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Major depressive disorder (MDD) is a tremendous global disease burden and the leading cause of disability worldwide. Unfortunately, individuals diagnosed with MDD typically experience a delayed response to traditional antidepressants and many do not adequately respond to pharmacotherapy, even after multiple trials. The critical need for novel antidepressant treatments has led to a recent resurgence in the clinical application of psychedelics, and intravenous ketamine, which has been investigated as a rapid-acting treatment for treatment resistant depression (TRD) as well acute suicidal ideation and behavior. However, variations in the type and quality of experimental design as well as a range of treatment outcomes in clinical trials of ketamine make interpretation of this large body of literature challenging.
Objectives
This umbrella review aims to advance our understanding of the effectiveness of intravenous ketamine as a pharmacotherapy for TRD by providing a systematic, quantitative, large-scale synthesis of the empirical literature.
Methods
We performed a comprehensive PubMed search for peer-reviewed meta-analyses of primary studies of intravenous ketamine used in the treatment of TRD. Meta-analysis and primary studies were then screened by two independent coding teams according to pre-established inclusion criteria as well as PRISMA and METRICS guidelines. We then employed metaumbrella, a statistical package developed in R, to perform effect size calculations and conversions as well as statistical tests.
Results
In a large-scale analysis of 1,182 participants across 51 primary studies, repeated-dose administration of intravenous ketamine demonstrated statistically significant effects (p<0.05) compared to placebo-controlled as well as other experimental conditions in patients with TRD, as measured by standardized clinician-administered and self-report depression symptom severity scales.
Conclusions
This study provides large-scale, quantitative support for the effectiveness of intravenous, repeated-dose ketamine as a therapy for TRD and a report of the relative effectiveness of several treatment parameters across a large and rapidly growing literature. Future investigations should use similar analytic tools to examine evidence-stratified conditions and the comparative effectiveness of other routes of administration and treatment schedules as well as the moderating influence of other clinical and demographic variables on the effectiveness of ketamine on TRD and suicidal ideation and behavior.
Panic disorder (PD) and agoraphobia (AG) are highly comorbid anxiety disorders with an increasing prevalence that have a significant clinical and public health impact but are not adequately recognized and treated. Although the current functional neuroimaging literature has documented a range of neural abnormalities in these disorders, primary studies are often not sufficiently powered and their findings have been inconsistent.
Objectives
This meta-analysis aims to advance our understanding of the neural underpinnings of PD and AG by identifying the most robust patterns of differential neural activation that differentiate individuals diagnosed with one of or both these disorders from age-matched healthy controls.
Methods
We conducted a comprehensive literature search in the PubMed database for all peer-reviewed, whole-brain, task-based functional magnetic resonance imaging (fMRI) activation studies that compared adults diagnosed with PD and/or AG with age-matched healthy controls. Each of these articles was screened by two independent coding teams using formal inclusion criteria and according to current PRISMA guidelines. We then performed a voxelwise, whole-brain, meta-analytic comparison of PD/AG participants with age-matched healthy controls using multilevel kernel density analysis (MKDA) with ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
With data from 34 primary studies and a substantial sample size (N=2138), PD/AG participants, relative to age-matched healthy controls, exhibited a reliable pattern of statistically significant, (p<.05-0.0001; FWE-corrected) abnormal neural activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
In this meta-analysis we found robust patterns of differential neural activation in participants diagnosed with PD/AG relative to age-matched healthy controls. These findings advance our understanding of the neural underpinnings of PD and AG and inform the development of brain-based clinical interventions such as non-invasive brain stimulation (NIBS) and treatment prediction and matching algorithms. Future studies should also investigate the neural similarities and differences between PD and AG to increase our understanding of possible differences in their etiology, diagnosis, and treatment.
There has been rapidly growing interest in understanding the pharmaceutical and clinical properties of psychedelic and dissociative drugs, with a particular focus on ketamine. This compound, long known for its anesthetic and dissociative properties, has garnered attention due to its potential to rapidly alleviate symptoms of depression, especially in individuals with treatment-resistant depression (TRD) or acute suicidal ideation or behavior. However, while ketamine’s psychopharmacological effects are increasingly well-documented, the specific patterns of its neural impact remain a subject of exploration and basic questions remain about its effects on functional activation in both clinical and healthy populations.
Objectives
This meta-analysis seeks to contribute to the evolving landscape of neuroscience research on dissociative drugs such as ketamine by comprehensively examining the effects of acute ketamine administration on neural activation, as measured by functional magnetic resonance imaging (fMRI), in healthy participants.
Methods
We conducted a meta-analysis of existing fMRI activation studies of ketamine using multilevel kernel density analysis (MKDA). Following a comprehensive PubMed search, we quantitatively synthesized all published primary fMRI whole-brain activation studies of the effects of ketamine in healthy subjects with no overlapping samples (N=18). This approach also incorporated ensemble thresholding (α=0.05-0.0001) to minimize cluster-size detection bias and Monte Carlo simulations to correct for multiple comparisons.
Results
Our meta-analysis revealed statistically significant (p<0.05-0.0001; FWE-corrected) alterations in neural activation in multiple cortical and subcortical regions following the administration of ketamine to healthy participants (N=306).
Conclusions
These results offer valuable insights into the functional neuroanatomical effects caused by acute ketamine administration. These findings may also inform development of therapeutic applications of ketamine for various psychiatric and neurological conditions. Future studies should investigate the neural effects of ketamine administration, including both short-term and long-term effects, in clinical populations and their relation to clinical and functional improvements.
Bipolar I disorder (BD-I) is a chronic and recurrent mood disorder characterized by alternating episodes of depression and mania; it is also associated with substantial morbidity and mortality and with clinically significant functional impairments. While previous studies have used functional magnetic resonance imaging (fMRI) to examine neural abnormalities associated with BD-I, they have yielded mixed findings, perhaps due to differences in sampling and experimental design, including highly variable mood states at the time of scan.
Objectives
The purpose of this study is to advance our understanding of the neural basis of BD-I and mania, as measured by fMRI activation studies, and to inform the development of more effective brain-based diagnostic systems and clinical treatments.
Methods
We conducted a large-scale meta-analysis of whole-brain fMRI activation studies that compared participants with BD-I, assessed during a manic episode, to age-matched healthy controls. Following PRISMA guidelines, we conducted a comprehensive PubMed literature search using two independent coding teams to evaluate primary studies according to pre-established inclusion criteria. We then used multilevel kernel density analysis (MKDA), a well-established, voxel-wise, whole-brain, meta-analytic approach, to quantitatively synthesize all qualifying primary fMRI activation studies of mania. We used ensemble thresholding (p<0.05-0.0001) to minimize cluster size detection bias, and 10,000 Monte Carlo simulations to correct for multiple comparisons.
Results
We found that participants with BD-I (N=2,042), during an active episode of mania and relative to age-matched healthy controls (N=1,764), exhibit a pattern of significantly (p<0.05-0.0001; FWE-corrected) different activation in multiple brain regions of the cerebral cortex and basal ganglia across a variety of experimental tasks.
Conclusions
This study supports the formulation of a robust neural basis for BD-I during manic episodes and advances our understanding of the pattern of abnormal activation in this disorder. These results may inform the development of novel brain-based clinical tools for bipolar disorder such as diagnostic biomarkers, non-invasive brain stimulation, and treatment-matching protocols. Future studies should compare the neural signatures of BD-I to other related disorders to facilitate the development of protocols for differential diagnosis and improve treatment outcomes in patients with BD-I.
Majority of international guidelines for bipolar disorders are based on evidences from clinical trials. In contrast, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea.
Objectives
In this study, preferred medication strategies for acute mania over six consecutively published KMAP-BP (2002, 2006, 2010, 2014, 2018, and 2022) were investigated.
Methods
A written survey using a nine-point scale was asked to Korean experts about the appropriateness of various treatment strategies and treatment agents. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line.
Results
The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) in every edition. Preference for combined treatment for euphoric mania increased, peaked in KMAP-BP 2010, and declined slightly. Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. Among MSs, lithium and valproate are almost equally preferred except in the mixed subtype where valproate is the most recommended MS. The preference of valproate showed reverse U-shaped curve. This preference change of valproate may indicate the concern about teratotoxicity in women. Quetiapine, aripiprazole, and olanzapine were the preferred AAP for acute mania since 2014. This change might depend on the recent evidences and safety profile. In cases of unsatisfactory response to initial medications, switching or adding another first-line agent was recommended. The most notable changes over time included the increasing preference for AAPs.
Conclusions
The Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute mania. There have been evident preference changes: increased for AAP and decreased for carbamazepine.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric condition that frequently originates in early development and is associated with a variety of functional impairments. Despite a large functional neuroimaging literature on ADHD, our understanding of the neural basis of this disorder remains limited, and existing primary studies on the topic include somewhat divergent results.
Objectives
The present meta-analysis aims to advance our understanding of the neural basis of ADHD by identifying the most statistically robust patterns of abnormal neural activation throughout the whole-brain in individuals diagnosed with ADHD compared to age-matched healthy controls.
Methods
We conducted a meta-analysis of task-based functional magnetic resonance imaging (fMRI) activation studies of ADHD. This included, according to PRISMA guidelines, a comprehensive PubMed search and predetermined inclusion criteria as well as two independent coding teams who evaluated studies and included all task-based, whole-brain, fMRI activation studies that compared participants diagnosed with ADHD to age-matched healthy controls. We then performed multilevel kernel density analysis (MKDA) a well-established, whole-brain, voxelwise approach that quantitatively combines existing primary fMRI studies, with ensemble thresholding (p<0.05-0.0001) and multiple comparisons correction.
Results
Participants diagnosed with ADHD (N=1,550), relative to age-matched healthy controls (N=1,340), exhibited statistically significant (p<0.05-0.0001; FWE-corrected) patterns of abnormal activation in multiple brains of the cerebral cortex and basal ganglia across a variety of cognitive control tasks.
Conclusions
This study advances our understanding of the neural basis of ADHD and may aid in the development of new brain-based clinical interventions as well as diagnostic tools and treatment matching protocols for patients with ADHD. Future studies should also investigate the similarities and differences in neural signatures between ADHD and other highly comorbid psychiatric disorders.
BMI z (BMIz) score based on the Centers for Disease Control and Prevention growth charts is widely used, but it is inaccurate above the 97th percentile. We explored the performance of alternative metrics based on the absolute distance or % distance of a child’s BMI from the median BMI for sex and age. We used longitudinal data from 5628 children who were first examined <12 years to compare the tracking of three BMI metrics: distance from median, % distance from median and % distance from median on a log scale. We also explored the effects of adjusting these metrics for age differences in the distribution of BMI. The intraclass correlation coefficient (ICC) was used to compare tracking of the metrics. Metrics based on % distance (whether on the original or log scale) yielded higher ICCs compared with distance from median. The ICCs of the age-adjusted metrics were higher than that of the unadjusted metrics, particularly among children who were (1) overweight or had obesity, (2) younger and (3) followed for >3 years. The ICCs of the age-adjusted metrics were also higher compared with that of BMIz among children who were overweight or obese. Unlike BMIz, these alternative metrics do not have an upper limit and can be used for assessing BMI in all children, even those with very high BMIs. The age-adjusted % from median (on a log or linear scale) works well for all ages, while unadjusted % from median is better limited to older children or short follow-up periods.
Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.
Introduction: Point of care ultrasound has become an established tool in the initial management of patients with undifferentiated hypotension. Current established protocols (RUSH, ACES, etc) were developed by expert user opinion, rather than objective, prospective data. We wished to use reported disease incidence to develop an informed approach to PoCUS in hypotension using a “4 F’s” approach: Fluid; Form; Function; Filling. Methods: We summarized the incidence of PoCUS findings from an international multicentre RCT, and using a modified Delphi approach incorporating this data we obtained the input of 24 international experts associated with five professional organizations led by the International Federation of Emergency Medicine. The modified Delphi tool was developed to reach an international consensus on how to integrate PoCUS for hypotensive emergency department patients. Results: Rates of abnormal PoCUS findings from 151 patients with undifferentiated hypotension included left ventricular dynamic changes (43%), IVC abnormalities (27%), pericardial effusion (16%), and pleural fluid (8%). Abdominal pathology was rare (fluid 5%, AAA 2%). After two rounds of the survey, using majority consensus, agreement was reached on a SHoC-hypotension protocol comprising: A. Core: 1. Cardiac views (Sub-xiphoid and parasternal windows for pericardial fluid, cardiac form and ventricular function); 2. Lung views for pleural fluid and B-lines for filling status; and 3. IVC views for filling status; B. Supplementary: Additional cardiac views; and C. Additional views (when indicated) including peritoneal fluid, aorta, pelvic for IUP, and proximal leg veins for DVT. Conclusion: An international consensus process based on prospectively collected disease incidence has led to a proposed SHoC-hypotension PoCUS protocol comprising a stepwise clinical-indication based approach of Core, Supplementary and Additional PoCUS views.
Introduction: Point of care ultrasound (PoCUS) provides invaluable information during resuscitation efforts in cardiac arrest by determining presence/absence of cardiac activity and identifying reversible causes such as pericardial tamponade. There is no agreed guideline on how to safely and effectively incorporate PoCUS into the advanced cardiac life support (ACLS) algorithm. We consider that a consensus-based priority checklist using a “4 F’s” approach (Fluid; Form; Function; Filling), would provide a better algorithm during ACLS. Methods: The ultrasound subcommittee of the Australasian College for Emergency Medicine (ACEM) drafted a checklist incorporating PoCUS into the ACLS algorithm. This was further developed using the input of 24 international experts associated with five professional organizations led by the International Federation of Emergency Medicine. A modified Delphi tool was developed to reach an international consensus on how to integrate ultrasound into cardiac arrest algorithms for emergency department patients. Results: Consensus was reached following 3 rounds. The agreed protocol focuses on the timing of PoCUS as well as the specific clinical questions. Core cardiac windows performed during the rhythm check pause in chest compressions are the sub-xiphoid and parasternal cardiac views. Either view should be used to detect pericardial fluid, as well as examining ventricular form (e.g. right heart strain) and function, (e.g. asystole versus organized cardiac activity). Supplementary views include lung views (for absent lung sliding in pneumothorax and for pleural fluid), and IVC views for filling. Additional ultrasound applications are for endotracheal tube confirmation, proximal leg veins for DVT, or for sources of blood loss (AAA, peritoneal/pelvic fluid). Conclusion: The authors hope that this process will lead to a consensus-based SHoC-cardiac arrest guideline on incorporating PoCUS into the ACLS algorithm.
This study aimed to evaluate the efficacy of post-operative voice therapy after phonomicrosurgery for vocal polyp removal.
Methods:
The study retrospectively enrolled 55 consecutive patients who had undergone voice therapy after phonomicrosurgery for vocal polyp removal occurring between June 2010 and June 2011. A historical group of 63 similar patients not receiving voice therapy was used as an external control. We compared voice analysis parameters and Voice Handicap Index scores for the two groups.
Results:
Most objective and subjective voice outcome parameters were significantly improved after surgical treatment. Although the study and control groups showed no significant difference regarding objective parameters (using acoustic and aerodynamic analysis) or the subjective parameters assessed using the grade-roughness-breathiness-asthenia-strain scale, the study group had significantly better final Voice Handicap Index scores.
Conclusion:
Following surgery for vocal polyps, post-operative voice therapy can improve patients' vocal discomfort, emotional responses and everyday self-perception.
Δ14C values of leaves of deciduous trees provide a means to map the regional-scale fossil fuel ratio in the atmosphere. We collected a batch of ginkgo (Ginkgo biloba Linnaeus, a deciduous tree) leaf samples from across Korea in the month of July in both 2010 and 2011 to obtain the regional distribution of Δ14C. The Δ14C values of the samples were measured using accelerator mass spectrometry (AMS) at the Korea Institute of Geoscience and Mineral Resources (KIGAM). The average of the Δ14C values from clean air sites in Korea in 2011 measured slightly lower than the average of Δ14C values in 2010. Distribution maps of Δ14C of 2011 and 2010 in Korea were made based on a series of Δ14C values of ginkgo leaf samples from Korea using the Geostatistical and Spatial analyst tools in ESRI's ArcMap software. The distribution maps of Δ14C showed that Δ14C values in the western part of Korea are lower than those in the eastern part of Korea. This is because the western part of Korea is densely populated and contains many industrial complexes, and also because westerly winds from China, containing CO2 from fossil fuel use, blow into Korea. We compared the distribution maps of 2010 and 2011 and tried to find traces of the Fukushima power plant accident in Japan.
We investigated the connection between AGN and star formation (SF) activities of various kinds of AGNs and their host galaxies. In order to probe SF activity, we measured the 3.3 μm PAH emission luminosity utilizing the slitless spectroscopic capability of AKARI space telescope. We present the results from two missions, ASCSG and LQSONG.
The development of radiocarbon dating for degraded bone samples collected at Korean archaeological sites has been successful through the characterization of raw bone C/N ratios and application of an ultrafiltration method. It was found that the C/N ratios of raw bone samples are inversely proportional to the carbon content and residue amount after gelatinization. We have examined a few dozen Korean archaeological bone samples for this study. Well-preserved bone samples are found to be physically dense. The range of C/N ratios of Korean raw bone samples ranged from 3.4 to 74. We found that the C/N ratios of degraded raw bone samples can be used to determine whether 14C samples are acceptable for normal pretreatment processing and eventual dating. The results of this study support that even if the C/N ratio of a degraded raw bone sample is 11, extraction of collagen for bone dating is feasible by a carefully designed ultrafiltration process. Our preliminary 14C dating results of a depth profile of Gunang-gul Cave, an archaeological site in Danyang, Korea, indicate that this site has been either geologically or anthropologically disturbed in the past, with 14C ages ranging from 28,910 ± 200 to 48,090 ± 1050 yr BP. The C/N ratios of the collagen samples of Gunang-gul were determined to be 3.2–3.6. Our study establishes a new guide for the pretreatment of degraded bone samples such as those collected in Korea for 14C dating.
Since iron artifacts generally contain trace amounts of carbon, an iron sample needs to be relatively large, as compared to other materials, and a specially designed combustion system is required. An elemental analyzer (EA) was used for the combustion of iron without any special chemical treatment. CO2 gas with 1 mg of carbon was obtained from the combustion of an iron artifact by using an EA and reduced to graphite for accelerator mass spectrometry (AMS) measurement. In this work, AMS dating results done at the Korea Institute of Geoscience and Mineral Resources (KIGAM) for several ancient iron artifacts are presented and compared with independently estimated ages. This method was found to be useful for the pretreatment of iron artifacts that contained >0.1% carbon. A simple pretreatment method using an EA was also applied to calcium carbonate (CaCO3) samples. Samples were preheated overnight at 100–300 °C, without any special chemical treatment. This removed modern CO2 contamination and the background level decreased to a comparable value measured in samples treated with phosphoric acid under vacuum.
The relationship between temperature and time required for collagenization using modern bone samples was investigated. Gelatinized samples of bone collagen were filtered to selectively collect different molecular weight fractions. The results of this study suggest that heating to 70 ° for a duration of 12 hr provides the optimal conditions for gelatinization.