with a J-shaped relationship between sleep quality and depressive symptoms were observed. Compared with reference group (7-<8 h), shorter sleep duration (<6 h) and longer sleep duration (≥10 h) were associated with increased risk of depressive symptoms in males (short sleep: Odds Ratio (OR) = 1.84, 95% confidence interval (CI), 1.34–2.52; long sleep: OR = 1.56, 95% CI, 1.01–2.42) and females (short sleep: OR = 2.19, 95% CI, 1.77–2.70; long sleep: OR = 1.51, 95% CI, 1.10–2.10). Compared with good sleepers, poor sleepers had 4.23-fold (95% CI:3.54–5.06) and 3.87-fold (95% CI: 3.41–4.40) increased odds of depressive symptoms in males and females. Furthermore, participants with longer night sleep duration (≥10 h) and poorer sleep quality had the strongest effect on depressive symptoms (males: OR = 6.64, 95% CI, 3.21–13.74; females: OR = 7.76, 95% CI, 5.00–12.02).ConclusionsExtreme night sleep duration and poor sleep quality were independently and combinedly related to elevated depressive symptoms, suggesting that keeping optimal night sleep duration and good sleep quality maybe benefit for maintaining mental health.Trial registrationChinese Clinical Trial Register. Registration number: ChiCTR-OOC-15006699.     

A meta-analysis of the relationship between subjective sleep and depressive symptoms in adolescence

BackgroundAdolescence is a risk period for the development of mental illness, as well as a time for pronounced change in sleep behaviour. While prior studies, including several meta-analyses show a relationship between sleep and depressive symptoms, there were many inconsistences found in the literature.ObjectiveTo investigate the relationship between subjective sleep and depressive symptoms.MethodsFollowing PRISMA guidelines, we conducted a literature search that yielded forty-nine recent studies (2014–2020) with adolescent samples aged 9 to 25-year-olds, and more than double the sample size of previous meta-analyses (N = 318,256).ResultsIn a series of meta-analyses, we show that while several common categories of subjective sleep are associated with depressive symptoms in adolescents, the strength of this relationship varies. Measures of sleep perception: poor sleep quality (r = 0.41), insomnia (r = 0.37), sleep disturbances (r = 0.36), wake after sleep onset (r = 0.31), and daytime sleepiness (r = 0.30) correlated more strongly with depressive symptoms, than measures of sleep behaviour: sleep latency (r = 0.22), and sleep duration (r = −0.19).ConclusionsThese findings suggest that in studies of depressive symptoms it may be important to assess an adolescent's perception about their sleep, in addition to their sleep/wake behaviours.     

Sleep in adults with Autism Spectrum Disorder: a systematic review and meta-analysis of subjective and objective studies

Background/ObjectiveSleep problems are commonly reported by individuals with Autism Spectrum Disorder (ASD). However, to date, no quantitative evidence synthesis of available studies has been performed to quantify sleep alterations in adults with ASD. We performed a systematic review and meta-analysis of objective (ie, based on actigraphy or polysomnography [PSG]) and subjective (ie, based on sleep diaries/questionnaires) studies comparing sleep parameters in adults with ASD and in a typically developing (TD) control group.MethodsPubMed, OVID databases and Web of Knowledge were systematically searched up to February 2019 with no language restrictions. Original studies including adults with a diagnosis of ASD according to DSM, ICD, or based on standard diagnostic tools (eg, ADOS), and a TD control group were included. Random-effects models were used. Study quality was evaluated with the Newcastle Ottawa Scale (NOS). Analyses were conducted using Comprehensive Meta-Analysis.ResultsFrom initial pool of 1948 references, 14 publications including 8 datasets, (194 ASD and 277 controls) met the inclusion criteria. Compared to controls, individuals with ASD were significantly more impaired in six out of 11 subjective parameters, including lower sleep efficiency (SE, SMD = −0.87, CI = −1.14 – 0.60) and in 10 out of 17 objective outcomes, including longer sleep onset latency (PSG) (SMD = 0.86, CI = 0.29–1.07) and wake after sleep onset (WASO, actigraphy) (SMD = 0.57, CI = 0.28–0.87). The mean NOS score was 4.88/6.ConclusionsIndividuals with ASD demonstrated impaired sleep compared to controls in most subjective and objective measures.     

The Role of Intraspinal Administration of Self-Assembled Peptide on Locomotion Recovery After Spinal Cord Injury: A Systematic Review and Meta-Analysis Study

BackgroundSpinal cord injury (SCI) treatment is still a challenge and new treatments that help these patients are being considered. Recent studies showed that the use of self-assembled peptide (SAP) can be useful in SCI treatment.Materials and MethodsIn this meta-analysis, we investigated the effect of SAP administration on locomotion recovery after SCI. Records were obtained from a comprehensive search of data bases. Articles were scrutinized for inclusion and exclusion criteria. Data were analyzed and results were reported as standardized mean difference (SMD) with 95% CI. Subgroup analysis was also performed.ResultsA total of 14 studies and 17 separate experiments were included in the final analysis. Treatment with SAP structures after SCI resulted in a significant improvement in animal motor function (SMD = 1.13; 95% CI: 0.68–1.58; p < 0.0001). SAP treatment facilitated axon sprouting (SMD = 0.76; 95% CI: 0.33–1.18; p < 0.0001) and reduction of glial scar (SMD = −1.02; 95% CI: −1.94 to −0.09; p = 0.03). The difference in SAP type, its concentration, follow-up time, and SCI model had no effect on SAP effectiveness. In addition, SAP administration had a similar effect on improving locomotion in all three immediate, acute, and subacute phases which gives the good news of using this treatment for patients who are in the chronic phase.ConclusionSAP treatment can be considered as a potential treatment to help the motor recovery of SCI and axon regeneration.     

Accumulation of affective symptoms and midlife cognitive function: The role of inflammation

BackgroundThe aim of the present study was to test whether C-Reactive Protein (CRP), a proxy measure of inflammation, is elevated in people with higher childhood and adulthood affective symptoms and whether elevated CRP predicts midlife cognitive function.MethodsData were used from the National Child Development Study (n = 6276). Measures of memory, verbal fluency, information processing speed and accuracy were available in midlife (age 50). Affective symptoms were assessed in childhood (ages 7, 11, 16) and in adulthood (ages 23, 33, 42, 50). The level of plasma CRP was measured at age 44. Pathway models, unadjusted and fully adjusted for sex, education, childhood socioeconomic position, childhood cognitive ability and affective symptoms at age 50, were fitted to test direct associations between affective symptoms and midlife cognitive function, and indirect associations via the inflammatory pathway (CRP level).ResultsIn a fully adjusted model, there were significant indirect associations between adulthood affective symptoms and immediate memory (β = −0.01, SE = 0.003, p = .03) and delayed memory (β = −0.01, SE = 0.004, p = .03) via CRP. In addition, there were significant indirect associations between affective symptoms in childhood and immediate memory (β = −0.001, SE = 0.00, p = .03) and delayed memory (β = −0.001, SE = 0.001, p = .03), via adulthood affective symptoms and associated CRP. Independent of CRP, there was a significant direct association between adulthood affective symptoms and information processing errors (β = 0.47, SE = 0.21, p = .02). There were no direct or indirect associations between affective symptoms and verbal fluency or information processing speed.ConclusionsCRP at age 44 is elevated in people with higher affective symptoms from age 7 to 42, and elevated CRP is associated with poorer immediate and delayed memory at age 50.     

Assessing the causal associations of insomnia with depressive symptoms and subjective well-being: a bidirectional Mendelian randomization study

BackgroundThe interactions and associations between insomnia, depressive symptoms, and subjective well-being are complex, thus it is hard to explore the effect and direction of causalities. This bidirectional Mendelian randomization (MR) study was to assess the causal associations of insomnia with depressive symptoms and subjective well-being.MethodsSummary statistics for insomnia, depressive symptoms, and subjective well-being were obtained from three large-scale genome-wide association studies (GWAS) of European ancestry. MR analyses were mainly conducted with the inverse-variance-weighted (IVW) method. The weighted-median method, MR-Egger method, and MR-Pleiotropy RESidual Sum and Outlier (PRESSO) test were adopted to test whether the estimates were robust. The adjusted MR analysis was performed to avoid the effect of potential pleiotropy.ResultsThere was evidence to support a causal association between genetically predicted insomnia and depressive symptoms (beta (β) = 0.086, 95% confidence interval (CI) = 0.068 to 0.104, P = 8.6E-21). Meanwhile, genetically predicted depressive symptoms was associated with a higher risk of insomnia (β = 0.543, 95% CI = 0.331 to 0.754, P = 4.8E-07). Genetically predicted insomnia was negatively associated with subjective well-being (β = −0.043, 95% CI = −0.063 to −0.024, P = 1.2E-05). There was evidence of reverse causality between insomnia and subjective well-being (β = −0.821, 95% CI = −1.012 to −0.630, P = 4.0E-17).ConclusionsMR analysis indicates bidirectional causal associations of insomnia with depressive symptoms and subjective well-being. People should give serious attention to and attempt to resolve the problems of insomnia, depressive symptoms, and subjective well-being, whichever comes first.     

The effect of repetitive transcranial magnetic stimulation for insomnia: a systematic review and meta-analysis

BackgroundRepetitive transcranial magnetic stimulation (rTMS) might be a promising technique in treating insomnia. A comprehensive meta-analysis of the available literature is conducted to offer evidence.ObjectiveTo evaluate the efficacy and safety of rTMS for insomnia, either as monotherapy or as a complementary strategy.MethodsCENTRAL, PubMed, EMBASE, PsycINFO, CINAHL, PEDro, CBM, CNKI, WANFANG, and VIP were searched from earliest record to August 2019. Randomized control trials (RCTs) published in English and Chinese examining effects of rTMS on patients with insomnia were included. Two authors independently completed the article selection, data extraction and rating. Physiotherapy Evidence Database (PEDro) scale was used to assess the methodological quality of the included studies. The RevMan software was used for meta-analysis. The quality of the evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsA total of 36 trials from 28 eligible studies were included, involving a total of 2357 adult participants (mean age, 48.80 years; 45.33% males). Compared with sham rTMS, rTMS was associated with improved PSQI total score (SMD −2.31, 95% CI −2.95 to −1.66; Z = 7.01, P < 0.00001) and scores of seven subscales. Compared to other treatment, rTMS as an adjunct to other treatment was associated with improved PSQI total score (SMD −1.44, 95% CI −2.00 to −0.88; Z = 5.01, P < 0.00001), and may have effects on scores of seven subscales. Compared with other treatment, rTMS was associated with improved Pittsburgh sleep quality index (PSQI) total score (SMD −0.63, 95% CI −1.22 to −0.04; Z = 2.08, P = 0.04), and may have a better score in sleep latency, sleep disturbance and hypnotic using of seven subscales. In the three pair of comparisons, the results for polysomnography (PSG) outcomes were varied. In general, rTMS may improve sleep quality through increasing slow wave and rapid eye movement (REM) sleep. The rTMS group was more prone to headache than the sham or blank control group (RR 1.71, 95% CI 1.03 to 2.85; Z = 2.07, P = 0.04). No severe adverse events were reported. Reporting biases and low and very low grade of some evidences should be considered when interpreting the results of this meta-analysis.ConclusionsOur findings indicate that rTMS may be a safe and effective option for insomnia. Further international, multicenter, high-quality RCTs with more objective, quality of life related and follow-up assessments are needed.     

Association between night-shift work and level of melatonin: systematic review and meta-analysis

BackgroundsNight-shift workers are exposed to nocturnal light and are more prone to circadian rhythm disorders. Although night-shift work is thought to be associated with the decrease in melatonin secretion, studies have shown inconsistent results.MethodsThis systematic review and meta-analysis studied the association between night-shift work and melatonin levels. Pubmed and Embase databases were used for literature searching. The pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to compare the differences between night-shift workers and the controls.ResultsThirty-three studies reported in 25 articles (1845 night-shift workers and 3414 controls, mean age 45.12 years) were included after a systematic literature review. Data of circulating melatonin levels and its metabolites, 6-sulfatoxymelatonin (aMT6s) in urine were collected for meta-analysis. The results showed that the first morning-void aMT6s level in night-shift workers was significantly lower than in day workers (SMD = −0.101, 95% CI = −0.179 to −0.022, P = 0.012). The level of mean 24-h urinary aMT6s was lower in night-shift workers than day workers (SMD: −0.264, 95% CI: −0.473 to −0.056, P = 0.013). Among fixed night-shift workers, the level of circulating melatonin, as well as first morning-void aMT6s was lower than that of day workers.ConclusionOur findings indicate that experience of night-shift work is associated with suppression of melatonin production, especially among fixed night-shift workers.     

MRI-visible perivascular space volumes,sleep duration and daytime dysfunction in adults with cerebrovascular disease

ObjectivesRecent studies suggest that interindividual genetic differences in glial-dependent CSF flow through the brain parenchyma, known as glymphatic flow, may trigger compensatory changes in human sleep physiology. In animal models, brain perivascular spaces are a critical conduit for glymphatic flow. We tested the hypothesis that MRI-visible PVS volumes, a putative marker of perivascular dysfunction, are associated with compensatory differences in real-world human sleep behavior.MethodsWe analyzed data from 152 cerebrovascular disease patients from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). PVS volumes were measured using 3T-MRI. Self-reported total sleep time, time in bed, and daytime dysfunction were extracted from the Pittsburgh Sleep Quality Index.ResultsIndividuals with greater PVS volumes reported longer time in bed (+0.85 h per log10 proportion of intracranial volume (ICV) occupied by PVS, SE = 0.30, p = 0.006) and longer total sleep times (+0.70 h per log10 proportion of ICV occupied by PVS volume, SE = 0.33, p = 0.04), independent of vascular risk factors, sleep apnea, nocturnal sleep disturbance, depression, and global cognitive status. Further analyses suggested that the positive association between PVS volumes and total sleep time was mediated by greater time in bed. Moreover, despite having on average greater total sleep times, individuals with greater basal ganglia PVS volumes were more likely to report daytime dysfunction (OR 5.63 per log10 proportion of ICV occupied by PVS, 95% CI: 1.38–22.26, p = 0.018).ConclusionsIndividuals with greater PVS volumes spend more time in bed, resulting in greater total sleep time, which may represent a behavioral compensatory response to perivascular space dysfunction.     

Efficacy of intradermal acupuncture for insomnia: a meta-analysis

ObjectivesTo provide updated evidence from randomized controlled trials (RCTs) on the efficacy of intradermal acupuncture for insomnia.MethodsA search of relevant literatures was performed on major medical databases, including the Cochrane Library, PubMed, EMBASE, CBM, CNKI, VIP, Wanfang Data and so on. Risk of bias evaluation, meta-analysis, sensitivity analysis and evidence rating of all extracted information were also conducted.ResultsA total of 508 studies were initially identified. However, only 45 studies were deemed eligible for the present review. Meta-analyses were conducted in three comparisons separately: intradermal versus acupuncture, Effective rate (RR = 0.08, 95% CI -0.02 to 0.19), Global scales score (points) (SMD = −0.52, 95% CI: −0.81,−0.24, P = 0.02); intradermal acupuncture versus non acupuncture, Effective rate(RR = 1.22, 95% CI 1.04 to 1.42), Global scales score (points) (SMD = −0.81, 95% CI: −1.23,−0.38, P < 0.00001); control group versus control add intradermal acupuncture. Effective rate(RR = 1.27, 95% CI 1.13 to 1.42), Global scales score (points) (SMD = −1.15, 95% CI: −1.46,−0.84, P < 0.00001). Although these results suggested benefits of intradermal acupuncture, the overall quality of evidence rated was low.ConclusionsThe summary estimates indicate that it improved the clinical effective rate and lowered PSQI or other scales score, when compared to sham acupuncture or placebo/conventional medications/herbs.Also,it significantly improved the clinical effective rate and lowered PSQI or other scales score, when the control groups add intradermal acupuncture. However, the quality of the evidence is varied from very low to low due to the potential risk of bias and inconsistency among included trials. The more larger sample size and much more rigorous designed RCTs are still further studied.     

The efficacy of integrated cognitive behavioral therapy (CBT) and acupressure versus CBT for insomnia: a three-arm pilot randomized controlled trial

ObjectivesThis pilot study aimed to examine the efficacy of integrated cognitive behavioral therapy (CBT) and acupressure in treating insomnia and its daytime impairments in a Chinese adult population.Methods40 eligible participants with insomnia were randomly assigned to either the integrated CBT and acupressure (CBTAcup) group (n = 14), the CBT group (n = 13), or the waitlist control (WL) group (n = 13). Participants in the CBTAcup group attended a 2-hour integrated CBT and self-administered acupressure group treatment once per week for six consecutive weeks, while participants in the CBT group attended six weekly 2-hour CBT for insomnia. Sleep, mood, daytime impairments, quality of life, and treatment credibility and adherence were assessed at baseline, immediate post-treatment (Week 7), and 4-week post-treatment (Week 11).ResultsLinear mixed-effects models showed that both the CBTAcup and CBT groups had significantly lower insomnia severity (d = −1.74 and d = −2.61), dysfunctional beliefs related to sleep (d = −2.17 and −2.76), and mental fatigue (d = −1.43 and −1.60) compared with the WL group at Week 7. The CBTAcup group provided additional benefits in reducing total fatigue (d = −1.43) and physical fatigue (d = −1.45). Treatment credibility was found to be improved in the CBTAcup group from baseline to Week 7.ConclusionsIntegrated CBT and acupressure demonstrated comparable efficacy to pure CBT in treating insomnia symptoms, with additional advantages to improve fatigue symptoms and acceptability in the Chinese population. Further methodologically rigorous studies on a larger scale and longer follow-up are warranted to confirm these findings.     

Efficacy of melatonin for sleep disturbance in middle-aged primary insomnia: a double-blind,randomised clinical trial

BackgroundThe aim of this study was to determine the efficacy of exogenous melatonin supplementation for sleep disturbances in patients with middle-aged primary insomnia.MethodsThis is a randomized double-blind, placebo-controlled parallel study. Participants were recruited from Tianlin community, Xuhui district, Shanghai. Ninety-seven consecutive middle-aged patients with primary insomnia were randomized to receive 3 mg fast-release melatonin (n = 51) or placebo (n = 46) for four-weeks. Objective sleep parameters tested by overnight polysomnography, subjective sleep performance and daytime somnolence obtained from the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS) were obtained at baseline and after treatment. Treatment was taken daily 1 h before bedtime. Serious adverse events and side-effects were monitored.ResultsMelatonin supplementation significantly decreased early wake time [−30.63min (95% CI, −53.92 to −7.34); P = 0.001] and percentage of N2 sleep [−7.07% (95% CI, −13.47% to −0.68%); P = 0.031]. However, melatonin had no significant effect on other objective sleep parameters including sleep latency, sleep efficiency, wake during the sleep and percent of N1, N3 and REM sleep. Melatonin had no effect on insomnia symptoms and severity on the PSQI [1.53(95% CI, −0.55 to 3.61); p = 0.504]; ISI [0.81 (95% CI, −2.27 to 3.88); p = 0.165] and ESS [−0.83 (95% CI, −3.53 to 1.88); p = 0.147]. No serious adverse events were reported.ConclusionsMelatonin supplementation over a four-week period is effective and safe in improving some aspects of objective sleep quality such as total sleep time, percentage of rapid eye movement and early morning wake time in middle-aged patients with insomnia.Trial registrationIdentifier: ChiCTR-TRC-13003997; Prospectively registered on 2 December 2013.     

Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials

ObjectiveTo evaluate the efficacy and safety of melatonin in the treatment of sleep onset insomnia in children and adolescents.MethodsElectronic databases and bibliographies of relevant reports were searched for randomized, placebo-controlled, clinical trials that used melatonin in children and adolescents with sleep onset insomnia. The quality of the included studies was assessed by the Cochrane Collaboration's risk-of-bias method. The mean differences (MD) and the odds ratios (OR) with 95% confidence interval (CI) were estimated by a random-effects model. Primary outcomes were sleep onset time (SOT), drop-out for all causes and drop-out for adverse events. Secondary outcomes included dim light melatonin onset (DLMO), sleep onset latency (SOL), total sleep time (TST), light-off time, and wake-up time.ResultsSeven trials with 387 participants were finally included after a systematic search. The overall quality of the included studies was low to moderate. SOT in patients receiving melatonin advanced more than patients receiving placebo (MD = −0.62 h, 95% CI −0.80, −0.45), as well as DLMO (MD = −0.82 h, 95% CI −1.23, −0.41). No differences were found in the outcome of drop-out for all causes (OR = 1.51, 95% CI 0.57, 4.05) or drop-out for adverse events (OR = 3.35, 95% CI 0.13, 86.03). Severe adverse events, migraine, and mild generalized epilepsy were reported in two cases. SOL decreased and TST increased, MD = −0.36 h (95% CI −0.49, −0.24) and MD = 0.38 h (95% CI 0.09, 0.66), respectively. Light-off time and wake-up time did not differ significantly.ConclusionsMelatonin was an effective and tolerable drug in the short-term treatment of sleep onset insomnia in children and adolescents. More studies, especially in adolescents, are needed to investigate the efficacy and safety of melatonin.     

Sleep and circadian rhythm alterations correlate with depression and cognitive impairment in Huntington's disease

ObjectiveSleep disturbances are a prominent feature of Huntington's disease (HD) and can substantially impair patients' quality of life. However, sleep complaints and their association with other symptoms and signs of HD have not yet been assessed in large groups of patients or premanifest mutation carriers. Therefore, we aimed to delineate the nature of subjective sleep disturbances and identify important correlates of sleep impairment in HD patients and premanifest mutation carriers.Subjects & methodsUsing standardized questionnaires (including Epworth's Sleepiness Scale, Pittsburgh Sleep Quality Index, SCOPA-SLEEP, and Beck's Depression Inventory), daytime sleepiness, night-time sleep, and depressed mood were assessed in 63 HD patients, 21 premanifest mutation carriers and 84 controls.ResultsNight-time sleep impairment was significantly more prevalent in HD patients compared with controls (58.1% vs. 34.9%, p = 0.012), but daytime sleepiness was not (12.7% vs. 7.9%, p = 0.560). Depression was the only independent correlate of night-time sleep impairment in HD patients, accounting for 10% of the variance. Compared with controls, both sleep onset latency and wake-up time were significantly delayed in HD patients. Moreover, in HD patients, later wake-up time was significantly associated with cognitive score (r = −0.43), total functional capacity (r = −0.54) and depressive symptoms (r = +0.47). In general, the degree of sleep (phase) changes in premanifest mutation carriers lay in between those of HD patients and controls.ConclusionsHD is primarily accompanied by night-time sleep disturbances and a delayed sleep phase, which are associated with depression and lower cognitive as well as functional performance.     

Management of Cancer-Related Pain With Intrathecal Drug Delivery: A Systematic Review and Meta-Analysis of Clinical Studies

BackgroundDespite increased attention paid to assessment and management, pain continues to be a prevalent and undertreated symptom in patients with cancer. Intrathecal drug delivery (IDD) is a therapeutic option that allows targeted delivery of analgesics to the intrathecal space.ObjectiveThe aim of this review was to examine the efficacy of managing cancer-related pain with IDD. Secondary objectives included the effects of IDD on systemic opioid use and infection rates.Evidence ReviewA systematic search of the literature published between 1990 and 2019 was performed to identify studies evaluating the efficacy and/or safety of IDD with external or implanted pumps in patients with cancer-related pain. Data were extracted and meta-analyses performed to determine the mean changes in pain levels at short-, mid-, and long-term intervals; changes in opioid (oral morphine equivalent [OME]) daily dose; and infection rates. Changes were assessed compared with baseline.FindingsPain levels were decreased from baseline: On a 0 to 10 scale, mean differences were −4.34 (95% CI [−4.93 to −3.75], p < 0.001) at 4 to 5 weeks; −4.34 (95% CI [−5.07 to −3.62], p < 0.001) at 6 to 12 weeks; and −3.32 (95% CI [−4.60 to −2.04], p < 0.001) at >6 months. Weighted mean OME consumption was reduced by 308.24 (SE = 22.72) mg/d. Weighted mean infection rates were ∼3% for external and implanted pumps.ConclusionsMeta-analyses show a statistically significant and sustained decrease in cancer pain with IDD, compared with baseline. Systemic opioid consumption was reduced on average by >50% after IDD. Infection rates were comparable with other indications.     

A quantitative analysis of the effect of bilateral subthalamic nucleus-deep brain stimulation on subjective and objective sleep parameters in Parkinson's disease

ObjectiveTo explore how subjective and objective sleep parameters respond to bilateral subthalamic nucleus-deep brain stimulation (STN-DBS) in patients with Parkinson's disease (PD).MethodsThirty DBS sleep studies were included by searching PubMed, Embase, and the Cochrane Library, and only 21 prospectively designed studies, including 541 patients, were eligible for the main analysis. We evaluated sleep disturbance using 1 objective measurement, polysomnography (PSG), and 4 subjective scales, including PD Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and restless legs syndrome (RLS). We pooled data using the standard mean difference (SMD). The primary outcome was a change in sleep parameters 6 months postoperatively. Outcomes from <12 months to ≥12 months follow-up were compared in the subgroup analysis. Meta-regression was further conducted.ResultsSTN-DBS significantly improved all 4 subjective sleep scales in the 6-month follow-up: ESS (SMD = 0.234), PDSS (SMD = 0.724), PSQI (SMD = 1.374) and RLS (SMD = 1.086), while most PSG parameters remained unchanged, except for shortened rapid eye movement sleep latency (RSL) (SMD = 0.520). In the over-12-month follow-up, improvement persisted in PDSS but not in ESS. Dopamine drug reduction (p = 0.009) and motor improvement (p = 0.036) were correlated with ESS improvement and PDSS improvement, respectively.ConclusionsBilateral STN-DBS continuously improved subjective nocturnal sleep, while its effect on ESS lasted for only 1 year. Medication reduction and motor improvement may contribute to improved daytime sleepiness and better subjective nocturnal sleep, respectively. Except for a shortened RSL, STN-DBS did not change PSG parameters, including sleep efficiency and sleep architecture.RegistrationOpen Science Framework: DOI 10.17605/OSF.IO/3EGRC.