Effects and safety of transcranial direct current stimulation on multiple health outcomes: an umbrella review of randomized clinical trials.

Transcranial direct current stimulation (tDCS), which delivers a direct current to the brain, emerged as a non-invasive potential therapeutic in treating a range of neurological and neuropsychiatric disorders. However, a comprehensive quantitative evidence synthesis on the effects of tDCS on a broad range of mental illnesses is lacking. Here, we systematically assess the certainty of the effects and safety of tDCS on several health outcomes using an umbrella review of randomized controlled trials (RCTs). The methodological quality of each included original meta-analysis was assessed by the A Measurement Tool for Assessing Systematic Reviews 2 (AMSTAR2), and the certainty of the evidence for each effect was evaluated with Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). We followed an a priori protocol (PROSPERO CRD42023458700). We identified 15 meta-analyses of RCTs (AMSTAR 2; high 3, moderate 3, and low 9) that included 282 original articles, covering 22 unique health endpoints across 22 countries and six continents. From meta-analyses of RCTs supported by very low to high certainty of evidence, it was found that tDCS improved symptoms related to post-stroke, including post-stroke depression scale score (equivalent standardized mean difference [eSMD], 1.61 [95% confidence level, 0.72-2.50]; GRADE=moderate), activities of daily living independence (7.04 [3.41-10.67]; GRADE=high), motor recovery of upper and lower extremity (upper extremity: 0.15 [0.06-0.24], GRADE=high; lower extremity: 0.10 [0.03-0.16], GRADE=high), swallowing performance (GRADE=low), and spasticity (GRADE=moderate). In addition, tDCS had treatment effects on symptoms of several neurological and neuropsychiatric disorders, including obsessive-compulsive disorder (0.81 [0.44-1.18]; GRADE=high), pain in fibromyalgia (GRADE=low), disease of consciousness (GRADE=low), insight score (GRADE=moderate) and working memory (0.34 [0.01-0.67]; GRADE=high) in schizophrenia, migraine-related pain (-1.52 [-2.91 to -0.13]; GRADE=high), attention-deficit/hyperactivity disorder (reduction in overall symptom severity: 0.24 [0.04-0.45], GRADE=low; reduction in inattention: 0.56 [0.02-1.11], GRADE=low; reduction in impulsivity: 0.28 [0.04-0.51], GRADE=low), depression (GRADE=low), cerebellar ataxia (GRADE=low), and pain (GRADE=very low). Importantly, tDCS induced an increased number of reported cases of treatment-emergent mania or hypomania (0.88 [0.62-1.13]; GRADE=moderate). We found varied levels of evidence for the effects of tDCS with multiple neurological and neuropsychiatric conditions, from very low to high certainty of evidence. tDCS was effective for people with stroke, obsessive-compulsive disorder, fibromyalgia, disease of consciousness, schizophrenia, migraine, attention-deficit/hyperactivity disorder, depression, cerebellar ataxia, and pain. Therefore, these findings suggest the benefit of tDCS for several neurological and neuropsychiatric disorders; however, further studies are needed to understand the underlying mechanism and optimize its therapeutic potential.

Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study.

BACKGROUND: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. OBJECTIVE: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. DESIGN: Binational, longitudinal, propensity-matched cohort study. SETTING: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). PARTICIPANTS: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. MEASUREMENTS: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. RESULTS: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. LIMITATIONS: Referral bias due to the pandemic; residual confounding. CONCLUSION: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. PRIMARY FUNDING SOURCE: National Research Foundation of Korea.

Global burden of vaccine-associated anaphylaxis and their related vaccines, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

BACKGROUND: Vaccine-associated anaphylaxis is a rare but life-threatening reaction that occurs within minutes to hours of exposure to allergens. As studies utilizing large-scale data to investigate this topic are limited, further research is needed to assess its burden, long-term trends, and associated risk factors so as to gain a comprehensive understanding of vaccine-associated anaphylaxis globally. Therefore, this study aimed to investigate the global burden of vaccine-associated anaphylaxis and related vaccines. METHOD: This study utilized the World Health Organization International Pharmacovigilance Database, in which reports of vaccine-associated anaphylaxis between 1967 and 2023 were obtained (total reports = 131,255,418). We estimated the global reporting counts, reported odds ratio (ROR), and information component (IC) to identify the relationship between 19 vaccines and associated anaphylaxis in 156 countries and territories. RESULTS: We identified 31,676 reports of vaccine-associated anaphylaxis among 363,290 reports of all-cause anaphylaxis. The cumulative number of reports on vaccine-associated anaphylaxis has gradually increased over time, with a dramatic increase after 2020, owing to reports of COVID-19 mRNA vaccine-associated anaphylaxis. The typhoid vaccines were associated with the most anaphylactic reports (ROR: 4.35; IC0.25 : 1.86), followed by encephalitis (3.27; 1.45), hepatitis B (2.69; 1.30), cholera (2.65; 0.54), hepatitis A (2.44; 1.12), influenza (2.36; 1.16), inactivated whole-virus COVID-19 (2.21; 1.02), and COVID-19 mRNA vaccines (1.89; 0.79). In terms of age- and sex-specific risks, vaccine-associated anaphylaxis reports develop more frequently in females and at young ages. The Ad5-vectored COVID-19 vaccine anaphylaxis reports were associated with the highest fatality rate (15.0%). CONCLUSIONS: Although multiple vaccines are associated with various spectra and risks of anaphylaxis, clinicians should recognize the possibility of anaphylaxis occurring with all vaccines, particularly the COVID-19 mRNA and inactivated whole-virus COVID-19 vaccines, and consider the risk factors associated with vaccine anaphylaxis reports. Further studies are warranted to identify better ways of preventing vaccine-associated anaphylaxis.

National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021.

INTRODUCTION: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. METHOD: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained ß-coefficients with 95% confidence intervals (CI). RESULTS: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57-6.10) in 1998-2005 to 8.99% (8.09-9.91) in 2021 and CRS from 1.84% (1.70-1.97) in 1998-2005 to 3.70% (3.18-4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. CONCLUSIONS: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.

National Trends and Prevalence of Atopic Dermatitis and Pandemic-Related Factors among Korean Adults, 2007-2021.

INTRODUCTION: Previous studies have variably reported inconclusive trends in the prevalence of atopic dermatitis (AD) among adults, and there are limited data on the impact of the COVID-19 pandemic. We aimed to investigate the national trends and age-stratified prevalence of AD among adults from 2007 to 2021 in South Korea, focusing mainly on the impact of the COVID-19 pandemic-related factors. METHODS: A nationwide cross-sectional study was conducted using the Korea National Health and Nutrition Examination Survey data from 2007 to 2021. Overall and age-stratified prevalence for AD were assessed using weighted beta coefficients or odds ratios. RESULTS: A total of 83,566 adults over 20 years (male, 49.40%) were included. During the observation period, the prevalence of AD was stable in the overall population from 2.61% (95% CI, 2.29-2.93) in 2007-2009 to 2.15% (1.68-2.63) in 2020 and 2.38% (1.81-2.95) in 2021. However, the weighted prevalence of AD in adults aged 40-59 years old decreased during the pre-pandemic era, and the prevalence of AD in adults aged above 60 years significantly decreased during the pandemic, with a significant decline observed after the initial outbreak. From age-stratification analysis, the adults aged 40-59 years showed a significant increase after the pandemic outbreak which was evident in specific variables: individuals with rural residence, lower education, and lower household income quartiles. Adults aged above 60 years showed a significant decrease in the slope after the outbreak, evident in specific variables: individuals of female, rural residence, lower education, and lower household income quartiles. CONCLUSION: We observed a stable overall prevalence of AD throughout the 15-year observation period. However, the age-stratified analysis suggested significantly different trends according to age-stratified groups and the impact of the COVID-19 pandemic on the prevalence of AD.

Global, Regional, and National Burden of Spine Pain, 1990-2019: A Systematic Analysis of the Global Burden of Disease Study 2019.

OBJECTIVE: To describe the global, regional, national, and temporal trends in neck pain (NP) and low back pain (LBP) from 1990 to 2019 and analyze associations with age, sex, and sociodemographic index (SDI). DESIGN: Temporal trends analyses of the Global Burden of Disease 2019 data for global, regional, and national prevalence, incidence, and years lived with disabilities (YLDs) of NP and LBP from 1990 to 2019. SETTING: Not applicable. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE(S): The temporal trends in prevalence, incidence, and YLDs of NP and LBP, and associations with age, sex, and SDI. RESULTS: Globally, the prevalence, incidence, and YLDs of NP and LBP significantly increased; however, the age-standardized rates of NP showed a stable trend, and those of LBP slightly decreased from 1990 to 2019. The burden of NP and LBP was higher in women than in men. Both NP and LBP exhibited similar age-related trends, with the total numbers and rates increasing with age and reaching their highest points in the middle- and old-aged groups, respectively, in 2019. Overall, the prevalence, incidence, and YLDs of NP and LBP were higher in regions with higher SDI over the 3 decades. CONCLUSIONS: NP and LBP impose significant major public health burden globally. Although both conditions are more frequent in women and middle-aged groups and tend to be prevalent in countries with high SDI, they have distinct temporal and regional patterns. By comprehending temporospatial trends in the disease burden of NP and LBP, policymakers and health care professionals can make future interventions and policies to effectively manage these conditions worldwide as well as to achieve equity in prevention, diagnosis, and treatment.

Machine Learning-Based Prediction of Suicidal Thinking in Adolescents by Derivation and Validation in 3 Independent Worldwide Cohorts: Algorithm Development and Validation Study.

BACKGROUND: Suicide is the second-leading cause of death among adolescents and is associated with clusters of suicides. Despite numerous studies on this preventable cause of death, the focus has primarily been on single nations and traditional statistical methods. OBJECTIVE: This study aims to develop a predictive model for adolescent suicidal thinking using multinational data sets and machine learning (ML). METHODS: We used data from the Korea Youth Risk Behavior Web-based Survey with 566,875 adolescents aged between 13 and 18 years and conducted external validation using the Youth Risk Behavior Survey with 103,874 adolescents and Norway's University National General Survey with 19,574 adolescents. Several tree-based ML models were developed, and feature importance and Shapley additive explanations values were analyzed to identify risk factors for adolescent suicidal thinking. RESULTS: When trained on the Korea Youth Risk Behavior Web-based Survey data from South Korea with a 95% CI, the XGBoost model reported an area under the receiver operating characteristic (AUROC) curve of 90.06% (95% CI 89.97-90.16), displaying superior performance compared to other models. For external validation using the Youth Risk Behavior Survey data from the United States and the University National General Survey from Norway, the XGBoost model achieved AUROCs of 83.09% and 81.27%, respectively. Across all data sets, XGBoost consistently outperformed the other models with the highest AUROC score, and was selected as the optimal model. In terms of predictors of suicidal thinking, feelings of sadness and despair were the most influential, accounting for 57.4% of the impact, followed by stress status at 19.8%. This was followed by age (5.7%), household income (4%), academic achievement (3.4%), sex (2.1%), and others, which contributed less than 2% each. CONCLUSIONS: This study used ML by integrating diverse data sets from 3 countries to address adolescent suicide. The findings highlight the important role of emotional health indicators in predicting suicidal thinking among adolescents. Specifically, sadness and despair were identified as the most significant predictors, followed by stressful conditions and age. These findings emphasize the critical need for early diagnosis and prevention of mental health issues during adolescence.

Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976-2022: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Owing to 2018 expanded diagnostic criteria for eosinophilic esophagitis (EoE) and thus a possible increase in diagnosis, previous studies on the global incidence and prevalence of EoE may need to be updated. We aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2022 and analyze their associations with geographic, demographic, and social factors through a systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from their inception dates to December 20, 2022, for studies that reported the incidence or prevalence of EoE in the general population. We calculated the global incidence and prevalence of EoE using pooled estimates with 95% confidence intervals (CIs) and performed subgroup analysis based on age, sex, race, geographical area, World Bank income group, and diagnostic criteria of EoE. RESULTS: Forty studies met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents. The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years (95% CI, 3.98-6.63; number of studies, 27; sample population, 42,191,506) and 40.04 cases per 100,000 inhabitant-years (95% CI, 31.10-48.98; number of studies, 20; sample population, 30,467,177), respectively. The pooled incidence of EoE was higher in high-income countries (vs low- or middle-income countries), males, and North America (vs Europe and Asia). The global prevalence of EoE followed a similar pattern. The pooled prevalence of EoE gradually increased from 1976 to 2022 (1976-2001; 8.18; 95% CI, 3.67-12.69 vs 2017-2022; 74.42; 95% CI, 39.66-109.19 cases per 100,000 inhabitant-years). CONCLUSIONS: The incidence and prevalence of EoE have increased substantially and vary widely across the world. Further research is needed to evaluate the incidence and prevalence of EoE in Asia, South America, and Africa.

Comparison of clinical manifestations in mpox patients living with HIV versus without HIV: A systematic review and meta-analysis.

Currently, many cases of mpox patients living with the human immunodeficiency virus (HIV) have been reported. Immunocompromised mpox patients, including those living with HIV are noted for an increased risk for severe symptoms; however, existing studies did not focus on the statistical comparison of mpox outcomes associated with HIV. Thus, we conducted a systematic review and meta-analysis to evaluate and compare the clinical manifestations of mpox in people living with HIV (PLWH) and people without HIV. In this systematic review and meta-analysis, PubMed/MEDLINE, Embase, and Google Scholar were searched up to March 7, 2023. A random effects model was used to calculate the pooled prevalence along with the 95% confidence intervals (CI), and the odds ratio and its corresponding 95% CIs were calculated to elucidate the significance of each clinical feature for mpox patients with and without HIV. In this study, we included 99 published papers with 2413 patients with mpox (median age, 35.5 years; PLWH n = 1151) from 27 countries across six continents. The odds ratio of the mpox outcomes with PLWH in comparison to patients without HIV was found to be significant for skin rash (1.24, 95% CI: 1.01-1.53), proctitis (2.03, 95% CI: 1.36-3.04), cough (0.57, 95% CI: 0.33-0.98), and diarrhea (3.85, 95% CI: 1.24-11.98). The odds ratio of mpox patients with HIV for historical infections of syphilis was 2.14 (95% CI: 1.38-3.32), compared with those without HIV. This is the first international and comprehensive study that performed a systematic review and meta-analysis to statistically measure mpox manifestations according to HIV status. As clinical features related to mucosal contact were characteristically pronounced in PLWH, our systematic review provides insight that the primary invasion site of infection strongly relates to the outcomes of mpox.

National trends in physical activity among adolescents in South Korea before and during the COVID-19 pandemic, 2009-2021.

With the ongoing COVID-19 pandemic, several previous studies from different countries showed that physical activity (PA) decreased during the COVID-19 outbreak. However, few studies have examined the recent tendency of PA in the adolescent population. Thus, we aimed to investigate the long-term trend of PA in Korean youth and the prevalence changes between before and during the COVID-19 pandemic. Data from Korea Youth Risk Behavior Web-Based Survey (KYRBS) was collected for consecutive years between 2009 and 2021. The period was separated into prepandemic (2009-2019), early-pandemic (2020), and mid-pandemic (2021). Self-reported amount of PA was categorized into four groups (insufficient, aerobic, muscle strengthening, and both physical activities) according to World Health Organization (WHO) PA guidelines. A total of 840 488 adolescents aged 12-18 who fully responded to the survey were selected (response rate: 95.2%). The 13-year trends in the proportion of adolescents who reported aerobic and muscle-strengthening activities met or exceeded 2020 WHO exercise guidelines for adolescents plateaued (11.9% from 2009 to 2011, 14.2% from 2018 to 2019, 14.4% from 2020, and 14.0% from 2021); however, the slope decreased during the pandemic (ßdiff , -0.076; 95% confidence interval [CI], -0.123 to -0.029). Proportion of sufficient aerobic exercise among adolescents sharply decreased midst the pandemic (28.0% from 2009 to 2011, 29.4% from 2018 to 2019, and 23.8% from 2020; ßdiff , -0.266; 95% CI, -0.306 to -0.226) but increased again in 2021 (26.0% from mid-COVID 19; 95% CI, 25.4-26.7). Similar patterns were observed in Metabolic Equivalent Task (MET) score (MET-min/week; 804.1 from 2018 to 2019, 720.9 from 2020, and 779.6 from 2021). The mean difference in MET score between pre-COVID and post-COVID was -55.4 MET-min/week (95% CI, -70.5 to -40.3). Through a nationwide representative study, there was no significant difference with regard to the number of Korean adolescents who achieved the PA guidelines (pre and postpandemic); however, the prevalence of recommended levels of PA needs to increase more based on the trend before the COVID-19 outbreak. The findings of this study suggest reinforcement of the importance of public health policies for Korean youths to be more physically active, especially during and after the pandemic.

Global, regional, and national burden of allergic disorders and their risk factors in 204 countries and territories, from 1990 to 2019: A systematic analysis for the Global Burden of Disease Study 2019.

BACKGROUND: Asthma and atopic dermatitis (AD) are chronic allergic conditions, along with allergic rhinitis and food allergy and cause high morbidity and mortality both in children and adults. This study aims to evaluate the global, regional, national, and temporal trends of the burden of asthma and AD from 1990 to 2019 and analyze their associations with geographic, demographic, social, and clinical factors. METHODS: Using data from the Global Burden of Diseases (GBD), Injuries, and Risk Factors Study 2019, we assessed the age-standardized prevalence, incidence, mortality, and disability-adjusted life years (DALYs) of both asthma and AD from 1990 to 2019, stratified by geographic region, age, sex, and socio-demographic index (SDI). DALYs were calculated as the sum of years lived with disability and years of life lost to premature mortality. Additionally, the disease burden of asthma attributable to high body mass index, occupational asthmagens, and smoking was described. RESULTS: In 2019, there were a total of 262 million [95% uncertainty interval (UI): 224-309 million] cases of asthma and 171 million [95% UI: 165-178 million] total cases of AD globally; age-standardized prevalence rates were 3416 [95% UI: 2899-4066] and 2277 [95% UI: 2192-2369] per 100,000 population for asthma and AD, respectively, a 24.1% [95% UI: -27.2 to -20.8] decrease for asthma and a 4.3% [95% UI: 3.8-4.8] decrease for AD compared to baseline in 1990. Both asthma and AD had similar trends according to age, with age-specific prevalence rates peaking at age 5-9 years and rising again in adulthood. The prevalence and incidence of asthma and AD were both higher for individuals with higher SDI; however, mortality and DALYs rates of individuals with asthma had a reverse trend, with higher mortality and DALYs rates in those in the lower SDI quintiles. Of the three risk factors, high body mass index contributed to the highest DALYs and deaths due to asthma, accounting for a total of 3.65 million [95% UI: 2.14-5.60 million] asthma DALYs and 75,377 [95% UI: 40,615-122,841] asthma deaths. CONCLUSIONS: Asthma and AD continue to cause significant morbidity worldwide, having increased in total prevalence and incidence cases worldwide, but having decreased in age-standardized prevalence rates from 1990 to 2019. Although both are more frequent at younger ages and more prevalent in high-SDI countries, each condition has distinct temporal and regional characteristics. Understanding the temporospatial trends in the disease burden of asthma and AD could guide future policies and interventions to better manage these diseases worldwide and achieve equity in prevention, diagnosis, and treatment.

Safety and Efficacy of Poly-L-Lactic Acid Filler (Gana V vs. Sculptra) Injection for Correction of the Nasolabial Fold: A Double-Blind, Non-Inferiority, Randomized, Split-Face Controlled Trial.

BACKGROUND: Poly-L-lactic acid (PLLA) fillers have shown excellent results as soft tissue fillers for progressive midface volume enhancement, with long-lasting results and high patient satisfaction. OBJECTIVE: Herein, we investigated the safety and effectiveness of a new PLLA filler (Gana V) in comparison with those of the widely used Sculptra. METHODS: This double-blind, non-inferiority, randomized, split-face controlled trial was performed in France to evaluate the safety and effectiveness of injectable Gana V compared with those of Sculptra for correction of nasolabial fold (NLF) depression. The primary outcome was improvement in NLFs, as determined using the Wrinkle Severity Rating Scale (WSRS). This trial is an interim report of the results at 6 months. The trial was registered at ClinicalTrials. gov, number NCT05215054. RESULTS: Fifty-five participants with moderate-to-severe NLFs (mean age 53.8 [standard deviation 8.7] years; 48 [87.3%]) female) were enrolled. After 6 months, Gana V showed improved WSRS score (mean difference - 0.25; 95% confidence interval [CI] - 0.49 to - 0.01) in intention-to-treat analysis, while Sculptra did not (mean difference - 0.20; 95% CI - 0.42 to 0.03). Furthermore, Gana V showed an acceptable 6-month effectiveness compared with Sculptra, within our defined non-inferiority margin (pnon-inferiority = 0.1787). The immediate results by the investigator after the initial injection showed higher satisfaction in the Gana V than in the Sculptra group. Gana V and Sculptra showed no difference in adverse reactions. Similar patterns were observed in per-protocol analyses. CONCLUSIONS: Gana V is non-inferior to Sculptra with respect to the correction of NLFs and has higher investigator satisfaction. Further research is required to ensure long-term safety. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Comorbid physical health outcomes in patients with bipolar disorder: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: Although several meta-analyses have examined the association between bipolar disorder (BD) and its comorbid health outcomes, this evidence has not been comprehensively assembled. OBJECTIVE: We aimed to systematically review existing meta-analyses based on multiple physical outcomes and validate the evidence level by examining the existing certainty of evidence. METHODS: We systematically searched databases, including PubMed/MEDLINE, Embase, Google Scholar, and CINAHL, for articles published up to July 2023. We included meta-analyses of cohort, case-control, and/or cross-sectional studies investigating any comorbid health outcomes in patients with BD. We conducted quality assessments of the included meta-analysis using AMSTAR2. The credibility of findings was categorized into five levels of class and quality of evidence (CE), including convincing, highly suggestive, suggestive, weak, or not significant. RESULTS: We analyzed 12 meta-analyses, including 145 original articles, covering 14 unique health outcomes with over 60 million participants across 29 countries and five continents. Among 14 health outcomes, BD was significantly associated with eight comorbid health outcomes, including dementia (equivalent odds ratio [eOR], 2.96 [95 % confidence intervals {CI}, 1.69-5.17]; CE=suggestive), Parkinson's disease (3.35 [1.72-6.53]; CE=suggestive), asthma (1.86 [1.42-2.42]; CE=weak), toxoplasmosis (1.69 [1.21-2.37]; CE=weak), hypertension (1.28 [1.02-1.60]; CE=convincing), breast cancer (1.33 [1.15-1.55]; CE=weak), obesity (1.64 [1.30-1.99]; CE=suggestive), and type 2 diabetes mellitus (1.98 [1.55-2.52]; CE=weak). CONCLUSION: Individuals with BD are predisposed to numerous comorbid physical conditions, though these links are supported by various evidence levels and necessitate further studies. It is imperative that physicians be aware of these potential comorbidities in patients with BD and take proactive measures to manage them.

Short- and long-term neuropsychiatric outcomes in long COVID in South Korea and Japan.

We investigated whether SARS-CoV-2 infection is associated with short- and long-term neuropsychiatric sequelae. We used population-based cohorts from the Korean nationwide cohort (discovery; n = 10,027,506) and the Japanese claims-based cohort (validation; n = 12,218,680) to estimate the short-term (<30 days) and long-term (≥30 days) risks of neuropsychiatric outcomes after SARS-CoV-2 infection compared with general population groups or external comparators (people with another respiratory infection). Using exposure-driven propensity score matching, we found that both the short- and long-term risks of developing neuropsychiatric sequelae were elevated in the discovery cohort compared with the general population and those with another respiratory infection. A range of conditions including Guillain-Barré syndrome, cognitive deficit, insomnia, anxiety disorder, encephalitis, ischaemic stroke and mood disorder exhibited a pronounced increase in long-term risk. Factors such as mild severity of COVID-19, increased vaccination against COVID-19 and heterologous vaccination were associated with reduced long-term risk of adverse neuropsychiatric outcomes. The time attenuation effect was the strongest during the first six months after SARS-CoV-2 infection, and this risk remained statistically significant for up to one year in Korea but beyond one year in Japan. The associations observed were replicated in the validation cohort. Our findings contribute to the growing evidence base on long COVID by considering ethnic diversity.

National prevalence of atopic dermatitis in Korean adolescents from 2009 to 2022.

Previous studies have examined the prevalence of allergic diseases in adolescents 1-2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the ß difference (ßdiff) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66-6.91) in 2009-2011 to 6.89% (95% CI 6.72-7.05) in 2018-2019, then decreased slightly to 5.82% (95% CI 5.60-6.04) in 2022. Across the 14 years, middle school student status, low parent's highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic.

Effectiveness of famotidine on the risk of poor prognosis in patients with COVID-19: A nationwide cohort study in Korea.

Objective: Famotidine has been proposed as a promising candidate for the treatment of coronavirus disease 2019 (COVID-19). However, there is limited research on the association of famotidine with the poor prognosis of COVID-19. Methods: The Korean nationwide cohort included 6,556 patients who tested positive on RT-PCR for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The poor COVID-19-related outcomes were defined on the basis of having encountered the composite outcome of high oxygen therapy, intensive care unit admission, administration of mechanical ventilation, or death. In addition, we performed exposure-driven propensity score matching for no H2-blocker use versus current famotidine use, and other H2-blocker use versus current famotidine use. Results: 4,785 (73.0%) patients did not use a H2-blocker, 393 (6.0%) patients were currently used famotidine, and 1,292 (19.7%) patients currently used H2-blocker other than famotidine. In multivariable analysis after matching (no H2-blocker use versus current famotidine use), there was no significant association between current famotidine use and composite outcomes (adjusted odd ratios [aOR]: 1.30, 95% confidence interval [CI]: 0.55-3.06). On the other hand, another matched cohort (other H2-blocker use versus current famotidine use), demonstrated a positive association between current famotidine use and composite outcomes (aOR: 3.56, 95% CI: 1.03-12.28). Conclusions: Our study results did not support the potential of famotidine as a therapeutic agent for COVID-19. A rather unexpected result could be observed in the comparisons between current famotidine use and other H2-blocker use; it was observed that current famotidine use increased the risk of poor COVID-19 related outcomes. Further studies are needed to clearly prove the causal relationship with several H2-blockers, including famotidine.

Quantification of identifying cognitive impairment using olfactory-stimulated functional near-infrared spectroscopy with machine learning: a post hoc analysis of a diagnostic trial and validation of an external additional trial.

BACKGROUND: We aimed to quantify the identification of mild cognitive impairment and/or Alzheimer's disease using olfactory-stimulated functional near-infrared spectroscopy using machine learning through a post hoc analysis of a previous diagnostic trial and an external additional trial. METHODS: We conducted two independent, patient-level, single-group, diagnostic interventional trials (original and additional trials) involving elderly volunteers (aged > 60 years) with suspected declining cognitive function. All volunteers were assessed by measuring the oxygenation difference in the orbitofrontal cortex using an open-label olfactory-stimulated functional near-infrared spectroscopy approach, medical interview, amyloid positron emission tomography, brain magnetic resonance imaging, Mini-Mental State Examination, and Seoul Neuropsychological Screening Battery. RESULTS: In total, 97 (original trial) and 36 (additional trial) elderly volunteers with suspected decline in cognitive function met the eligibility criteria. The statistical model reported classification accuracies of 87.3% in patients with mild cognitive impairment and Alzheimer's disease in internal validation (original trial) but 63.9% in external validation (additional trial). The machine learning algorithm achieved 92.5% accuracy with the internal validation data and 82.5% accuracy with the external validation data. For the diagnosis of mild cognitive impairment, machine learning performed better than statistical methods with internal (86.0% versus 85.2%) and external validation data (85.4% versus 68.8%). INTERPRETATION: In two independent trials, machine learning models using olfactory-stimulated oxygenation differences in the orbitofrontal cortex were superior in diagnosing mild cognitive impairment and Alzheimer's disease compared to classic statistical models. Our results suggest that the machine learning algorithm is stable across different patient groups and increases generalization and reproducibility. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) of Republic of Korea; CRIS numbers, KCT0006197 and KCT0007589.