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.

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.

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.

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.

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 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.

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.

Trends in hypertension prevalence, awareness, treatment, and control in South Korea, 1998-2021: a nationally representative serial study.

The impact of the pandemic on hypertension management is unknown, particularly regarding changes in demographic risk factors. We conducted a comprehensive study between 1998 and 2021 on the long-term trends in hypertension prevalence in South Korea, including a comparison of the pre-pandemic and pandemic eras. Data from 1998 to 2021 of 108,687 Korean adults were obtained through a nationwide, large-scale, and serial study. We conducted a weighted complex sampling analysis on the estimates of national prevalence and compared the slope of hypertension prevalence before and during the pandemic to determine the trend dynamics. We included 108,687 participants over 24 years, 1998-2021. While the prevalence of patients with hypertension consistently increased before the pandemic from 25.51% [95% CI: 24.27-26.75] in 1998-2005 to 27.81% [95% CI: 26.97-28.66] in 2016-2019, the increasing slope in hypertension prevalence slowed during the pandemic period (28.07% [95% CI: 26.16-29.98] for 2021; ßdiff, -0.012 [-0.023 to 0.000]). Hypertension awareness, treatment, control, and control rates among patients receiving treatment followed similar trends. Compared to the pre-pandemic era, individuals aged 19-59 years or male had significantly increased control rates among the treated patients during the pandemic. This study investigated long-term trends in hypertension prevalence, awareness, treatment, and control among Korean adults. The absence of a reduction in the health indicators associated with hypertension during the pandemic implies that medical services for individuals with hypertension remain unaffected.

National trends in rheumatoid arthritis and osteoarthritis prevalence in South Korea, 1998-2021.

Studies on the trends in the prevalence of rheumatoid arthritis (RA) and osteoarthritis (OA) are limited, particularly during the COVID-19 pandemic. This study aimed to analyze the temporal trend of RA and OA in South Korean adults from 1998 to 2021, including the COVID-19 pandemic period. The Korea National Health and Nutrition Examination Survey (KNHANES) data on adults aged ≥ 19 years were analyzed to investigate the prevalence of RA and OA from 1998 to 2021. The prevalence trends were compared by the years, and ßdiff (ß difference) was calculated. Odds ratios (ORs) were computed for each disease to examine changes in disease prevalence before and during the pandemic in order to determine the impact of the pandemic on disease prevalence. Among 163,221 Korean adults, the prevalence of RA and OA showed a steady decrease from 2005 (RA: from 1.91% in 2005-2007 to 1.55% in 2016-2019 and OA: from 9.75% in 2005-2007 to 8.27% in 2016-2019), but there was a slight increased after the onset of the COVID-19 pandemic (RA: from 1.23% in 2020 to 1.36% in 2021 and OA: from 8.04% in 2020 to 8.27% in 2021). Vulnerable groups, including participants aged ≥ 60 years (versus 19-60 years, ratio of ORs: 1.222; 95% CI 1.011-1.477), urban residents (ratio of ORs: 1.289; 95% CI 1.007-1.650), and participants with higher education level (ratio of ORs: 1.360; 95% CI 1.119-1.653) showed higher ORs of OA, whereas no particularly vulnerable population was observed for RA. Our findings provide an insight into the long-term trends of RA and OA among adult population and highlight a novel perspective on the impact of COVID-19 on disease prevalence.

Global incidence and prevalence of autoimmune hepatitis, 1970-2022: a systematic review and meta-analysis.

Background: Autoimmune hepatitis (AIH) varies significantly in incidence and prevalence across countries and regions. We aimed to examine global, regional, and national trends in incidence and prevalence of AIH from 1970 to 2022. Methods: We conducted a thorough search of the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from database inception to August 9, 2023, using the search term "autoimmune hepatitis" in combination with "incidence," "prevalence," or "trend." Only general population-based observational studies with larger samples sizes were considered for inclusion. Studies that recruited convenience samples, and those with fewer than 50 participants were excluded. Summary data were extracted from published reports. A random effects model was used and pooled estimates with 95% CI were used to calculate the incidence and prevalence of AIH. Heterogeneity was evaluated using the I2 statistic. The study protocol was registered with PROSPERO, CRD42023430138. Findings: A total of 37 eligible studies, encompassing more than 239 million participants and 55,839 patients with AIH from 18 countries across five continents, were included in the analysis. Global pooled incidence and prevalence of AIH were found to be 1.28 cases per 100,000 inhabitant-years (95% CI, 1.01-1.63, I2 = 99·51%; number of studies, 33; sample population, 220,673,674) and 15.65 cases per 100,000 inhabitants (95% CI, 13.42-18.24, I2 = 99·75%; number of studies, 26; sample population, 217,178,684), respectively. The incidence of AIH was greater in countries with high Human Development Index (>0.92), in North America and Oceania (compared with Asia), among females, adults (compared with children), and high latitude (>45°). Similar patterns in AIH prevalence were observed. Pooled AIH prevalence increased gradually from 1970 to 2019 (1970-1999; 9.95 [4.77-15.13], I2 = 95·58% versus 2015-2022; 27.91 [24.86-30.96], I2 = 99·32%; cases per 100,000 inhabitants). The overall incidence and prevalence of AIH, as well as some subgroup analyses of the studies, displayed asymmetry in the funnel plots, suggesting potential evidence of publication bias. Interpretation: AIH incidence and prevalence have increased significantly and exhibit substantial variation across regions worldwide. Further research is required to assess the incidence and prevalence of AIH, specifically in South America and Africa. Funding: National Research Foundation of Korea.

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 .

Viral load dynamics and shedding kinetics of mpox infection: a systematic review and meta-analysis.

BACKGROUND: Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral dynamics of mpox remains limited and inconclusive. Thus, we aimed to provide a comprehensive understanding of the viral load and viability of the re-emerged mpox virus since 2022. METHODS: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase and Google Scholar for published articles that are related to mpox viral dynamics up to April 2023. RESULTS: From 19 studies, 880 samples and 1477 specimens were collected. The pooled median Ct values appeared in the following order: skin lesion [Ct value 21.7 (IQR 17.8-25.5)], anorectal [22.3 (16.9-27.6)], saliva [25.9 (22.5-31.1)], oral [29.0 (24.5-32.8)], semen [29.6 (25.9-33.4)], urine [30.5 (24.6-36.4)], pharyngeal [31.9 (26.5-37.3)], urethra [33.0 (28.0-35.0)] and blood [33.2 (30.4-36.1)]. People living with human immunodeficiency virus (HIV) have a lower Ct value in the skin [skin HIV+, 19.2 (18.3-20.0) vs skin HIV-, 25.4 (21.2-29.0)]. From the Ct values and test day since symptom onset, we identified temporal trends of viral load for each specimen type. Changes in the trend were observed at 4 days in saliva, 5 days in blood, 6 days in skin, 7 days in anorectal, urine, semen and pharyngeal and 8 days in the urethra. We determined optimal Ct cutoff values for anorectal (34.0), saliva (27.7) and urethra (33.0) specimens, where a Ct value above each cutoff suggests minimal viral viability. Using these cutoff values, we derived the duration of viable viral isolation in each specific specimen type (anorectal 19 days, saliva 14 days and urethra 14 days). CONCLUSION: Skin lesion, anorectal and saliva samples contained the highest viral load. The peak viral load manifests within 4-8 days after symptom onset, and viable virus detection was presumed to cease within 14-19 days from symptom onset in anorectal, saliva and urethral samples.

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.

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.