Effects of chronic daily headache with subclinical depression on brain volume: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The relationship between chronic daily headache (CDH), depression symptoms, and brain volume remains unclear. METHODS: To investigate the effects of CDH on brain volume and the impact of depressive symptoms (DSs) as well as the effects of demography and medication overuse, PubMed, Embase, and Web of Science databases were systematically searched using appropriate keyword strings to retrieve observational studies from inception to May 2023. RESULTS: Two distinct comparisons were made in CDH patients: (1) those with DSs versus their pain-free counterparts and (2) those without DSs versus pain-free controls. The first comprised nine studies enrolling 225 CDH patients with DSs and 234 controls. Beck depression inventory, Hamilton depression scale, and Hospital anxiety/depression scale were used to assess DSs, revealing significantly more DSs in CDH patients with DSs compared to their controls (all p < 0.05). Besides, the second analysed four studies involving 117 CDH patients without DSs and 155 comparators. Compared to CDH patients without DSs, those with DSs had a smaller brain volume than controls (p = 0.03). Furthermore, CDH patients with DSs who did not overuse medications showed a smaller right cerebral cortical volume than overusers (p = 0.003). A significant inverse correlation between female prevalence and brain volume (p = 0.02) was revealed using regression analysis. CONCLUSIONS: Pain-induced persistent depressive symptoms not only incur structural alterations but also encompass affective-motivational changes, involving medication use and gender-specific health concerns. SIGNIFICANCE: This study highlighted the importance of an integrated CDH treatment, emphasizing psychological interventions for the affective-motivational component alongside pain management.

Risk of CKD among patients with DM taking diuretics or SGLT2i: a retrospective cohort study in Taiwan.

BACKGROUND: This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. METHODS: We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. RESULTS: The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68-3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32-0.63; aHR, 0.26, 95% CI, 0.17-0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36-0.94) than the both SGLT2i and diuretics group. CONCLUSION: This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.

Collagen patch cover facilitates recovery of bowel function after laparoscopic colectomy.

BACKGROUND: Numerous factors can influence bowel movement recovery and anastomotic healing in colorectal surgery, and poor healing can lead to severe complications and increased medical expenses. Collagen patch cover (CPC) is a promising biomaterial that has been demonstrated to be safe in animal models and has been successfully applied in various surgical procedures in humans. This study. METHODS: A retrospective review of medical records from July 2020 to June 2022 was conducted to identify consecutive patients who underwent laparoscopic colectomy. Patients who received CPC at the anastomotic site were assigned to the collagen group, whereas those who did not receive CPC were assigned to the control group. RESULTS: Data from 241 patients (collagen group, 109; control group, 132) were analyzed. Relative to the control group, the collagen group exhibited a faster recovery of bowel function, including an earlier onset of first flatus (2.93 days vs. 3.43 days, p < 0.01), first defecation (3.73 days vs. 4.18 days, p = 0.01), and oral intake (4.30 days vs. 4.68 days, p = 0.04). CPC use was also associated with lower use of postoperative intravenous analgesics. The complication rates in the two groups did not differ significantly. CONCLUSIONS: CPCs can be safely and easily applied to the anastomotic site during laparoscopic colectomy, and can accelerate bowel movement recovery. Further studies on the effectiveness of CPCs in colorectal surgery involving larger sample sizes are required. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT05831956 (26/04/2023).

A systematic review and meta-analysis of the relationship between heavy smoking and probability discounting.

BACKGROUND AND OBJECTIVES: Probability discounting (PD), which refers to the process of adjusting the value of future probabilities when making decisions, is a method of measuring impulsive decision-making; however, the relationship between PD and nicotine remains unclear. The current study aimed at investigating the significance of PD in individuals who smoke. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, PsycINFO, and Web of Science databases for articles comparing individuals who smoke and their tobacco-naïve controls using PD task as outcome measure from inception to May 2023. The main outcome was an overall difference in PD function, while subgroup analysis and meta-regression were conducted to examine the analysis methods and the moderators of PD. RESULTS: Fourteen studies in total involving 384 individuals who smoke and 493 controls (mean age = 24.32 years, range = 15.1-38.05 years) were analyzed. The effect of smoking on PD was significant (g = 0.51, p = .02). The discounting parameter from the equation, compared to the area under the curve, was more sensitive to estimating PD function (p = .01). Regression analysis showed positive correlations of PD with female percentage, age, and the number of probability options (all p < .04), but not with the number of choices at each probability and maximum reward magnitude (all p > .07). There was no significant publication bias across the eligible studies (p = .09). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Our findings, which are the first to demonstrate a smaller PD (i.e., prone to risk-taking) in individuals who smoke, shed light on the appropriate analysis method, gender effect, age, and probability options on the PD function.

Prophylaxis for paediatric emergence delirium in desflurane-based anaesthesia: a network meta-analysis.

PURPOSE: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia. METHODS: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia. RESULTS: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied. CONCLUSIONS: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted. TRIAL REGISTRATION: PROSPERO CRD42021285200.

Zellweger syndrome caused by PEX6 gene variation in 2 cases and literature review / 中华儿科杂志

Objective: To summarize the clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation. Methods: This was a case series research. Clinical date and genetic results of 2 neonatal cases of Zellweger syndrome caused by PEX6 gene variation in Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology and Affiliated Hospital of Guangdong Medical University from July 2021 to July 2022 were retrospectively collected and analyzed. Literature up to August 2023 was searched from electronic databases of China National Knowledge Infrastructure (CNKI), Wanfang Data and PubMed with the combined keywords of "Zellweger syndrome" "Zellweger spectrum disorder", and "PEX6 gene" both in Chinese and English. The main clinical features and genetic characteristics of Zellweger spectrum disorder caused by PEX6 gene variation were summarized. Results: The 2 male neonates both developed clinical manifestations as dyspnea, hypotonia, feeding difficulties, enlarged fontanelle, and high palatine arch after birth. Biochemical parameters indicated elevated bile acids, and the cranial ultrasound showed the enlarged bilateral ventricles and subependymal cyst in both 2 neonates. Zellweger syndrome was confirmed by whole exome sequencing, and the results revealed PEX6 gene variation in the 2 neonates, including compound heterozygous variants c.315G>A and c.2095-3T>G, and homozygous variant c.506_507del. Case 1 was hospitalized for 5 days, and case 2 for 32 days; they both died shortly after being discharged (the specific time is unknown). Literature review found 26 patients, including 2 neonates in this study, with Zellweger spectrum disorder caused by PEX6 gene defect reported in 1 Chinese article and 11 English articles. Clinical features included hearing loss (19 cases), developmental delay (19 cases), vision impairment (19 cases), elevated very long chain fatty acids (17 cases), brain malformations (15 cases), hypotonia (12 cases), hepatic insufficiency (12 cases), distinctive facies (10 cases), and dental impairment (9 cases). Compound heterozygous variations dominated the variation types (15 cases), and the frameshift variations (16 cases) were the main pathogenic variations. Conclusions: Zellweger spectrum disorder should be considered when neonates show hypotonia, feeding difficulty, distinctive facial appearance, brain malformations and failure of hearing screening, or when older children show retinitis pigmentosa, sensorineural hearing loss, amelogenesis imperfecta and developmental delays. Detection of genetic variation in the PEX gene is crucial for definitive diagnosis.

Efficacy and acceptability of anti-inflammatory eicosapentaenoic acid for cognitive function in Alzheimer's dementia: A network meta-analysis of randomized, placebo-controlled trials with omega-3 fatty acids and FDA-approved pharmacotherapy.

Alzheimer's dementia (AD) is a major contributor to global disability, and effective therapies to modify disease progression are currently lacking. The neuro-inflammatory theory is a potential etiology underlying this neurodegenerative disease. Previous randomized, controlled trials (RCTs) have provided inconclusive results regarding efficacy of omega-3 polyunsaturated fatty acids (PUFAs) regimens, which might provide anti-inflammatory benefits in the management of AD, in improving cognitive function among participants with AD. The objective of this frequentist-model based network meta-analysis (NMA) was to evaluate the potential advantages of omega-3 PUFAs and currently FDA-approved medications for AD on overall cognitive function in AD individuals. The primary outcomes were: (1) changes in cognitive function, and (2) acceptability, which refers to all-cause discontinuation. Additionally, secondary outcomes included quality of life, behavioral disturbances and safety/tolerability, which was assessed through the frequency of any reported adverse event. This NMA included 52 RCTs (6 with omega-3 PUFAs and 46 with FDA-approved medications) involving 21,111 participants. The results showed that long-term high-dose (1500-2000 mg/day) of eicosapentaenoic acid (EPA)-dominant omega-3 PUFAs augmented with anti-oxidants had the highest potential for cognitive improvement among all investigated treatments [standardized mean difference = 3.00, 95% confidence intervals (95 %CIs) = 1.84-4.16]. Compared to placebo, omega-3 PUFAs had similar acceptability [odds ratio (OR) = 0.46, 95 %CIs = 0.04 to 5.87] and safety profiles (OR = 1.24, 95 %CIs = 0.66 to 2.33)o. These findings support the potential neurotherapeutic effects of high dosage EPA-dominant omega-3 PUFAs for the amelioration of cognitive decline in patients with AD. Future large-scale, long-term RCTs should focus on different dosages of EPA-dominant omega-3 PUFAs regimens on improving cognitive dysfunction in patients with AD at different levels of inflammatory status and psychopathology.

Meta-analysis reveals a reduced surface area of the amygdala in individuals with attention deficit/hyperactivity disorder.

Despite the reported lack of structural alterations in the amygdala of individuals with attention deficit/hyperactivity disorder (ADHD) in previous meta-analyses, subsequent observational studies produced conflicting results. Through incorporating the updated data from observational studies on structural features of the amygdala in ADHD, the primary goal of this study was to examine the anatomical differences in amygdala between subjects with ADHD and their neurotypical controls. Using the appropriate keyword strings, we searched the PubMed, Embase, and Web of Science databases for English articles from inception to February 2022. Eligibility criteria included observational studies comparing the structure of the amygdala between ADHD subjects and their comparators using magnetic resonance imaging (MRI). Subgroup analyses were conducted focusing on the amygdala side, as well as the use of different scanners and approach to segmentation. The effects of other continuous variables, such as age, intelligence quotient, and male percentage, on amygdala size were also investigated. Of the 5703 participants in 16 eligible studies, 2928 were diagnosed with ADHD. Compared with neurotypical controls, subjects with ADHD had a smaller amygdala surface area (particularly in the left hemisphere) but without a significant difference in volume between the two groups. Subgroup analysis of MRI scanners and different approaches to segmentation showed no statistically significant difference. There was no significant correlation between continuous variables and amygdala size. Our results showed consistent surface morphological alterations of the amygdala, in particular on the left side, in subjects with ADHD. However, the preliminary findings based on the limited data available for analysis warrant future studies for verification.

Cancer related fatigue-light therapy: updated meta-analysis of randomised controlled trials.

BACKGROUND: Moderate-to-severe cancer related fatigue occurs in 45% of patients with cancer and interferes with many aspects of quality of life. Although physical exercise has level 1 evidence for improvement of cancer related fatigue, it has a relatively high behavioural demand compared with other non-pharmacological interventions. The aim of this updated meta-analysis was to address the efficacy of light therapy in improving cancer related fatigue in patients with cancer. METHODS: We included randomised controlled trials investigating the efficacy of bright white light (BWL) therapy in ameliorating cancer related fatigue in patients with cancer. This meta-analysis was conducted using a random-effects model. The target outcomes were changes in cancer related fatigue associated with BWL or dim red light (DRL). RESULTS: There were 9 articles with 231 participants included. The main results revealed that daily morning BWL for 30 min was associated with significantly better improvement in fatigue severity compared with DRL (k=5, Hedges' g=-0.414, 95% CI -0.740 to -0.087, p=0.013). The subgroup without psychiatric comorbidities (k=4, Hedges' g=-0.479, 95% CI -0.801 to -0.156, p=0.004) was associated with significantly better improvement in fatigue severity with BWL than with DRL. In contrary, BWL was not associated with significantly different changes in depression severity or quality of life compared with DRL. Finally, BWL was associated with similar acceptability (ie, dropout rate) and safety profile (ie, any discomfort) as those of DRL. CONCLUSIONS: This meta-analysis provides an updated evidence on the rationale for application of BWL in ameliorating cancer related fatigue in patients with different types of cancer. TRIAL REGISTRATION NUMBER: INPLASY202140090.

Size Reduction of the Right Amygdala in Chronic Pain Patients with Emotional Stress: A Systematic Review and Meta-Analysis.

The structural impact of chronic pain on amygdala in chronic pain (CP) patients remains unclear, although major depression and anxiety are known to be associated with its increase and decrease in size, respectively. This study aimed at examining the relationship between emotional stress and amygdala size in CP patients. The effects of mediating and moderating variables were also examined. The PubMed, Embase, and Web of Science databases were searched for English clinical trials from inception to February 2022 using the appropriate keyword strings. We compared the differences in amygdala size assessed with magnetic resonance imaging between CP patients with emotional stress and healthy counterparts. Of the 49 full-text articles identified, 13 studies enrolling 1,551 participants including 738 CP patients with emotional stress and 813 controls were analyzed. Emotional stress evaluated with questionnaires based on Beck depression inventory, Hamilton depression/anxiety scale, state-trait anxiety inventory, and hospital anxiety and depression scale revealed significant differences between CP patients with emotional stress and controls, indicating a subclinical but significant level of emotional stress in CP patients. The results demonstrated an amygdala shrinkage among CP patients with emotional stress compared to the controls, especially the right side (P = .02). Besides, pain from a single body region was more likely to impact the amygdala size compared to diffuse pain (P = .02). Regression analysis revealed no significant association between continuous variables (age, gender, pain duration/intensity) and amygdala size. Our findings demonstrated that emotional stress was associated with a reduced right amygdala size in CP patients.

The efficacy of exogenous melatonin supplement in ameliorating irritable bowel syndrome severity: A meta-analysis of randomized controlled trials.

BACKGROUND: Irritable bowel syndrome (IBS) was found in 11% of the general population worldwide. The current pharmacologic management of IBS was unsatisfactory, and it was accompanied by a number of adverse events. Melatonin was found to play an important role in gastrointestinal smooth muscle motility. Dysregulation of endogenous melatonin secretion has been found in IBS patients. Exogenous melatonin supplement has become one alternative treatment for IBS, but the evidence is inconclusive. The current meta-analysis sought to determine the efficacy of exogenous melatonin supplement in improving IBS severity in IBS patients. METHODS: We included randomized controlled trials (RCTs) that investigated the efficacy of exogenous melatonin supplement in ameliorating IBS severity in IBS patients. This meta-analysis was conducted using a random effects model. The primary target outcomes were changes in IBS severity associated with melatonin or placebo. RESULTS: This meta-analysis of 4 RCTs and 115 participants revealed that exogenous melatonin supplement was associated with significantly better improvement in overall IBS severity than placebo (k = 4, Hedges' g = 0.746, 95% confidence intervals = 0.401-1.091, p < 0.001). The subgroup without concurrent medication had the same result (p < 0.001). In addition, exogenous melatonin supplement was also associated with significantly better improvement in IBS pain severity (p < 0.001) and quality of life (p = 0.007) than placebo, but not in abdominal distension (p = 0.111) or sleep quality (p = 0.142). Finally, melatonin was associated with similar safety profiles with placebo. CONCLUSION: This meta-analysis provides evidence for the use of exogenous melatonin in IBS patients to ameliorate overall IBS severity, IBS pain severity, and quality of life. TRIAL REGISTRATION: PROSPERO CRD42021269451.

Structural and Functional Neural Correlates in Individuals with Excessive Smartphone Use: A Systematic Review and Meta-Analysis.

Background: Despite known association of internet addiction with a reduced brain volume and abnormal connectivity, the impact of excessive smartphone use remains unclear. Methods: PubMed, Embase, ClinicalTrial.gov, and Web of Science databases were systematically searched from inception to July 2022 using appropriate keywords for observational studies comparing differences in brain volumes and activations between excessive smartphone users and individuals with regular use by magnetic resonance imaging. Results: Of the 11 eligible studies retrieved from 6993 articles initially screened, seven and six evaluated brain volumes and activations, respectively. The former enrolled 421 participants (165 excessive smartphone users vs. 256 controls), while the latter recruited 276 subjects with 139 excessive smartphone users. The results demonstrated a smaller brain volume in excessive smartphone users compared to the controls (g = −0.55, p < 0.001), especially in subcortical regions (p < 0.001). Besides, the impact was more pronounced in adolescents than in adults (p < 0.001). Regression analysis revealed a significant positive association between impulsivity and volume reduction. Regarding altered activations, the convergences of foci in the declive of the posterior lobe of cerebellum, the lingual gyrus, and the middle frontal gyrus were noted. Conclusions: Our findings demonstrated a potential association of excessive smartphone use with a reduced brain volume and altered activations.

Surface electroencephalographic neurofeedback improves sustained attention in ADHD: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of surface electroencephalographic neurofeedback (EEG-NF) for improving attentional performance assessed by laboratory measures in patients with attention-deficit/hyperactivity disorder (ADHD) remains unclear. METHODS: Following the PRISMA guidelines, the PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials on the efficacy of surface EEG-NF against ADHD focusing on attentional performance evaluated by laboratory measures from inception to January 2022. RESULTS: Fourteen eligible studies were analyzed. Of the 718 participants involved, 429 diagnosed with ADHD received EEG-NF treatment. Significant improvement in attentional performance in ADHD subjects receiving EEG-NF was noted compared to their comparators (p < 0.01). Besides, there was a significant EEG-NF-associated beneficial effect on sustained attention (Hedges' g = 0.32, p < 0.01), whereas the impact on selective attention (p = 0.57) and working memory (p = 0.59) was limited. Moreover, protocol including beta wave enhancement was superior to that only focusing on reducing theta/beta ratio or modulation of slow cortical potential. Subgroup analyses showed that three sessions per week of EEG-NF produced the best effect, while the efficacy of surface EEG-NF was much poorer (Hedges' g = 0.05) when only studies that blinded their participants from knowledge of treatment allocation were included. No significant difference was noted in the improvement of attentional performance 6-12 months after EEG-NF intervention (n = 3, p = 0.42). CONCLUSIONS: Our results demonstrated the satisfactory effectiveness of surface EEG-NF for improving sustained attention, especially when beta wave enhancement was included, despite its failure to sustain a long-term effect. Further large-scale trials are warranted to support our findings.

Therapeutic effects of antidepressants for global improvement and subdomain symptoms of autism spectrum disorder: a systematic review and meta-analysis.

BACKGROUND: No established pharmacological treatment is available for the core symptoms of autism spectrum disorder (ASD). This study aimed at investigating the efficacy of antidepressants for the core and associated symptoms of ASD. METHODS: We searched PubMed, Embase, ClinicalKey, Cochrane CENTRAL, ScienceDirect, Web of Science and ClinicalTrials.gov using the keywords "ASD" and "antidepressants." We searched from database inception to June 2021 for randomized controlled trials of antidepressant use in patients with ASD. We calculated pooled effect sizes based on a random-effects model. RESULTS: Analysis of 16 studies with 899 participants showed improvements in restricted and repetitive behaviours (effect size = 0.27) and global symptoms (effect size = 1.0) in patients with ASD taking antidepressants versus those taking placebos (p ≤ 0.01). We found no differences between the 2 groups (p ≥ 0.36) in terms of dropout rate (odds ratio [OR] = 1.17) or rate of study discontinuation because of adverse events (OR = 1.05). We also noted improvements in irritability and hyperactivity in the antidepressant group (Hedges g = 0.33 and 0.22, respectively, both p < 0.03). Subgroup analyses showed significant effects of medication type (i.e., clomipramine was better than SSRIs) and age (antidepressants were more effective in adults than in children or adolescents) on both restricted and repetitive behaviours and global improvement (p < 0.05). Meta-regression demonstrated that better therapeutic effects were associated with lower symptom severity and older age. LIMITATIONS: The small effect sizes and variations in treatment response that we found warrant further study. CONCLUSION: Our results supported the effectiveness of antidepressants for global symptoms and symptom subdomains of ASD, with tolerable adverse effects. Low symptom severity and adulthood were associated with better outcomes.

Changes in Periodic Limb Movements of Sleep After the Use of Continuous Positive Airway Pressure Therapy: A Meta-Analysis.

Background: Both obstructive sleep apnea (OSA) and periodic limb movements of sleep (PLMS) are common in the sleep laboratory. The severity of OSA can be improved by using continuous positive airway pressure (CPAP). However, increasing evidence has shown an elevated periodic limb movement index (PLMI) in patients with OSA who use CPAP, although the pathophysiology is still unknown. This meta-analysis aimed to investigate changes in PLMS after using CPAP and the potential pathophysiology of these changes. Methods: Clinical trials in adult humans investigating the comorbidity between PLMS and CPAP were identified and analyzed using random-effects model meta-analysis. Results: This meta-analysis included 14 studies comprising 2,938 patients with OSA. The PLMI was significantly increased after using CPAP with a difference in means of 1.894 (95% confidence interval = 0.651-3.138, p = 0.003). Subgroup analysis showed that CPAP was only significantly associated with an increase in PLMI in the patients without PLMS at baseline (p = 0.045) and in those with a baseline body-mass index <30 kg/m2 (p = 0.045). The use of CPAP, apnea-hypopnea index, and arousal index were positively correlated with changes in PLMI. Conclusion: These characteristics may serve as qualitative predictive indicators of changes in PLMI after CPAP usage. Further analysis of the quantitative relationships between PLMI and the predictive indicators may be warranted. Trial Registration: PROSPERO (registration number: CRD42021252635).

The Dose and Duration-dependent Association between Melatonin Treatment and Overall Cognition in Alzheimer's Dementia: A Network Meta- Analysis of Randomized Placebo-Controlled Trials.

BACKGROUND: While Alzheimer's dementia (AD) has a prevalence as high as 3-32% and is associated with cognitive dysfunction and the risk of institutionalization, no efficacious and acceptable treatments can modify the course of cognitive decline in AD. Potential benefits of exogenous melatonin for cognition have been divergent across trials. OBJECTIVE: The current network meta-analysis (NMA) was conducted under the frequentist model to evaluate the potential beneficial effects of exogenous melatonin supplementation on overall cognitive function in participants with AD in comparison to other FDA-approved medications (donepezil, galantamine, rivastigmine, memantine, and Namzaric). METHODS: The primary outcome was the changes in the cognitive function [measured by mini-mental state examination (MMSE)] after treatment in patients with Alzheimer's dementia. The secondary outcomes were changes in the quality of life, behavioral disturbance, and acceptability (i.e., drop-out due to any reason and rate of any adverse event reported). RESULTS: The current NMA of 50 randomized placebo-controlled trials (RCTs) revealed the medium-term lowdose melatonin to be associated with the highest post-treatment MMSE (mean difference = 1.48 in MMSE score, 95% confidence intervals [95% CIs] = 0.51 to 2.46) and quality of life (standardized mean difference = -0.64, 95% CIs = -1.13 to -0.15) among all of the investigated medications in the participants with AD. Finally, all of the investigated exogenous melatonin supplements were associated with similar acceptability as was the placebo. CONCLUSION: The current NMA provides evidence for the potential benefits of exogenous melatonin supplementation, especially medium-term low-dose melatonin, in participants with AD.

Pharmacologic interventions for Kawasaki disease in children: A network meta-analysis of 56 randomized controlled trials.

BACKGROUND: Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of the current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial and refractory stages of KD. METHODS: An NMA of randomised controlled trials (RCTs) was conducted using the frequentist model applied after electronic searches in PubMed, Embase, ScienceDirect, ProQuest, ClinicalTrials.gov, ClinicalKey, Cochrane CENTRAL, and Web of Science. The main outcomes were reduced fever duration/diminished severity of fever subsided. The initial stage of KD was defined as the first stage to treat patients with KD; the refractory stage of KD represents KD patients who failed to respond to standard KD treatment. The cut-off points for intravenous immunoglobulin (IVIG) were low (100-400 mg), medium (1 g), and high (at least 2 g). FINDINGS: A total of fifty-six RCTs with 6486 participants were included. NMA demonstrated that the medium-dosage IVIG + aspirin + infliximab [mean difference=-1.76 days (95% confidence intervals (95% CIs): -3.65 to 0.13 days) compared to high-dosage IVIG + aspirin] exhibited the shortest fever duration; likewise, the medium-dosage IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95% CIs: 0.18-1.37 compared to high-dosage IVIG + aspirin] exhibited the smallest incidence of coronary artery lesion (CAL) in the initial-stage KD. In the refractory-stage KD, the high-dosage IVIG + pulse steroid therapy (OR=0.04, 95% CIs: 0.00-0.43 compared to the high-dosage IVIG only) had the best rate of decline of fever; likewise, the high-dosage IVIG + ciclosporin [OR=0.05 (95% CIs: 0.00-1.21) compared to the high-dosage IVIG only] exhibited the smallest incidence of CAL. Infliximab significantly improved resolution compared to the high-dosage IVIG only group (OR=0.20, 95%CIs: 0.07-0.62) in refractory-stage KD. INTERPRETATION: The NMA demonstrated that the combination therapy with the standard therapy of IVIG and aspirin might have an additional effect on shortening the duration of fever and lowering the CAL incidence rate in patients with acute KD. Moreover, the combination therapy with high-dose IVIG and pulse steroid therapy or cyclosporine therapy might have an additional effect on improving the rate of decline of fever and lowering the incidence rate of CAL in children with refractory KD. Because some of the findings of this NMA should be considered hypothesis-generating rather than confirmatory, further evidence from de novo randomised trials is needed to support our results. FUNDING: None.

Comparative transcriptome analysis reveals ectopic delta-5 and delta-6 desaturases enhance protective gene expression upon Vibrio vulnificus challenge in Tilapia (Oreochromis niloticus).

BACKGROUND: Tilapia (Oreochromis niloticus) cultures are frequently infected by Vibrio vulnificus, causing major economic losses to production units. Previously, tilapia expressing recombinant delta-5 desaturase and delta-6 desaturase (D56) were found to be resistant to V. vulnificus infection. In this report, we profile the D56-mediated molecular changes underlying this resistance in tilapia. A comparative transcriptome analysis was performed on V. vulnificus-infected wild-type and D56-transgenic tilapia using Illumina's sequencing-by-synthesis approach. Gene enrichment analysis on differentially expressed unigenes was performed, and the expression patterns were validated by real-time PCR. RESULTS: Comparative transcriptome analysis was performed on RNA-sequence profiles obtained from wild-type and D56-transgenic tilapia at 0, 6 and 24 h post-infection with V. vulnificaus. GO and KEGG gene enrichment analyses showed that D56 regulates several pathways and genes, including fatty acid (FA) metabolism associated, and inflammatory and immune response. Expression of selected FA metabolism-associated, inflammatory and immune responsive genes was validated by qPCR. The inflammatory and immune responsive genes that are modulated by FA-associated D56 likely contribute to the enhanced resistance against V. vulnificus infection in Tilapia. CONCLUSIONS: Transcriptome profiling and filtering for two-fold change variation showed that 3795 genes were upregulated and 1839 genes were downregulated in D56-transgenic tilapia. These genes were grouped into pathways, such as FA metabolism, FA elongation, FA biosynthesis, biosynthesis of unsaturated FA, FA degradation, inflammation, immune response, and chemokines. FA-associated genes and immune-related genes were modulated by D56 at 6 h and 24 h post infection with V. vulnificus. The expression patterns of FA-related genes, inflammatory genes, antimicrobial peptide genes and immune responsive genes at 0, 3, 6, 12, 24 and 48 h post-infection suggests these genes are involved in the enhanced resistance of D56 transgenic tilapia to V. vulnificus.

A systematic review and meta-analysis on the clinical implications of probability discounting among individuals with Internet gaming disorder.

The significance of probability discounting (PD) among individuals with Internet gaming disorder (IGD) remains unclear. Following the PRISMA guidelines, we systematically searched the PubMed, Embase, and ScienceDirect databases for English articles on Internet addiction that included comparison between individuals with and without IGD as well as probabilistic discounting task as the main outcome from January 1970 to July 2020 using the appropriate keyword strings. The primary outcome was the overall difference in rate of PD, while the secondary outcomes included the difference in PD with magnitude of probabilistic reward and response time of the PD task. Effect size (ES) was calculated through dividing the group means (e.g., h value or AUC) by the pooled standard deviations of the two groups. A total of five studies with 300 participants (i.e., IGD group, n = 150, mean age = 20.27 ± 2.68; healthy controls, n = 150, mean age = 20.70 ± 2.81) were analyzed. The IGD group was more willing to take risks in probabilistic gains but performances on probabilistic losses were similar between the two groups. The IGD group also exhibited a shorter response time (Hedge's g = - 0.51; 95%CI = - 0.87 to - 0.15). Meta-regression demonstrated a positive correlation between maximum reward magnitude and PD rate (p < 0.04). However, significant publication bias was noted among the included studies (Egger's test, p < 0.01). In conclusion, individuals with IGD seemed more impulsive in making risky decisions, especially when the potential gains were expected. Our findings not only supported the use of PD for assessing individuals with IGD but may also provide new insights into appropriate interventions.

The relationship between delay discounting and Internet addiction: A systematic review and meta-analysis.

AIMS: To estimate the difference in delay discounting (DD) between subjects with Internet addiction (IA) and those without as well as to identify significant variables involved in DD. METHODS: Using the keywords related to IA (e.g., "excessive Internet use", "Internet dependence") AND "delayed reward discounting" OR "delay discounting" OR "temporal discounting" OR "delayed gratification" OR time discounting OR intertemporal choice OR impulsive choice, the PubMed, Embase, and PsycINFO databases were searched from inception to June 2020 for English articles with comparison between subjects with IA and those without. Effect sizes were calculated by group means from the k value or area under the curve (AUC). The random-effects models were used. RESULTS: Fourteen studies in total were eligible for the current meta-analysis that involved 696 subjects with IA (mean age = 22.71) and 2,394 subjects without (mean age = 21.91). Subjects with IA had a steeper DD rate (g = 1.10, 95% CI: 0.57-1.64; p ≤ 0.01) compared with that in those without. Regarding DD data, the difference between k value and AUC was significant (p < 0.01; AUC > k). Additionally, the estimation of DD by the paper-and-pencil task was larger than that by the computerized task (p < 0.01). Significant difference in the DD rate was also noted between subjects with Internet gaming disorder (IGD) and those with unspecified IA (p = 0.00; IGD > IA). The percentage of men and task variables were significantly associated with the DD rate (all p < 0.01), suggesting impaired DD in subjects with IA. CONCLUSIONS: Our results suggested the feasibility of utilizing the DD rate as a therapeutic index for cognitive control in IA. Nevertheless, judicious use is recommended taking into consideration the significant difference between k value and AUC.