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Developmental Medicine and Child... Mar 2024To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE). (Review)
Review
AIM
To review the evidence of the effects of neonatal magnesium sulphate for neuroprotection in perinatal asphyxia and hypoxic-ischaemic encephalopathy (HIE).
METHOD
This was a systematic review of randomized controlled trials (RCTs) (with meta-analysis) and non-RCTs assessing magnesium sulphate for treating perinatal asphyxia and HIE at 35 weeks or more gestation (primary outcomes: neonatal death and death or long-term major neurodevelopmental disability).
RESULTS
Twenty-five RCTs (2099 infants) and four non-RCTs (871 infants) were included, 23 in low- and middle-income countries (LMICs). In RCTs, reductions in neonatal death with magnesium sulphate versus placebo or no treatment (risk ratio [RR] = 0.68; 95% confidence interval [CI] = 0.53-0.86; 13 RCTs), and magnesium sulphate with melatonin versus melatonin alone (RR = 0.74; 95% CI = 0.58-0.95; one RCT) were observed. No difference in neonatal death was seen for magnesium sulphate with therapeutic hypothermia versus therapeutic hypothermia alone (RR = 0.66, 95% CI = 0.34-1.26; three RCTs), or magnesium sulphate versus phenobarbital (RR = 3.00; 95% CI = 0.86-10.46; one RCT). No reduction in death or long-term neurodevelopmental disability (RR = 0.52; 95% CI = 0.14-1.89; one RCT) but reductions in several short-term adverse outcomes were observed with magnesium sulphate. Evidence was low- to very-low certainty because of risk of bias and imprecision.
INTERPRETATION
Given the uncertainty of the current evidence, further robust neonatal magnesium sulphate research is justified. This may include high-quality studies to determine stand-alone effects in LMICs and effects with and after therapeutic hypothermia in high-income countries.
PubMed: 38468452
DOI: 10.1111/dmcn.15899 -
Frontiers in Neurology 2023Since its discovery as an antioxidant, melatonin has been increasingly recognized for its therapeutic potential beyond sleep disturbances in neurodegenerative disorders....
OBJECTIVE
Since its discovery as an antioxidant, melatonin has been increasingly recognized for its therapeutic potential beyond sleep disturbances in neurodegenerative disorders. This study aims to evaluate efficacy of various melatonin doses, treatment durations, and formulations, in alleviating motor symptoms and sleep disturbances in Parkinson's disease, the second most common neurodegenerative disorder worldwide.
METHODS
PubMed, Cochrane Library, ClinicalTrials.gov and other databases were systematically searched to retrieve randomized controlled trials (RCTs) administrating melatonin to Parkinson's disease patients until June 10th, 2023. Outcomes including Unified Parkinson Disease Rating Scale (UPDRS) scores and Pittsburgh Sleep Quality Index (PSQI) scores, were pooled and reported as mean differences (MD) with 95% confidence intervals (CIs). Meta-analysis was performed using an inverse variance random-effects model in Review Manager 5.4 software. Trial Sequential Analysis was performed to avoid false-positive results from random errors.
RESULTS
Five RCTs with a total of 155 patients were included. Statistically significant reductions in UPDRS total scores were observed in groups receiving Melatonin ≥10 mg/day (MD = -11.35, 95% CI: -22.35 to -0.35, I = 0%, = 0.04) and immediate release formulations (MD = -11.35, 95% CI: -22.35 to -0.35, I = 0%, = 0.04). No significant effects on individual UPDRS II, III, and IV scores were observed, regardless of melatonin dosage and treatment duration. Moreover, significant improvements in PSQI scores were observed with only immediate-release melatonin formulations (MD = -2.86, 95% CI: -4.74 to -0.97, I = 0%, = 0.003).
CONCLUSION
Melatonin ≥10 mg/day for a minimum duration of ≥12 weeks in immediate-release formulations consistently demonstrated significant therapeutic potential in improving motor symptom and sleep disturbances in Parkinson disease. However, further trials are warranted to investigate its impact when initiated early in the disease course to fully explore its true therapeutic potential.
SYSTEMATIC REVIEW REGISTRATION
Unique identifier: CRD42023427491 (PROSPERO).
PubMed: 37881313
DOI: 10.3389/fneur.2023.1265789 -
Journal of Pineal Research Dec 2023Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma... (Review)
Review
Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (n = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (n = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (n = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, p = .02), while GCTs and HGG histology well predicted PD (OR: 13, p = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.
Topics: Humans; Pinealoma; Radiosurgery; Brain Neoplasms; Melatonin; Pineal Gland; Glioma; Neoplasms, Germ Cell and Embryonal
PubMed: 37705383
DOI: 10.1111/jpi.12910 -
JNCI Cancer Spectrum Apr 2024Considering the persistent nature and higher prevalence of insomnia in cancer patients and survivors compared with the general population, there is a need for effective... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Considering the persistent nature and higher prevalence of insomnia in cancer patients and survivors compared with the general population, there is a need for effective management strategies. This systematic review and meta-analysis aimed to comprehensively evaluate the available evidence for the efficacy of pharmacological and nonpharmacological interventions for insomnia in adult cancer patients and survivors.
METHODS
Following the PRISMA guidelines, we analyzed data from 61 randomized controlled trials involving 6528 participants. Interventions included pharmacological, physical, and psychological treatments, with a focus on insomnia severity and secondary sleep and non-sleep outcomes. Frequentist and Bayesian analytical strategies were employed for data synthesis and interpretation.
RESULTS
Cognitive-Behavioral Therapy for Insomnia (CBT-I) emerged as the most efficacious intervention for reducing insomnia severity in cancer survivors and further demonstrated significant improvements in fatigue, depressive symptoms, and anxiety. CBT-I showed a large postintervention effect (g = 0.86; 95% confidence interval [CI] = 0.57 to 1.15) and a medium effect at follow-up (g = 0.55; 95% CI = 0.18 to 0.92). Other interventions such as bright white light therapy, sleep medication, melatonin, exercise, mind-body therapies, and mindfulness-based therapies showed benefits, but the evidence for their efficacy was less convincing compared with CBT-I. Brief Behavioral Therapy for Insomnia showed promise as a less burdensome alternative for patients in active cancer treatment.
CONCLUSIONS
CBT-I is supported as a first-line treatment for insomnia in cancer survivors, with significant benefits observed across sleep and non-sleep outcomes. The findings also highlight the potential of less intensive alternatives. The research contributes valuable insights for clinical practice and underscores the need for further exploration into the complexities of sleep disturbances in cancer patients and survivors.
Topics: Adult; Humans; Anxiety; Cancer Survivors; Cognitive Behavioral Therapy; Depression; Exercise Therapy; Fatigue; Hypnotics and Sedatives; Melatonin; Mind-Body Therapies; Mindfulness; Neoplasms; Phototherapy; Sleep Aids, Pharmaceutical; Sleep Initiation and Maintenance Disorders
PubMed: 38781520
DOI: 10.1093/jncics/pkae041 -
Nutrition and Health Mar 2024Type 2 diabetes is a chronic disease that has severe individual and societal consequences, which is forecast to worsen in the future. A new field of investigation is... (Review)
Review
BACKGROUND
Type 2 diabetes is a chronic disease that has severe individual and societal consequences, which is forecast to worsen in the future. A new field of investigation is variations in circadian rhythm genes, in conjunction with diet and sleep variables, associations with, and effects on, type 2 diabetes development.
OBJECTIVE
This systematic review aimed to analyse all current literature regarding circadian rhythm gene variations and type 2 diabetes, and explore their interplay with diet and sleep variables on type 2 diabetes outcomes. This review was registered with PROSPERO (CRD42021259682).
METHODOLOGY
Embase and Pubmed were searched on 6/8/2021/11/8/2021 for studies of all designs, including participants from both sexes, all ethnicities, ages, and geographic locations. Participants with risk alleles/genotypes were compared with the wildtype regarding type 2 diabetes outcomes. Studies risk of bias were scored according to the risk of bias in non-randomised studies - interventions/exposures criteria.
RESULTS
In total, 31 studies were found (association = 29/intervention = 2) including >600,000 participants from various ethnicities, sexes, and ages. Variations in the melatonin receptor 1B, brain and muscle arnt-like 1 and period circadian regulator (PER) genes were consistently associated with type 2 diabetes outcomes.
CONCLUSIONS
Individuals with variations in melatonin receptor 1B, brain and muscle arnt-like 1 and PER may be at higher risk of type 2 diabetes. Further research is needed regarding other circadian rhythm genes. More longitudinal studies and randomised trials are required before clinical recommendations can be made.
Topics: Male; Female; Humans; Diabetes Mellitus, Type 2; Melatonin; Receptors, Melatonin; Circadian Rhythm; Sleep
PubMed: 37282546
DOI: 10.1177/02601060231179777 -
Journal of Intensive Care Medicine Jun 2024Patients in the intensive care unit (ICU) often experience poor sleep quality. Pharmacologic sleep aids are frequently used as primary or adjunctive therapy to improve... (Review)
Review
Patients in the intensive care unit (ICU) often experience poor sleep quality. Pharmacologic sleep aids are frequently used as primary or adjunctive therapy to improve sleep, although their benefits in the ICU remain uncertain. This review aims to provide a comprehensive assessment of the objective and subjective effects of medications used for sleep in the ICU, as well as their adverse effects. PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials were systematically searched from their inception until June 2023 for comparative studies assessing the effects of pharmacologic sleep aids on objective and subjective metrics of sleep. Thirty-four studies with 3498 participants were included. Medications evaluated were melatonin, ramelteon, suvorexant, propofol, and dexmedetomidine. The majority of studies were randomized controlled trials. Melatonin and dexmedetomidine were the best studied agents. Objective sleep metrics included polysomnography (PSG), electroencephalography (EEG), bispectral index, and actigraphy. Subjective outcome measures included patient questionnaires and nursing observations. Evidence for melatonin as a sleep aid in the ICU was mixed but largely not supportive for improving sleep. Evidence for ramelteon, suvorexant, and propofol was too limited to offer definitive recommendations. Both objective and subjective data supported dexmedetomidine as an effective sleep aid in the ICU, with PSG/EEG in 303 ICU patients demonstrating increased sleep duration and efficiency, decreased arousal index, decreased percentage of stage N1 sleep, and increased absolute and percentage of stage N2 sleep. Mild bradycardia and hypotension were reported as side effects of dexmedetomidine, whereas the other medications were reported to be safe. Several ongoing studies have not yet been published, mostly on melatonin and dexmedetomidine. While definitive conclusions cannot be made for most medications, dexmedetomidine improved sleep quantity and quality in the ICU. These benefits need to be balanced with possible hemodynamic side effects.
PubMed: 38881385
DOI: 10.1177/08850666241255345 -
The Journal of International Medical... May 2024To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and safety of perioperative melatonin and melatonin agonists in preventing postoperative delirium (POD).
METHODS
We conducted a systematic search for randomized controlled trials (RCTs) published through December 2022. The primary outcome was efficacy based on the incidence of POD (POD-I). Secondary outcomes included efficacy and safety according to the length of hospital or intensive care unit stay, in-hospital mortality, and adverse events. Subgroup analyses of POD-I were based on the type and dose of drug (low- and high-dose melatonin, ramelteon), the postoperative period (early or late), and the type of surgery.
RESULTS
In the analysis (16 RCTs, 1981 patients), POD-I was lower in the treatment group than in the control group (risk ratio [RR] = 0.57). POD-I was lower in the high-dose melatonin group than in the control group (RR = 0.41), whereas no benefit was observed in the low-dose melatonin and ramelteon groups. POD-I was lower in the melatonin group in the early postoperative period (RR = 0.35) and in patients undergoing cardiopulmonary surgery (RR = 0.54).
CONCLUSION
Perioperative melatonin or melatonin agonist treatment suppressed POD without severe adverse events, particularly at higher doses, during the early postoperative period, and after cardiopulmonary surgery.
Topics: Melatonin; Humans; Postoperative Complications; Delirium; Perioperative Care; Indenes; Randomized Controlled Trials as Topic; Length of Stay; Treatment Outcome; Hospital Mortality
PubMed: 38735057
DOI: 10.1177/03000605241239854 -
Neuroscience and Biobehavioral Reviews Feb 2024Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural... (Review)
Review
BACKGROUND
Cancer survivors frequently experience cognitive impairments. This systematic review assessed animal literature to identify artificial (pharmaceutical) or natural interventions (plant/endogenously-derived) to reduce treatment-related cognitive impairments.
METHODS
PubMed, EMBASE, PsycINFO, Web of Science, and Scopus were searched and SYRCLE's tool was used for risk of bias assessment of the 134 included articles.
RESULTS
High variability was observed and risk of bias analysis showed overall poor quality of reporting. Results generally showed positive effects in the intervention group versus cancer-therapy only group (67% of 156 cognitive measures), with only 15 (7%) measures reporting cognitive impairment despite intervention. Both artificial (61%) and natural (75%) interventions prevented cognitive impairment. Artificial interventions involving GSK3B inhibitors, PLX5622, and NMDA receptor antagonists, and natural interventions utilizing melatonin, curcumin, and N-acetylcysteine, showed most consistent outcomes.
CONCLUSIONS
Both artificial and natural interventions may prevent cognitive impairment in rodents, which merit consideration in future clinical trials. Greater consistency in design is needed to enhance the generalizability across studies, including timing of cognitive tests and description of treatments and interventions.
Topics: Humans; Animals; Cognitive Dysfunction; Cancer Survivors
PubMed: 38135266
DOI: 10.1016/j.neubiorev.2023.105514 -
Obstetrics & Gynecology Science Mar 2024This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain...
The effect of antioxidant supplementation on dysmenorrhea and endometriosis-associated painful symptoms: a systematic review and meta-analysis of randomized clinical trials.
This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain symptoms. The PubMed/Medline, Scopus, and Web of Science databases were searched until April 2022. Additionally, we manually searched the reference lists. Endpoints were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) in a random-effects model. The I2 statistic was used to assess heterogeneity. Ten RCTs were included in this meta-analysis. Overall, 10 studies were related to dysmenorrhea, four to dyspareunia, and four to pelvic pain. Antioxidants significantly reduced dysmenorrhea (SMD, -0.48; 95% CI, -0.82 to -0.13; I2=75.14%). In a subgroup analysis, a significant reduction of dysmenorrhea was observed only in a subset of trials that administered vitamin D (SMD, -0.59; 95% CI, -1.13 to -0.06; I2=69.59%) and melatonin (SMD, -1.40; 95% CI, -2.47 to -0.32; I2=79.15%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, -1.51; 95% CI, -2.74 to -0.29; I2=93.96%), although they seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea (with an emphasis on vitamin D and melatonin) and pelvic pain. However, due to the relatively small sample size and high heterogeneity, the findings should be interpreted cautiously, and the importance of further well-designed clinical studies cannot be overstated.
PubMed: 38221738
DOI: 10.5468/ogs.23210 -
Brain Research Oct 2023Light is detected in the eye by three classes of photoreceptors (rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs)) that are each optimized... (Meta-Analysis)
Meta-Analysis Review
Light is detected in the eye by three classes of photoreceptors (rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs)) that are each optimized for a specific function and express a particular light-detecting photopigment. The significant role of short-wavelength light and ipRGCs in improving alertness has been well-established; however, few reviews have been undertaken to assess the other wavelengths' effects regarding timing and intensity. This study aims to evaluate the impact of different narrowband light wavelengths on subjective and objective alertness among the 36 studies included in this systematic review, 17 of which were meta-analyzed. Short-wavelength light (∼460-480 nm) significantly improves subjective alertness, cognitive function, and neurological brain activities at night, even for a sustained period (∼6h) (for λmax: 470/475 nm, 0.4 < |Hedges's g| < 0.6, p < 0.05), but except early morning, it almost does not show this effect during the day when melatonin level is lowest. Long-wavelength light (∼600-640 nm) has little effect at night, but significantly increases several measures of alertness at lower irradiance during the daytime (∼1h), particularly when there is homeostatic sleep drive (for λmax: ∼630 nm, 0.5 < |Hedges's g| < 0.8, p < 0.05). The results further suggest that melanopic illuminance may not always be sufficient to measure the alerting effect of light.
Topics: Circadian Rhythm; Sleep; Retinal Cone Photoreceptor Cells; Retinal Ganglion Cells; Retinal Rod Photoreceptor Cells
PubMed: 37364848
DOI: 10.1016/j.brainres.2023.148470