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Frontiers in Neurology 2023Hypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This...
INTRODUCTION
Hypnic headache (HH) is a primary headache, and it is considered a rare condition in children. The underlying mechanisms of HH are not yet fully understood. This systematic review aims to provide a comprehensive description of the clinical features of all published cases of pediatric HH. It will also discuss the differences in headache features between children and adults, the increased diagnostic sensitivity of the new diagnostic criteria (ICHD-3), potential pathophysiological hypotheses explaining the higher incidence in adults, differential diagnoses, and therapeutic options for children.
METHODS
A systematic search was conducted to identify and analyze articles reporting cases of HH in patients under the age of 18. The search was performed in major medical databases including Cochrane Library, EBSCO, Embase, Medline, PubMed, Science Direct, Scopus, and Web of Science. The search covered the period from 1988 to April 2023. Relevant studies were screened for eligibility, and data extraction was performed using a standardized approach.
RESULTS
Seven children with HH were included in the analysis. The mean age of onset for headache attacks was 10 ± 4.3 years (range 3-15 years). The average time from the start of headaches to diagnosis was 15.8 ± 25.0 months (range 1-60 months). Headache features in children differed from those observed in adult HH patients. Children experienced throbbing/pulsating pain, while adults reported dull/pressure-like pain. Children also had lower frequency and shorter duration of attacks compared to adults. The use of ICHD-3 criteria appeared to be more sensitive and inclusive for diagnosing HH in children compared to the previous ICHD-2 criteria. The association of headache attacks with sleep suggests that HH may be a primary disorder with a chronobiological origin. Hypothalamic dysfunction and melatonin dysregulation, which are more prevalent in older individuals, could potentially explain the higher incidence of HH in adults. Other primary headaches and secondary causes should be ruled out. Melatonin prophylactic therapy may be considered for pediatric patients.
DISCUSSION
Further evaluation of the clinical features of HH in children is needed. The development of specific diagnostic criteria for pediatric cases could improve diagnostic rates and enhance the management of children with HH.
PubMed: 37638182
DOI: 10.3389/fneur.2023.1254567 -
Journal of Sleep Research Dec 2023Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was... (Meta-Analysis)
Meta-Analysis Review
Melatonin has gained growing interest as a treatment of insomnia, despite contradictory findings, and a low level of evidence. A systematic review and meta-analysis was conducted following PRISMA criteria, to assess the efficacy of melatonin and ramelteon compared with placebo on sleep quantity and quality in insomnia disorder, while also considering factors that may impact their efficacy. This review included 22 studies, with 4875 participants, including 925 patients treated with melatonin, 1804 treated with ramelteon and 2297 receiving a placebo. Most studies evaluated the acute efficacy of prolonged release (PR) melatonin in insomnia disorder. Compared with placebo, PR melatonin appears efficacious with a small to medium effect size on subjective sleep onset latency (sSOL) (p = 0.031; weighted difference = -6.30 min), objective sleep onset latency (oSOL) (p < 0.001; weighted difference = -5.05 min), and objective sleep efficiency (oSE) (p = 0.043; weighted difference = 1.91%). For the subgroup mean age of patients ≥55, PR melatonin was efficacious on oSE with a large effect size (p < 0.001; weighted difference = 2.95%). Ramelteon was efficacious with a large effect size at 4 weeks on objective total sleep time (oTST) (p = 0.010; weighted difference = 17.9 min), subjective total sleep time (sTST) (p = 0.006; weighted difference = 11.7 min), sSOL (p = 0.009; weighted difference = -8.74 min), and oSOL (p = 0.017; weighted difference = -14 min). Regarding long-term effects, ramelteon has a large effect size on oTST (p < 0.001; weighted difference = 2.02 min) and sTST (p < 0.001; weighted difference = 14.5 min). PR melatonin and ramelteon appear efficacious compared with placebo for insomnia symptoms with PR melatonin showing mostly small to medium effect sizes. PR melatonin for individuals with a mean age ≥ 55 and ramelteon show larger effect sizes.
Topics: Humans; Adult; Sleep Initiation and Maintenance Disorders; Sleep; Melatonin; Indenes
PubMed: 37434463
DOI: 10.1111/jsr.13939 -
Frontiers in Endocrinology 2023To determine the preventive effect of melatonin on delirium in the intensive care units. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To determine the preventive effect of melatonin on delirium in the intensive care units.
METHODS
We conducted a systematic search of the PubMed, Cochrane Library, Science, Embase, and CNKI databases, with retrieval dates ranging from the databases' inception to September 2022. Controlled trials on melatonin and placebo for preventing delirium in the intensive care units were included. The meta-analysis was performed using Review Manager software (version 5.3) and Stata software (version 14.0).
RESULTS
Six studies involving 2374 patients were included in the meta-analysis. The results of the meta-analysis showed that melatonin did not reduce the incidence of delirium in ICU patients (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.46 to 1.12; p = 0.14). There was a strong hetero-geneity between the selected studies (I = 74%). Subgroup analysis results showed that melatonin reduced the incidence of delirium in cardiovascular care unit (CCU) patients (OR: 0.52; 95% CI: 0.37 to 0.73; p=0.0001), but did not in general intensive care unit (GICU) patients (OR: 1.14; 95% CI: 0.86 to 1.50; p=0.35). In terms of the secondary outcomes, there were no significant differences in all-cause mortality (OR: 0.85; 95% CI: 0.66 to 1.09; p=0.20), length of ICU stay (mean difference [MD]: 0.33; 95% CI: -0.53 to 1.18; p=0.45), or length of hospital stay (MD: 0.51; 95% CI: -1.17 to 2.19; p=0.55).
CONCLUSION
Melatonin reduced the incidence of delirium in CCU patients, but did not significantly reduce the incidence of delirium in GICU patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42022367665.
Topics: Humans; Melatonin; Delirium; Randomized Controlled Trials as Topic; Intensive Care Units; Length of Stay
PubMed: 37564987
DOI: 10.3389/fendo.2023.1191830 -
Endocrine Feb 2024Melatonin supplementation has been disclosed as an ergogenic substance. However, the effectiveness of melatonin supplementation in healthy subjects has not been... (Meta-Analysis)
Meta-Analysis
PURPOSE
Melatonin supplementation has been disclosed as an ergogenic substance. However, the effectiveness of melatonin supplementation in healthy subjects has not been systematically investigated. The present study analyzed the effects of melatonin supplementation on physical performance and recovery. In addition, it was investigated whether exercise bout or training alter melatonin secretion in athletes and exercise practitioners.
METHODS
This systematic review and meta-analysis were conducted and reported according to the guidelines outlined in the PRISMA statement. Based on the search and inclusion criteria, 21 studies were included in the systematic review, and 19 were included in the meta-analysis.
RESULTS
Melatonin supplementation did not affect aerobic performance relative to time trial (-0.04; 95% CI: -0.51 to 0.44) and relative to VO (0.00; 95% CI: -0.57 to 0.57). Also, melatonin supplementation did not affect strength performance (0.19; 95% CI: -0.28 to 0.65). Only Glutathione Peroxidase (GPx) secretion increased after melatonin supplementation (1.40; 95% CI: 0.29 to 2.51). Post-exercise melatonin secretion was not changed immediately after an exercise session (0.56; 95% CI: -0.29 to 1.41) and 60 min after exercise (0.56; 95% CI: -0.29 to 1.41).
CONCLUSION
The data indicate that melatonin is not an ergogenic hormone. In contrast, melatonin supplementation improves post-exercise recovery, even without altering its secretion.
Topics: Humans; Melatonin; Performance-Enhancing Substances; Dietary Supplements; Exercise; Post-Exercise Recovery
PubMed: 37658244
DOI: 10.1007/s12020-023-03498-1 -
International Journal of Molecular... Oct 2023Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to... (Meta-Analysis)
Meta-Analysis Review
Bisphenols such as bisphenol A (BPA), S (BPS), C (BPC), F (BPF), AF (BPAF), tetrabromobisphenol, nonylphenol, and octylphenol are plasticizers used worldwide to manufacture daily-use articles. Exposure to these compounds is related to many pathologies of public health importance, such as infertility. Using a protector compound against the reproductive toxicological effects of bisphenols is of scientific interest. Melatonin and vitamins have been tested, but the results are not conclusive. To this end, this systematic review and meta-analysis compared the response of reproductive variables to melatonin and vitamin administration as protectors against damage caused by bisphenols. We search for controlled studies of male rats exposed to bisphenols to induce alterations in reproduction, with at least one intervention group receiving melatonin or vitamins (B, C, or E). Also, molecular docking simulations were performed between the androgen (AR) and estrogen receptors (ER), melatonin, and vitamins. About 1234 records were initially found; finally, 13 studies were qualified for review and meta-analysis. Melatonin plus bisphenol improves sperm concentration and viability of sperm and increases testosterone serum levels compared with control groups; however, groups receiving vitamins plus bisphenols had lower sperm concentration, total testis weight, and testosterone serum levels than the control. In the docking analysis, vitamin E had the highest negative MolDock score, representing the best binding affinity with AR and ER, compared with other vitamins and melatonin in the docking. Our findings suggest that vitamins could act as an endocrine disruptor, and melatonin is most effective in protecting against the toxic effects of bisphenols.
Topics: Male; Rats; Animals; Melatonin; Vitamins; Molecular Docking Simulation; Semen; Benzhydryl Compounds; Reproduction; Receptors, Estrogen; Vitamin A; Vitamin K; Testosterone; Endocrine Disruptors
PubMed: 37834378
DOI: 10.3390/ijms241914930 -
Frontiers in Cardiovascular Medicine 2023Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced... (Review)
Review
BACKGROUND
Oxidative stress induced by the excessive production of reactive oxygen species is one of the primary mechanisms implicated in anthracycline (ANT)-induced cardiotoxicity. There is a strong clinical need for a molecule capable of effectively preventing and reducing the oxidative damage caused by ANT. In vitro and studies conducted in mice have shown that melatonin stimulates the expression of antioxidative agents and reduces lipid peroxidation induced by ANT.
METHODS
We investigated this issue through a meta-analysis of murine model studies. The outcome of the meta-analysis was to compare oxidative damage, estimated by products of lipid peroxidation (MDA = Malondialdehyde) and markers of oxidative stress (SOD = Superoxide Dismutase, GSH = Glutathione), along with a marker of cardiac damage (CK-MB = creatine kinase-myocardial band), assessed by measurements in heart and/or blood samples in mice undergoing ANT chemotherapy and assuming melatonin vs. controls. The PubMed, OVID-MEDLINE and Cochrane library databases were analysed to search English-language review papers published from the inception up to August 1st, 2023. Studies were identified by using Me-SH terms and crossing the following terms: "melatonin", "oxidative stress", "lipid peroxidation", "anthracycline", "cardiotoxicity".
RESULTS
The metanalysis included 153 mice administered melatonin before, during or immediately after ANT and 153 controls from 13 studies. Compared with controls, the levels of all oxidative stress markers were significantly better in the pooled melatonin group, with standardized mean differences (SMD) for MDA, GSH and SOD being -8.03 ± 1.2 (CI: -10.43/-5.64, < 0.001), 7.95 ± 1.8 (CI: 4.41/11.5, < 0.001) and 3.94 ± 1.6 (CI: 0.77/7.12, = 0.015) respectively. Similarly, compared with controls, CK-MB levels reflecting myocardial damage were significantly lower in the pooled melatonin group, with an SMD of -4.90 ± 0.5 (CI: -5.82/-3.98, < 0.001).
CONCLUSION
Melatonin mitigates the oxidative damage induced by ANT in mouse model. High-quality human clinical studies are needed to further evaluate the use of melatonin as a preventative/treatment strategy for ANT-induced cardiotoxicity.
PubMed: 38075951
DOI: 10.3389/fcvm.2023.1289384 -
BMC Cancer Sep 2023The relationship between sleep disturbances and lung cancer is complex and bidirectional. This meta-epidemiological study aimed to explore the potential association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The relationship between sleep disturbances and lung cancer is complex and bidirectional. This meta-epidemiological study aimed to explore the potential association between sleep disruption and the risk of pulmonary cancer.
METHODS
We conducted a comprehensive literature search of the PubMed, Embase, Cochrane Library, and Web of Science databases to retrieve relevant studies. We employed the Newcastle-Ottawa Scale to assess the quality of the observational studies. Stata 17.0 was used to synthesize and conduct a meta-analysis of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). We used funnel plot analysis and Egger's regression test to evaluate potential publication bias.
RESULTS
A total of 11 studies were included with 469,691 participants. The methodological quality of the included studies ranged from moderate to high. Compared with 7-8 h of sleep time, short sleep duration was associated with a 13% higher lung cancer risk [OR, 1.13; 95%CI: 1.02-1.25; I = 67.6%; P = 0.018] and long sleep duration with a 22% higher risk [OR, 1.22; 95%CI: 1.12-1.33; I = 6.9%; P < 0.001]. Insomnia symptoms [OR, 1.11; 95%CI: 1.07-1.16; I = 0%; P < 0.001] and evening chronotype [OR, 1.15; 95%CI: 1.05-1.26; P = 0.002] were all related to a higher risk of lung cancer. Egger's test revealed no publication bias for sleep duration (P = 0.13).
DISCUSSION
This systematic review is the first one which observes positive correction between sleep disturbances and the incidence of lung cancer. While the plausible mechanism is not clear, it is hypothesized that the association of short sleep duration and lung cancer mainly mediated by melatonin secretion and the immune-inflammatory balance. Further studies are needed to examine whether other risk factors, such as age, occupation, cumulative effect of sleep disturbances might mediate the relationship between sleep disturbances and lung cancer risk.
CONCLUSION
The present study revealed that insufficient and excessive sleep duration, insomnia symptoms, and evening chronotype were significantly predictive of an increased risk of lung cancer. This finding underscores the need to account for sleep disturbances as an independent risk factor for evaluating susceptibility to lung cancer.
TRIAL REGISTRATION
CRD42023405351.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Lung Neoplasms; Sleep Wake Disorders; Sleep; Epidemiologic Studies
PubMed: 37726707
DOI: 10.1186/s12885-023-11392-2 -
EClinicalMedicine Jul 2023Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use...
Use of melatonin for children and adolescents with chronic insomnia attributable to disorders beyond indication: a systematic review, meta-analysis and clinical recommendation.
BACKGROUND
Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use of melatonin in children and adolescents aged 2-20 years, with chronic insomnia due to disorders beyond indication.
METHODS
We performed a systematic search for guidelines, systematic reviews, and randomised trials (RCTs) in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A separate search for adverse events was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 17, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (2-20 years of age) with chronic insomnia due to underlying disorders, in whom sleep hygiene practices have been inadequate and melatonin was tested. Studies exclusively on autism spectrum disorders or attention deficit hyperactive disorder were excluded. There were no restrictions on dosage, duration of treatment, time of consumption or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events, assessed at 2-4 weeks post-treatment. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, non-serious adverse events, and all-cause dropouts (assessed at 2-4 weeks post-treatment), plus quality of sleep and daytime functioning (assessed at 3-6 months post-treatment). Pooled estimates were calculated using inverse variance random effects model. Statistical heterogeneity was calculated using I statistics. Risk of bias was assessed using Cochrane risk of bias tool. Publication bias was assessed using funnel plots. A multidisciplinary guideline panel constructed the recommendation using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was used to discuss the feasibility and acceptance of the constructed recommendation and its impact on resources and equity. The protocol is registered with the Danish Health Authority.
FINDINGS
We identified 13 RCTs, including 403 patients with a wide range of conditions. Melatonin reduced sleep latency by 14.88 min (95% CI 23.42-6.34, 9 studies, I = 60%) and increased total sleep time by 18.97 min (95% CI 0.37-37.57, 10 studies, I = 57%). The funnel plot for total sleep time showed no apparent indication of publication bias. No other clinical benefits were found. The number of patients experiencing adverse events was not statistically increased however, safety data was scarce. Certainty of evidence was low.
INTERPRETATION
Low certainty evidence supports a moderate effect of melatonin in treating sleep continuity parameters in children and adolescents with chronic insomnia due to primarily medical disorders beyond indication. The off-label use of melatonin for these patients should never be the first choice of treatment, but may be considered by medical specialists with knowledge of the underlying disorder and if non-pharmacological interventions are inadequate. If treatment with melatonin is initiated, adequate follow-up to evaluate treatment effect and adverse events is essential.
FUNDING
The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.
PubMed: 37457114
DOI: 10.1016/j.eclinm.2023.102049 -
EClinicalMedicine Jul 2023Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to...
BACKGROUND
Currently, melatonin is used to treat children and adolescents with insomnia without knowing the full extent of the short-term and long-term consequences. Our aim was to provide clinicians and guideline panels with a systematic assessment of serious-and non-serious adverse events seen in continuation of melatonin treatment and the impact on pubertal development and bone health following long-term administration in children and adolescents with chronic insomnia.
METHODS
We searched PubMed, Embase, Cinahl and PsycINFO via Ovid, up to March 17, 2023, for studies on melatonin treatment among children and adolescents (aged 5-20 years) with chronic insomnia. The language was restricted to English, Danish, Norwegian, and Swedish. Outcomes were non-serious adverse events and serious adverse events assessed 2-4 weeks after initiating treatment and pubertal development and bone health, with no restriction on definition or time of measurement. Observational studies were included for the assessment of long-term outcomes, and serious and non-serious adverse events were assessed via randomised studies. The certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The protocol is registered with the Danish Health Authority.
FINDINGS
We identified 22 randomised studies with 1350 patients reporting on serious-and non-serious adverse events and four observational studies with a total of 105 patients reporting on pubertal development. Melatonin was not associated with serious adverse events, yet the number of patients experiencing non-serious adverse events was increased (Relative risk 1.56, 95% CI 1.01-2.43, 17 studies, I = 47%). Three studies reported little or no influence on pubertal development following 2-4 years of treatment, whereas one study registered a potential delay following longer treatment durations (>7 years). These findings need further evaluation due to several methodological limitations.
INTERPRETATION
Children who use melatonin are likely to experience non-serious adverse events, yet the actual extent to which melatonin leads to non-serious adverse events and the long-term consequences remain uncertain. This major gap of knowledge on safety calls for caution against complacent use of melatonin in children and adolescents with chronic insomnia and for more research to inform clinicians and guideline panels on this key issue.
FUNDING
The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.
PubMed: 37483551
DOI: 10.1016/j.eclinm.2023.102083 -
Indian Journal of Critical Care... Sep 2023Delirium, being a common disorder among critically ill patients, has a reported incidence ranging 45-83% in the intensive care unit (ICU) population. The prophylactic... (Review)
Review
INTRODUCTION
Delirium, being a common disorder among critically ill patients, has a reported incidence ranging 45-83% in the intensive care unit (ICU) population. The prophylactic use of melatonin and melatonergics has been shown to have a positive effect in reducing the incidence of delirium in many clinical trials. Our study was thus proposed to find out the role of melatonin on the incidence and severity of ICU delirium, ICU and hospital length of stay (LOS), requirement, duration of mechanical ventilation, and ICU mortality.
METHODOLOGY
A systematic search of various databases was performed to find out the trials which compare melatonin with a placebo or standard therapy for delirium prevention with the results conveyed as mean differences (MDs) or risk ratios. The statistical software, Review Manager (RevMan, version 5.4), was used for data synthesis.
RESULTS
Twelve studies were included in the meta-analysis. Prophylactic administration of melatonin or ramelteon was not associated with a statistically significant reduction in the incidence of delirium (odds ratio [OR] 0.63; confidence interval [CI]: 0.60, 1.32; = 0.22), the severity of delirium (MD: 0.22; 95% CI: From -1.36 to 1.81; = 0.78), ICU LOS (MD: 0.05; 95% CI: From -0.65 to 0.75; = 0.89), hospital LOS (MD: -1.46; 95% CI: From -4.50 to -1.59; = 0.35), need for mechanical ventilation (OR: 0.74, 95% CI: 0.38-1.44; = 0.37), and ICU mortality (MD: 0.78; 95% CI: 0.56; 1.11; = 0.62). However, a significant reduction in the duration of mechanical ventilation (MD: -0.85; 95% CI: From -1.64 to -0.06; = 0.03) was found.
CONCLUSION
Our meta-analysis suggests that melatonin when given prophylactically has no significant role in reducing the incidence and severity of delirium, ICU and hospital LOS, need for mechanical ventilation, duration of mechanical ventilation, and ICU mortality. Further studies are warranted.
HOW TO CITE THIS ARTICLE
Mukundarajan R, Soni KD, Trikha A. Prophylactic Melatonin for Delirium in Intensive Care Unit: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials. Indian J Crit Care Med 2023;27(9):675-685.
PubMed: 37719343
DOI: 10.5005/jp-journals-10071-24529