Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

Exposure to psychotropic drugs and breast cancer risk in patients with bipolar disorder and major depressive disorder: a nested case-control study.

Breast cancer is one of the most prevalent and serious types of cancer globally. Previous literature has shown that women with mental illness may have an increased risk of breast cancer, however whether this risk is associated with the use of psychotropic drugs has yet to be elucidated. This study aimed to assess such risk among women with major depressive disorder (MDD) and bipolar disorder (BD). A nested case-control study design was used with data obtained from the Taiwan National Health Insurance Research Database. Logistic regression analysis with adjustments for demographic characteristics, medical and mental comorbidities, and all-cause clinical visits was performed to estimate the risk of breast cancer according to the cumulative defined daily dose (cDDD) of psychotropic drugs. The study included 1564 women with MDD or BD who had breast cancer, and 15,540 women with MDD or BD who did not have breast cancer. After adjusting for important confounders, the long-term use of valproic acid (odds ratio, 95% confidence interval: 0.58, 0.39-0.56, cDDD ≥ 365), citalopram (0.58, 0.37-0.91, cDDD 180-365), and sertraline (0.77, 0.61-0.91, cDDD ≥ 365) was associated with a lower risk of breast cancer compared to a cDDD < 30. The short-term use of fluvoxamine (0.82, 0.69-0.96, cDDD 30-180), olanzapine (0.54, 0.33-0.89, cDDD 30-179), risperidone (0.7, 0.51-0.98, cDDD 30-179), and chlorpromazine (0.48, 0.25-0.90, cDDD 30-179) was associated with a lower risk of breast cancer. We found no evidence of an increased risk of breast cancer in patients with MDD or BD receiving psychotropic drugs.

Comparing the performance of ChatGPT GPT-4, Bard, and Llama-2 in the Taiwan Psychiatric Licensing Examination and in differential diagnosis with multi-center psychiatrists.

AIM: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well-studied. METHOD: In the first step, we compared the performance of ChatGPT GPT-4, Bard, and Llama-2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis. RESULT: Only GPT-4 passed the 2022 Taiwan Psychiatric Licensing Examination (scoring 69 and ≥ 60 being considered a passing grade), while Bard scored 36 and Llama-2 scored 25. GPT-4 outperformed Bard and Llama-2, especially in the areas of 'Pathophysiology & Epidemiology' (χ2 = 22.4, P < 0.001) and 'Psychopharmacology & Other therapies' (χ2 = 15.8, P < 0.001). In the differential diagnosis, the mean score of the 24 experienced psychiatrists (mean 6.1, standard deviation 1.9) was higher than that of GPT-4 (5), Bard (3), and Llama-2 (1). CONCLUSION: Compared to Bard and Llama-2, GPT-4 demonstrated superior abilities in identifying psychiatric symptoms and making clinical judgments. Besides, GPT-4's ability for differential diagnosis closely approached that of the experienced psychiatrists. GPT-4 revealed a promising potential as a valuable tool in psychiatric practice among the three LLMs.

Risk of major mental disorders in the offspring of parents with migraine.

BACKGROUND: Migraine has been associated with mental disorders, however whether parental migraine is associated with an increased risk of major mental disorders (MMDs) in offspring has not been investigated. We aimed to examine the risk of the development of MMDs in the offspring of parents with migraine compared with those of parents without migraine. METHODS: This study used data derived from the Taiwan National Health Insurance Research Database. Offspring of parents with migraine and a control group consisting of offspring of parents without migraine matched for demographic and parental mental disorders were included. Cox regression was used to estimate the risk of MMDs, including schizophrenia, depressive disorder, bipolar disorder, autistic spectrum disorder (ASD), and attention deficit/hyperactivity disorder (ADHD). Sub-analyses stratified by the fathers and mothers were further performed to separately clarify the risks of MMDs among the offspring. RESULTS: We included 22,747 offspring of parents with migraine and 227,470 offspring of parents without migraine as the controls. Parental migraine was significantly associated with an increased risk of ADHD (reported as hazard ratios with 95% confidence intervals: 1.37, 1.25-1.50), bipolar disorder (1.35, 1.06-1.71), and depressive disorder (1.33, 1.21-1.47) compared to the offspring of parents without migraine. Importantly, sub-analyses showed that only maternal migraine was significantly associated with these risks. CONCLUSIONS: Due to the heavy burden of MMDs, healthcare workers should be aware of the risk of MMDs in the offspring of parents with migraine, particular in mothers.

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.

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.

Association between parental bipolar disorder and increased risk of exposure to prescription opioids for their offspring.

PURPOSE: Individuals with bipolar disorder (BD) may have an increased risk of exposure to prescription opioids. However, it is still unknown whether such risk also occurs in their offspring. This study aimed to investigate the risk of exposure to prescription opioid use and related medical conditions in the offspring of parents with BD. METHODS: This study used the Taiwan National Health Research Database and included offspring who had any parent with a diagnosis of BD. The matched-control cohort was randomly identified from the offspring of parents without any major psychiatric disorders (MPD). We identified data pertaining to opioid prescription and related medical conditions, namely pain disorder, malignancy, autoimmune disease, and arthropathy. The Poisson regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: In total, 11,935 offspring of parents with BD and 119,350 offspring of parents without any MPD were included. After controlling for demographics and mental disorders, offspring of parents with BD demonstrated higher rates of prescription opioid use than those of parents without MPD, especially the intravenous/intramuscular form of opioids and prescription in hospital settings. In addition, offspring of parents with BD had a higher odds of pain disorders than those of parents without MPD. CONCLUSION: Our study identifies a higher odd for developing pain disorders and exposure to prescription opioids among children of parents with BD.

Placebo effects on all-cause mortality of patients with COVID-19 in randomized controlled trials of interleukin 6 antagonists: A systematic review and network meta-analysis.

AIM: Many randomized controlled trials (RCTs) have investigated the use of interleukin 6 antagonists for the treatment of coronavirus disease 2019 (COVID-19), yielding inconsistent results. This network meta-analysis (NMA) aimed to identify the source of these inconsistent results by reassessing whether participants treated with standard of care (SoC) plus placebo have different all-cause mortality from those treated with SoC alone and to reevaluate the efficacy of interleukin 6 antagonists in the treatment of COVID-19. METHODS: We conducted a systematic search for relevant RCTs from the inception of electronic databases through 1 September 2022. The primary outcome was all-cause mortality. The secondary outcomes were the incidences of major medical events, secondary infections, all-cause discontinuation, and serious adverse events. RESULTS: The results of NMA of 33 RCTs showed that patients with COVID-19 treated with SoC plus placebo had lower odds of all-cause mortality than those who received SoC alone (OR, 0.75 [95% confidence interval, 0.58-0.97]). This finding remained consistent after excluding studies with no incident deaths. In addition, when we consider the impact of the widely promoted COVID-19 vaccination and newly developed antiviral treatment strategy, the results from the analysis of the RCT published in 2021 and 2022 remained similar. CONCLUSION: These findings suggest the potential influence of placebo effects on the treatment outcomes of COVID-19 in RCTs. When evaluating the efficacy of treatment strategies for COVID-19, it is crucial to consider the use of placebo in the design of clinical trials.

Efficacy of online training at the International Mental Health Training Center Taiwan (IMHTCT): Pre and during the COVID-19 pandemic.

STUDY OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has resulted in major disruption to regular learning and training for medical staff. The aim of this study was to compare the learning efficacy between on-site training before the COVID-19 pandemic and online training during the pandemic for nurses, psychologists, social workers, and occupational therapists from Southeast Asia. METHOD: The current study derived data from the International Mental Health Training Center Taiwan (IMHTCT) from 2018 to 2020. IMHTCT Trainees Learning Effect Questionnaire (ITLEQ) scores of the medical staff and demographic variables were collected. Reliability and validity of the ITLEQ were estimated. The independent t-test was used to compare differences in ITLEQ scores between the pre-training and post-training stages among the trainees. In addition, generalized estimating equations were used to estimate the predictive effect of online training on changes in ITLEQ scores over time. FINDINGS: A total of 190 trainees were enrolled, including 92 social workers, 16 occupation therapists, 24 psychologists, and 58 nurses. The reliability and validity were satisfactory. The efficacy of the training programs at IMHTCT was significant for all of the healthcare workers. Furthermore, better training efficacy was found in the social workers and occupational therapists who received online training compared to those who received on-site training. The potential efficacy of online training was found in the nurses. CONCLUSION: Our results demonstrate the importance of online training for mental healthcare workers during the COVID-19 pandemic. Online training may be implemented into regular training courses in the future.

Risks of major mental disorders after parental death in children, adolescents, and young adults and the role of premorbid mental comorbidities: a population-based cohort study.

Previous studies have shown an association between early parental death and the risk of subsequent major mental disorders (MMDs) among the bereaved children and adolescents; however, it is unclear whether this risk exists in young adults and in individuals with premorbid mental comorbidities. We aimed to explore differences between children, adolescents, and young adults in the risk of MMDs after parental death. We analyzed data from the Taiwan National Health Research Database. The index cohort was offspring (divided into four groups: aged < 6, 6-11, 12-17, and 18-29 years) whose parents had died. The control cohort was demographically matched offspring whose parents were still alive. Cox regression with adjustments for demographics was used to estimate the risk of subsequent MMDs between the index and control cohorts, including schizophrenia, bipolar disorder, and depressive disorder. We included 202,837 cases and 2,028,370 matched controls. As with the bereaved children and adolescents, the bereaved young adults had a significantly higher risk of schizophrenia (hazard ratio with 95% confidence interval: 5.63; 5.01-6.33), bipolar disorder (3.37; 2.96-3.84), and depressive disorder (2.78; 2.68-2.90) than the control cohort. The risk of MMDs was similar for maternal death and paternal death. Among premorbid mental comorbidities, bereaved individuals with premorbid substance use disorder were associated with the highest risk of schizophrenia (10.43; 8.57-12.71), bipolar disorder (12.93; 10.59-15.79), and depressive disorder (10.97; 10.22-11.78). Healthcare workers should be aware that young adults and individuals with premorbid mental comorbidities are at a higher risk of subsequent MMDs than those without premorbid mental comorbidities after parental death.

Risk of pain disorders in offspring of parents with substance use disorders.

AIMS: Individuals with substance use disorders (SUD) have higher risk of developing pain disorders. This study aimed to investigate the risk of major psychiatric disorders (MPD), SUD, and pain disorders among their offspring. METHODS: This study used data from the Taiwan National Health Research Database. The case cohort included participants who had a parent diagnosed with SUD. The matched control cohort was offspring of parents without any SUD or major psychiatric disorder (MPD). Poisson regression was applied to estimate the risk of MPD, SUD, and pain disorder between case and control cohorts. RESULTS: We recruited 13,840 cases and 138,400 matched controls. After adjusting for demographic characteristics and family history of psychiatric disorder, the offspring of parents with SUD had higher risk for bipolar disorder (reported as risk ratio with 95% confidence interval: 2.48, 1.79-3.43), depressive disorder (2.22, 1.94-2.52), SUD (2.53, 2.18-2.92), and alcohol use disorder (1.43, 1.16-1.76) than controls. With adjustments of demographic characteristics, individual MPD, and family history of psychiatric disorder, they also presented higher risk than controls for several pain disorders, including migraine (1.43, 1.15-1.78), fibromyalgia (1.21, 1.03-1.42), dorsopathies (1.20, 1.06-1.37), dysmenorrhea (1.16, 1.04-1.29), irritable bowel syndrome (1.26, 1.11-1.43), and dyspepsia (1.14, 1.02-1.27). CONCLUSIONS: Clinicians should be aware of the influence of parental SUD on the elevated risk for MPD, SUD, and pain disorders in their offspring.

Multiple comparison of different noninvasive brain stimulation and pharmacologic interventions in patients with methamphetamine use disorders: A network meta-analysis of randomized controlled trials.

AIM: In recent decades, the prevalence of amphetamine and methamphetamine use disorders has at least doubled in some regions/countries, with accompanying high risks of drug overdose-associated mortality. Noninvasive brain stimulation (NIBS) methods may be effective treatments. However, the comparative efficacy of the NIBS protocol for amphetamine/methamphetamine use disorder (AUD/MUD) remains unknown to date. The aim of this network meta-analysis (NMA) was to compare the efficacy and acceptability of various NIBS methods/protocols for AUD/MUD management. METHODS: A frequentist model-based NMA was conducted. We included randomized controlled trials (RCTs) that investigated the efficacy of NIBS and guideline-recommended pharmacologic treatments to reduce craving severity in patients with either AUD or MUD. RESULTS: Twenty-two RCTs including 1888 participants met the eligibility criteria. Compared with the sham/placebo group (study = 19, subjects = 891), a combination of intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS over the left ventromedial prefrontal cortex (study = 1, subjects = 19) was associated with the largest decreases in craving severity [standardized mean difference (SMD) = -1.50; 95% confidence intervals (95%CIs) = -2.70 to -0.31]. High-frequency repetitive transcranial magnetic stimulation over the left DLPFC was associated with the largest improvements in depression and quality of sleep (study = 3, subjects = 86) (SMD = -2.48; 95%CIs = -3.25 to -1.71 and SMD = -2.43; 95%CIs = -3.38 to -1.48, respectively). The drop-out rate of most investigated treatments did not significantly differ between groups. CONCLUSION: The combined TBS protocol over the prefrontal cortex was associated with the greatest improvement in craving severity. Since few studies were available for inclusion, additional large-scale randomized controlled trials are warranted.

Efficacy of music therapy and predictors of sleep disturbance among patients with chronic schizophrenia: A prospective study.

STUDY OBJECTIVES: Patients with schizophrenia often suffer from sleep disturbance. Music therapy, as a non-invasive intervention, may have benefit on sleep problem in such population. Our study aimed to investigate the efficacy of music therapy on sleep disturbance among patients with schizophrenia. METHOD: This prospective study recruited participants with schizophrenia along with sleep disturbances in the chronic wards. Patients in the control group received standard care, and those in the intervention group received additional music therapy before sleeping at night for four weeks. The Pittsburgh Sleep Quality Index (PSQI) was used to measure the severity of sleep disturbance. The generalized estimating equation (GEE) was used to analyze measure the difference of change in PSQI scores between both groups at the baseline and four weeks later. It was also applied to find the predictors of treatment efficacy within intervention group. FINDINGS: A total of 66 (31 in control group and 35 in intervention group) participants were recruited. After adjusting with the demographic variables, the change of PSQI among intervention group was significantly more than the change among control group (Group × time; Estimate = -7.05, p < 0.001), indicating the efficacy of music therapy. In addition, irreligious patients and those with chronic medical disease predicted better efficacy. Whereas, elderly patients had compromising efficacy of music therapy. CONCLUSION: Music therapy demonstrated its merit on sleep disturbance among patients with schizophrenia. Whereas, healthcare workers should consider the variability of severity in schizophrenia during clinical practice.

Cognitive effects and acceptability of non-invasive brain stimulation on Alzheimer's disease and mild cognitive impairment: a component network meta-analysis.

OBJECTIVES: To compare cognitive effects and acceptability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) in patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI), and to determine whether cognitive training (CT) during rTMS or tDCS provides additional benefits. METHODS: Electronic search of PubMed, Medline, Embase, the Cochrane Library and PsycINFO up to 5 March 2020. We enrolled double-blind, randomised controlled trials (RCTs). The primary outcomes were acceptability and pre-post treatment changes in general cognition measured by Mini-Mental State Examination, and the secondary outcomes were memory function, verbal fluency, working memory and executive function. Durability of cognitive benefits (1, 2 and ≥3 months) after brain stimulation was examined. RESULTS: We included 27 RCTs (n=1070), and the treatment components included high-frequency rTMS (HFrTMS) and low-frequency rTMS, anodal tDCS (atDCS) and cathodal tDCS (ctDCS), CT, sham CT and sham brain stimulation. Risk of bias of evidence in each domain was low (range: 0%-11.1%). HFrTMS (1.08, 9, 0.35-1.80) and atDCS (0.56, 0.03-1.09) had short-term positive effects on general cognition. CT might be associated with negative effects on general cognition (-0.79, -2.06 to 0.48) during rTMS or tDCS. At 1-month follow-up, HFrTMS (1.65, 0.77-2.54) and ctDCS (2.57, 0.20-4.95) exhibited larger therapeutic responses. Separate analysis of populations with pure AD and MCI revealed positive effects only in individuals with AD. rTMS and tDCS were well tolerated. CONCLUSIONS: HFrTMS is more effective than atDCS for improving global cognition, and patients with AD may have better responses to rTMS and tDCS than MCI.

Therapeutic benefits of pharmacologic and nonpharmacologic treatments for depressive symptoms after traumatic brain injury: a systematic review and network meta-analysis.

Background: Depression is a common morbidity after traumatic brain injury. This network meta-analysis investigated the efficacy and tolerability of pharmacologic and nonpharmacologic interventions for depression after traumatic brain injury. Methods: We extracted randomized controlled trials examining pharmacologic or nonpharmacologic interventions with placebo- or active-controlled designs from PubMed, the Cochrane Library and ScienceDirect, from inception to October 30, 2018. We based study selection and extraction of a predefined list of variables on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines, and conducted meta-analysis procedures using random effects modelling. Primary outcomes were changes in depressive symptom severity after pharmacologic or nonpharmacologic treatment; the secondary outcome was tolerability, reflected in overall patient dropout rates. Results: Our analysis of 27 randomized controlled trials (10 pharmacologic, total n = 483, mean age = 37.9 yr; 17 nonpharmacologic, total n = 1083, mean age = 38.0 yr) showed that methylphenidate had significantly superior efficacy compared to placebo or control (standardized mean difference -0.91, 95% confidence interval [CI] -1.49 to -0.33). Sertraline was associated with significantly lower tolerability (i.e., a higher dropout rate) compared to placebo or control (odds ratio 2.65, 95% CI 1.27 to 5.54). No nonpharmacologic treatment was more effective than the others, and we found no significant differences in tolerability (i.e., dropout rates) among the nonpharmacologic treatments. Limitations: Heterogeneity in participant characteristics (e.g., comorbidities), study designs (e.g., trial duration) and psychopathology assessment tools, as well as small trial numbers for some treatment arms, could have been confounders. Conclusion: The present network meta-analysis suggests that methylphenidate might be the best pharmacologic intervention for depressive symptoms related to traumatic brain injury. None of the nonpharmacologic interventions was associated with better improvement in depressive symptoms than the others or than control conditions. None of the pharmacologic or nonpharmacologic treatments had inferior tolerability compared to placebo or controls except for sertraline, which had significantly lower tolerability than placebo.

The association between melatonin and episodic migraine: A pilot network meta-analysis of randomized controlled trials to compare the prophylactic effects with exogenous melatonin supplementation and pharmacotherapy.

Although exogenous melatonin supplementation has been suggested to be effective for episodic migraine prophylaxis, there is no conclusive evidence comparing the efficacy of exogenous melatonin supplementation to the other FDA-approved pharmacotherapy for episodic migraine prophylaxis. The aim of the current network meta-analysis (NMA) was to compare the efficacy of exogenous melatonin supplementation in patients with episodic migraine. The randomized placebo-controlled trials or randomized controlled trials (RCTs) incorporating a placebo in the study designs were included in our analyses. All of the NMA procedures were conducted under the frequentist model. The primary outcome was changes in frequency of migraine days and response rate after migraine prophylaxis with melatonin supplementation or pharmacological interventions. We included 25 RCTs in total with 4499 patients (mean age = 36.0 years, mean female proportion = 78.9%). The NMA demonstrated that migraine prophylaxis with oral melatonin 3 mg/d (immediate-release) at bedtime was associated with the greatest improvement in migraine frequency [mean difference = -1.71 days, 95% confidence interval (CI): -3.27 to -0.14 days compared to placebo] and the second highest response rate (odds ratio = 4.19, 95% CI = 1.46 to 12.00 compared to placebo). Furthermore, oral melatonin 3 mg (immediate-release) at bedtime was the most preferred pharmacological intervention among all of the investigated interventions when improvements in migraine frequency, response rate, dropout rate, and rates of any adverse events were taken into account. This pilot NMA suggests the potential prophylactic role of exogenous melatonin supplementation in patients with episodic migraine.

COVID-19-Related Information Sources and the Relationship With Confidence in People Coping with COVID-19: Facebook Survey Study in Taiwan.

BACKGROUND: People obtain information on the coronavirus disease (COVID-19) from the internet and other sources. Understanding the factors related to such information sources aids health professionals in educating individuals. OBJECTIVE: This study used data collected from the online survey study on COVID-19 in Taiwan to examine what major COVID-19 information sources are available and which sources are significantly related to the self-confidence of people in coping with COVID-19 in Taiwan. METHODS: A total of 1904 participants (1270 non-health-care workers and 634 health care workers) were recruited from the Facebook advertisement. Their major sources of information about COVID-19, the relationships between the sources and demographic factors, and the relationships between the sources and the self-confidence in coping with COVID-19 were surveyed. RESULTS: Most Taiwanese people relied on the internet for COVID-19 information. Many respondents also used a variety of sources of information on COVID-19; such variety was associated with sex, age, and the level of worry toward COVID-19, as well as if one was a health care worker. For health care workers, the use of formal lessons as an information source was significantly associated with better self-confidence in coping with COVID-19. The significant association between receiving information from more sources and greater self-confidence was found only in health care workers but not in non-health-care workers. CONCLUSIONS: Medical professionals should consider subgroups of the population when establishing various means to deliver information on COVID-19.

Maternal breastfeeding and autism spectrum disorder in children: A systematic review and meta-analysis.

OBJECTIVES: Autism spectrum disorder (ASD) refers to a group of conditions variably affecting communicative and social interactive abilities presenting alongside behaviors with various restricted and repetitive patterns. In addition to genetic factors that influence the onset of the symptoms, there is growing interest in the potential involvement of non-genetic environmental factors. Some aspects of breastfeeding practices, including rates, timing, or optimality, have been put forward as environmental risk factors for autism. However, previous studies showed a controversial relationship between ASD and breastfeeding. METHODS: A meta-analysis on the association between maternal breastfeeding and ASD in children was conducted. We also explored potential moderating factors which might influence this association. Articles reporting the association between breastfeeding and a diagnosis of ASD were included. RESULTS: Seven articles were included in the meta-analysis. Cumulatively, children with ASD (n = 1463), either in the form of clinical diagnosis or self-report, were significantly less likely to have been breastfed than children without ASD (n = 1180) (OR = 0.61, 95% CI = 0.45-0.83, P = 0.002). Subgroup analyses revealed that results remained significant for children who were breastfed with additional supplementation. DISCUSSION: This meta-analysis provides evidence that breastfeeding (exclusively or including additional supplements) may protect against ASD. Prospective longitudinal research is required to disentangle the complex relationships and to explore potential pathophysiological mechanisms.

Serum folate levels in bipolar disorder: a systematic review and meta-analysis.

BACKGROUND: Bipolar disorder (BD) is a major psychiatric illness, however its physiopathology is unclear. The role of folate in the physiopathology of BD is controversial. We conducted this systematic review and meta-analysis to investigate the effect of folate in BD patients. METHODS: We performed a thorough literature study of the PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, and ClinicalTrials.gov databases until December 21st, 2018. Random effects meta-analysis was conducted. RESULTS: Six articles involving 481 patients with BD and 760 controls were included. The meta-analysis results suggested that serum folate levels in the patients with BD were significantly lower than those in the controls (Hedges' g = - 0.211, 95% confidence interval = - 0.391 to - 0.031, p = 0.021). CONCLUSION: The current meta-analysis show it might be association between lower serum folate levels and patient with BD. However, we could not distinguish the potentially confounding effects of mood states on the folate levels. Further prospective studies including subjects with different mood states and possible physiopathology are warranted to investigate the association between folate deficiency and the etiology of BD.

Maternal breastfeeding and attention-deficit/hyperactivity disorder in children: a meta-analysis.

Previous studies have suggested environmental factors may contribute to the risk of attention-deficit/hyperactivity disorder (ADHD). The current meta-analysis examined (1) the difference in the duration of maternal breastfeeding between children with and without ADHD, and (2) the association between maternal breastfeeding and ADHD in children. The data of individual studies were synthesized with a random-effects model. Eleven articles were included in this meta-analysis. Children with ADHD had significantly less breastfeeding duration than controls (Hedges' g = - 0.36, 95% confidence intervals (CIs) = - 0.61 to - 0.11, p = 0.005; difference in means: - 2.44 months, 95% CIs = - 3.17 to - 1.71, p < 0.001). In addition, the rates of non-exclusive breastfeeding in children with ADHD is significantly higher in "under 3 months" (odds ratio (OR) = 1.90, 95% CIs = 1.45 to 2.48, p < 0.001) but lower in "6 to 12 months" (OR = 0.69, 95% CIs = 0.49 to 0.98, p = 0.039) and "over 12 months" (OR = 0.58, 95% CIs = 0.35 to 0.97, p = 0.038) than controls. Children with ADHD received significantly higher rate of exclusive breastfeeding duration "under 3 months" (OR = 1.51, 95% CIs = 1.20 to 1.89, p < 0.001) but lower in "over 3 months" (OR = 0.52, 95% CIs = 0.29 to 0.95, p = 0.033) than controls. Furthermore, an association was found between non-breastfeeding and ADHD children (adjusted OR = 3.71, 95% CI = 1.94 to 7.11, p < 0.001). Our results suggest maternal breastfeeding is associated with a lower risk of ADHD in children. Future longitudinal research is required to confirm/refute these findings and to explore possible mechanisms underlying this association.