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1.
Approved cannabinoids for medical purposes - Comparative systematic review and meta-analysis for sleep and appetite.
Spanagel, R, Bilbao, A
Neuropharmacology. 2021;:108680
Abstract
BACKGROUND Cannabinoids are used for numerous disease indications. However, cannabinoids can also produce adverse effects; for example, they can disturb physiological functions such as sleep and appetite. The medical use of cannabinoids refers to a wide variety of preparations and products. Approved cannabinoid products include dronabinol ((-)-trans-Δ9-tetrahydrocannabinol (THC), nabilone (a THC analogue), and cannabidiol (CBD) that differ in their pharmacology and may thus have different adverse effects on sleep and appetite. OBJECTIVES Here we ask if (i) cannabinoids decrease sleep and appetite in somatic patients or patients that suffer from mental illness and if (ii) there is a difference between THC products (nabilone, dronabinol), vs. CBD in disturbing these physiological functions. METHODS In order to answer these two questions, we performed a comparative systematic review (SR) for nabilone, dronabinol, and CBD. For the comparative SR we searched PubMed, Medline, Embase, and PsycINFO for randomized controlled trials (RCTs) and extracted information for adverse side effects or outcomes reporting a negative impact on sleep and appetite. RCT evidence was calculated as odds ratios (ORs) via fixed effects meta-analyses. Evidence quality was assessed by the Cochrane Risk of Bias and GRADE tools. This study is registered at PROSPERO (CRD42021229932). FINDINGS A total of 17 RCTs (n = 1479) and 15 RCTs (n = 1974) were included for sleep and appetite, respectively. Pharmaceutical THC (nabilone, dronabinol) does not affect sleep or appetite. In contrast, there is moderate evidence that CBD decreases appetite (OR = 2.46 [1.74:4.01] but has also no effect on sleep. INTERPRETATIONS Our comparative systematic study shows that approved cannabinoids can decrease appetite as a negative side effect - an effect that seems to be driven by CBD. Approved cannabinoid products do not negatively affect sleep in somatic and psychiatric patients. This article is part of the special Issue on "Cannabinoids".
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2.
The effects of saffron (Crocus sativus L.) on mental health parameters and C-reactive protein: A meta-analysis of randomized clinical trials.
Ghaderi, A, Asbaghi, O, Reiner, Ž, Kolahdooz, F, Amirani, E, Mirzaei, H, Banafshe, HR, Maleki Dana, P, Asemi, Z
Complementary therapies in medicine. 2020;:102250
Abstract
BACKGROUND The findings of trials investigating the effects of saffron (Crocus sativus L.) supplementation on depression, anxiety, and C-reactive protein (CRP) are inconsistent. The current meta-analysis of randomized controlled trials (RCTs) was carried out to assess the effects of saffron (Crocus sativus L.) administration on mental health parameters and CRP levels. METHODS Two independent authors systematically searched online databases including EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science from inception until 30th July 2019. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. The heterogeneity among the included studies was assessed using Cochrane's Q test and I-square (I2) statistic. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size. RESULTS Twenty one trials were included in this meta-analysis. Consumption of saffron resulted in a significant reduction in Beck Depression Inventory (BDI) (11 studies with 12 effect size) (WMD: -4.86; 95 % CI: -6.58, -3.14), Beck Anxiety Inventory (BAI) (5 studies) (WMD: -5.29; 95 % CI: -8.27, -2.31) and Pittsburgh Sleep Quality Index (PSQI) scores (3 studies with 4 effect size) (WMD: -2.22; 95 % CI: -2.73, -1.72). Saffron intake did not affect Hamilton Depression Rating Scale (HDRS-D), Hamilton Anxiety Rating Scale (HARS-A) scores and C-reactive protein (CRP) levels. CONCLUSIONS This meta-analysis demonstrated that saffron intake significantly reduced BDI, BAI and PSQI scores, but did not affect HDRS-D, HARS-A scores and CRP levels.
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3.
Sleep duration and cardiovascular risk factors in children and adolescents: A systematic review.
Sun, J, Wang, M, Yang, L, Zhao, M, Bovet, P, Xi, B
Sleep medicine reviews. 2020;:101338
Abstract
An association between short sleep duration and cardiovascular risk factors and outcomes is well demonstrated in adults. However, findings on the association in children and adolescents have been inconsistent. In this review, we searched PubMed, Embase and ISI Web of Science for eligible publications until March 16, 2020. We identified 37 reviews/meta-analyses on the association between sleep duration and cardiovascular risk factors and 15 studies on the association between sleep duration and metabolic syndrome (MetS) in children and adolescents. We found strong evidence on the association between short sleep duration and increased adiposity markers and high blood pressure, some evidence on the association between short sleep duration and insulin resistance, but inconsistent findings on the association between sleep duration and blood lipids, inflammation and MetS. Although more studies are needed to further assess the association between sleep duration and selected cardiovascular risk factors, our findings support interventions to improve sleep duration and quality as a potential means to promote cardiovascular health in children and adolescents.
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4.
Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep.
Cade, BE, Chen, H, Stilp, AM, Louie, T, Ancoli-Israel, S, Arens, R, Barfield, R, Below, JE, Cai, J, Conomos, MP, et al
PLoS genetics. 2019;(4):e1007739
Abstract
Sleep disordered breathing (SDB)-related overnight hypoxemia is associated with cardiometabolic disease and other comorbidities. Understanding the genetic bases for variations in nocturnal hypoxemia may help understand mechanisms influencing oxygenation and SDB-related mortality. We conducted genome-wide association tests across 10 cohorts and 4 populations to identify genetic variants associated with three correlated measures of overnight oxyhemoglobin saturation: average and minimum oxyhemoglobin saturation during sleep and the percent of sleep with oxyhemoglobin saturation under 90%. The discovery sample consisted of 8,326 individuals. Variants with p < 1 × 10(-6) were analyzed in a replication group of 14,410 individuals. We identified 3 significantly associated regions, including 2 regions in multi-ethnic analyses (2q12, 10q22). SNPs in the 2q12 region associated with minimum SpO2 (rs78136548 p = 2.70 × 10(-10)). SNPs at 10q22 were associated with all three traits including average SpO2 (rs72805692 p = 4.58 × 10(-8)). SNPs in both regions were associated in over 20,000 individuals and are supported by prior associations or functional evidence. Four additional significant regions were detected in secondary sex-stratified and combined discovery and replication analyses, including a region overlapping Reelin, a known marker of respiratory complex neurons.These are the first genome-wide significant findings reported for oxyhemoglobin saturation during sleep, a phenotype of high clinical interest. Our replicated associations with HK1 and IL18R1 suggest that variants in inflammatory pathways, such as the biologically-plausible NLRP3 inflammasome, may contribute to nocturnal hypoxemia.
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5.
Therapeutic efficacy and safety of chamomile for state anxiety, generalized anxiety disorder, insomnia, and sleep quality: A systematic review and meta-analysis of randomized trials and quasi-randomized trials.
Hieu, TH, Dibas, M, Surya Dila, KA, Sherif, NA, Hashmi, MU, Mahmoud, M, Trang, NTT, Abdullah, L, Nghia, TLB, Y, MN, et al
Phytotherapy research : PTR. 2019;(6):1604-1615
Abstract
This systematic review and meta-analysis aimed to study the efficacy and safety of chamomile for the treatment of state anxiety, generalized anxiety disorders (GADs), sleep quality, and insomnia in human. Eleven databases including PubMed, Science Direct, Cochrane Central, and Scopus were searched to retrieve relevant randomized control trials (RCTs), and 12 RCTs were included. Random effect meta-analysis was performed by meta package of R statistical software version 3.4.3 and RevMan version 5.3. Our meta-analysis of three RCTs did not show any difference in case of anxiety (standardized mean difference = -0.15, 95% CI [-0.46, 0.16], P = 0.4214). Moreover, there is only one RCT that evaluated the effect of chamomile on insomnia and it found no significant change in insomnia severity index (P > 0.05). By using HAM-A scale, there was a significant improvement in GAD after 2 and 4 weeks of treatment (mean difference = -1.43, 95% CI [-2.47, -0.39], P = 0.007), (MD = -1.79, 95% CI [-3.14, -0.43], P = 0.0097), respectively. Noteworthy, our meta-analysis showed a significant improvement in sleep quality after chamomile administration (standardized mean difference = -0.73, 95% CI [-1.23, -0.23], P < 0.005). Mild adverse events were only reported by three RCTs. Chamomile appears to be efficacious and safe for sleep quality and GAD. Little evidence is there to show its effect on anxiety and insomnia. Larger RCTs are needed to ascertain these findings.
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Genome-wide association meta-analysis and Mendelian randomization analysis confirm the influence of ALDH2 on sleep durationin the Japanese population.
Nishiyama, T, Nakatochi, M, Goto, A, Iwasaki, M, Hachiya, T, Sutoh, Y, Shimizu, A, Wang, C, Tanaka, H, Watanabe, M, et al
Sleep. 2019;(6)
Abstract
Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.
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7.
Daytime napping and risk of type 2 diabetes: a meta-analysis of prospective studies.
Chen, GC, Liu, MM, Chen, LH, Xu, JY, Hidayat, K, Li, FR, Qin, LQ
Sleep & breathing = Schlaf & Atmung. 2018;(3):815-824
Abstract
PURPOSE Prospective studies reported inconsistent findings on the relationship between daytime napping and risk of type 2 diabetes (T2D). Categorized and dose-response meta-analyses were performed to quantify this relation. METHODS Potentially eligible studies were identified by searching PubMed and Embase databases. Dose-response effects were assessed by the generalized least squares trend estimation and study-specific summary relative risks (RRs) with 95% confidence intervals (CIs) were computed with a random-effects model. RESULTS Seven prospective studies including one US, four European, and two Chinese cohorts involving 249,077 participants and 13,237 cases of T2D were included. The overall analyses showed a 17% increased risk of T2D when comparing habitual nappers with non-nappers (RR = 1.17, 95% CI 1.08-1.27). By region, the summary RR was 1.21 (95% CI 1.17-1.26), 1.15 (95% CI 1.03-1.30) and 1.23 (95% CI 0.87-1.73) for the US, European, and Chinese studies, respectively. Limiting to five studies that excluded subjects with known major chronic disorders yielded a summary RR of 1.16 (95% CI 1.03-1.30). A dose-response analysis suggested an 11% (95% CI 7-16%) increased T2D risk for each increment in daytime napping of 30 min/day and, despite no evidence for nonlinearity (P nonlinearity = 0.65), the increased risk of T2D for short nap (<50 min/day) was dominated by the US study. CONCLUSIONS This meta-analysis suggests that daytime napping is associated with an increased risk of T2D. Given the limited number of cohorts and inconsistency in terms of methodological and population characteristics across these cohorts, residual confounders and/or reverse causality cannot be fully addressed, and our findings should be interpreted with great caution. Future well-designed prospective studies are still warranted.
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Establishing normal values for pediatric nighttime sleep measured by actigraphy: a systematic review and meta-analysis.
Galland, BC, Short, MA, Terrill, P, Rigney, G, Haszard, JJ, Coussens, S, Foster-Owens, M, Biggs, SN
Sleep. 2018;(4)
Abstract
BACKGROUND Despite the widespread use of actigraphy in pediatric sleep studies, there are currently no age-related normative data. OBJECTIVES To systematically review the literature, calculate pooled mean estimates of actigraphy-derived pediatric nighttime sleep variables and to examine the magnitude of change with age. METHODS A systematic search was performed across eight databases of studies that included at least one actigraphy sleep variable from healthy children aged 0-18 years. Data suitable for meta-analysis were confined to ages 3-18 years with seven actigraphy variables analyzed using random effects meta-analysis and meta-regression performed using age as a covariate. RESULTS In total, 1334 articles did not meet inclusion criteria; 87 had data suitable for review and 79 were suitable for meta-analysis. Pooled mean estimates for overnight sleep duration declined from 9.68 hours (3-5 years age band) to 8.98, 8.85, 8.05, and 7.4 for age bands 6-8, 9-11, 12-14, and 15-18 years, respectively. For continuous data, the best-fit (R2 = 0.74) equation for hours over the 0-18 years age range was 9.02 - 1.04 × [(age/10)^2 - 0.83]. There was a significant curvilinear association between both sleep onset and offset with age (p < .001). Sleep latency was stable at 19.4 min per night. There were significant differences among the older age groups between weekday and weekend/nonschool days (18 studies). Total sleep time in 15-18 years old was 56 min longer, and sleep onset and offset almost 1 and 2 hours later, respectively, on weekend or nonschool days. CONCLUSION These normative values have potential application to assist the interpretation of actigraphy measures from nighttime recordings across the pediatric age range, and aid future research.
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9.
Signs and Symptoms of Primary Tooth Eruption: A Meta-analysis.
Massignan, C, Cardoso, M, Porporatti, AL, Aydinoz, S, Canto, Gde L, Mezzomo, LA, Bolan, M
Pediatrics. 2016;(3):e20153501
Abstract
CONTEXT Symptoms associated with the primary tooth eruption have been extensively studied but it is still controversial. OBJECTIVE To assess the occurrence of local and systemic signs and symptoms during primary tooth eruption. DATA SOURCES Latin American and Caribbean Health Sciences, PubMed, ProQuest, Scopus, and Web of Science were searched. A partial gray literature search was taken by using Google Scholar and the reference lists of the included studies were scanned. STUDY SELECTION Observational studies assessing the association of eruption of primary teeth with local and systemic signs and symptoms in children aged 0 to 36 months were included. DATA EXTRACTION Two authors independently collected the information from the selected articles. Information was crosschecked and confirmed for its accuracy. RESULTS A total of 1179 articles were identified, and after a 2-phase selection, 16 studies were included. Overall prevalence of signs and symptoms occurring during primary tooth eruption in children between 0 and 36 months was 70.5% (total sample = 3506). Gingival irritation (86.81%), irritability (68.19%), and drooling (55.72%) were the most frequent ones. LIMITATIONS Different general symptoms were considered among studies. Some studies presented lack of confounding factors, no clear definition of the diagnostics methods, use of subjective measures and long intervals between examinations. CONCLUSIONS There is evidence of the occurrence of signs and symptoms during primary tooth eruption. For body temperature analyses, eruption could lead to a rise in temperature, but it was not characterized as fever.
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10.
Common variants in DRD2 are associated with sleep duration: the CARe consortium.
Cade, BE, Gottlieb, DJ, Lauderdale, DS, Bennett, DA, Buchman, AS, Buxbaum, SG, De Jager, PL, Evans, DS, Fülöp, T, Gharib, SA, et al
Human molecular genetics. 2016;(1):167-79
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Abstract
Sleep duration is implicated in the etiologies of chronic diseases and premature mortality. However, the genetic basis for sleep duration is poorly defined. We sought to identify novel genetic components influencing sleep duration in a multi-ethnic sample. Meta-analyses were conducted of genetic associations with self-reported, habitual sleep duration from seven Candidate Gene Association Resource (CARe) cohorts of over 25 000 individuals of African, Asian, European and Hispanic American ancestry. All individuals were genotyped for ∼50 000 SNPs from 2000 candidate heart, lung, blood and sleep genes. African-Americans had additional genome-wide genotypes. Four cohorts provided replication. A SNP (rs17601612) in the dopamine D2 receptor gene (DRD2) was significantly associated with sleep duration (P = 9.8 × 10(-7)). Conditional analysis identified a second DRD2 signal with opposite effects on sleep duration. In exploratory analysis, suggestive association was observed for rs17601612 with polysomnographically determined sleep latency (P = 0.002). The lead DRD2 signal was recently identified in a schizophrenia GWAS, and a genetic risk score of 11 additional schizophrenia GWAS loci genotyped on the IBC array was also associated with longer sleep duration (P = 0.03). These findings support a role for DRD2 in influencing sleep duration. Our work motivates future pharmocogenetics research on alerting agents such as caffeine and modafinil that interact with the dopaminergic pathway and further investigation of genetic overlap between sleep and neuro-psychiatric traits.