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

Vaccine-associated rheumatic diseases are rare but one of the most feared adverse drug reactions (ADRs). However, this topic has been investigated less with large-scale data in the literature. With the rapid progress in the development and approval of vaccines during the pandemic, public concerns regarding their safety have been raised. To assess the global and regional burden, long-term trends, and potential risk factors of vaccines-associated six types of rheumatic diseases (ankylosing spondylitis [AS], polymyalgia rheumatica [PMR], rheumatoid arthritis [RA], Sjögren's syndrome, Systemic lupus erythematosus [SLE], Systemic scleroderma), this study conducted disproportionality analysis based on the reports from the World Health Organization International Pharmacovigilance Database documented between 1967 and 2023 (n for total reports = 131 255 418) across 156 countries and territories. We estimated the reporting odds ratio (ROR) and information component (IC) to determine the disproportionality signal for rheumatic diseases. Of 198 046 reports of all-cause rheumatic diseases, 14 703 reports of vaccine-associated rheumatic diseases were identified. While the reporting counts have gradually increased over time globally, we observed a dramatic increase in reporting counts after 2020, potentially due to a large portion of reports of COVID-19 mRNA vaccine-associated rheumatic diseases. The disproportionality signal for rheumatic diseases was most pronounced in HBV vaccines (ROR, 4.11; IC025, 1.90), followed by COVID-19 mRNA (ROR, 2.79; IC025, 1.25), anthrax (ROR, 2.52; IC025, 0.76), papillomavirus (ROR, 2.16; IC025, 0.95), encephalitis (ROR, 2.01; IC025, 0.58), typhoid (ROR, 1.91; IC025, 0.44), influenza (ROR, 1.49; IC025, 0.46), and HAV vaccines (ROR, 1.41; IC025, 0.20). From age- and sex-specific perspective, young females and old males are likely to have vaccine-associated rheumatic disease reports. Furthermore, overall vaccines showed a disproportionality signal for PMR (IC025, 3.13) and Sjögren's syndrome (IC025, 0.70), systemic scleroderma (IC025, 0.64), specifically while the COVID-19 mRNA vaccines are associated with all six types of diseases. Although multiple vaccines are associated with rheumatic disease reports, healthcare providers should be aware of the potential of autoimmune manifestations following vaccination, particularly the COVID-19 mRNA and HBV vaccines, and take into account for risk factors associated with these ADRs. Most ADRs exhibited an average time to onset of 11 days, underscoring the significance of monitoring and timely management by clinicians.

Prevalence, Awareness, Treatment, and Control of Type 2 Diabetes in South Korea (1998 to 2022): Nationwide Cross-Sectional Study.

BACKGROUND: Type 2 diabetes poses an increasing disease burden in South Korea. The development and management of type 2 diabetes are closely related to lifestyle and socioeconomic factors, which have undergone substantial changes over the past few decades, including during the COVID-19 pandemic. OBJECTIVE: This study aimed to investigate long-term trends in type 2 diabetes prevalence, awareness, treatment, and control. It also aimed to determine whether there were substantial alterations in the trends during the pandemic and whether these changes were more pronounced within specific demographic groups. METHODS: This study examined the prevalence, awareness, treatment, and control of type 2 diabetes in a representative sample of 139,786 South Koreans aged >30 years, using data from the National Health and Nutrition Examination Survey and covering the period from 1998 to 2022. Weighted linear regression and binary logistic regression were performed to calculate weighted ß coefficients or odds ratios. Stratified analyses were performed based on sex, age, region of residence, obesity status, educational background, household income, and smoking status. ß (difference) was calculated to analyze the trend difference between the prepandemic period and the COVID-19 pandemic. To identify groups more susceptible to type 2 diabetes, we estimated interaction terms for each factor and calculated weighted odds ratios. RESULTS: From 1998 to 2022, a consistent increase in the prevalence of type 2 diabetes was observed among South Koreans, with a notable rise to 15.61% (95% CI 14.83-16.38) during the pandemic. Awareness followed a U-shaped curve, bottoming out at 64.37% (95% CI 61.79-66.96) from 2013 to 2015 before increasing to 72.56% (95% CI 70.39-74.72) during the pandemic. Treatment also increased over time, peaking at 68.33% (95% CI 65.95-70.71) during the pandemic. Control among participants with diabetes showed no substantial change, maintaining a rate of 29.14% (95% CI 26.82-31.47) from 2020 to 2022, while control among treated participants improved to 30.68% (95% CI 27.88-33.48). During the pandemic, there was a steepening of the curves for awareness and treatment. However, while the slope of control among participants being treated increased, the slope of control among participants with diabetes showed no substantial change during the pandemic. Older populations and individuals with lower educational level exhibited less improvement in awareness and control trends than younger populations and more educated individuals. People with lower income experienced a deceleration in prevalence during the pandemic. CONCLUSIONS: Over the recent decade, there has been an increase in type 2 diabetes prevalence, awareness, treatment, and control. During the pandemic, a steeper increase in awareness, treatment, and control among participants being treated was observed. However, there were heterogeneous changes across different population groups, underscoring the need for targeted interventions to address disparities and improve diabetes management for susceptible populations.

Association between glucagon-like peptide-1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database.

AIM: To evaluate the potential association between suicidality and glucagon-like peptide-1 receptor agonists (GLP-1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data. MATERIALS AND METHODS: This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC025 regarding the association between GLP-1RA use and suicidality. RESULTS: Although reports of GLP-1RA-associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC -2.77 [IC025 -2.95]). The lack of evidence of an association persisted regardless of whether GLP-1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC -2.95 [IC025 -3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC -1.16 [IC025 -1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP-1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP-1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC025 0.01]). CONCLUSIONS: The suspected association between GLP-1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP-1RA-associated suicidality are likely influenced by factors such as comorbidities present in the GLP-1RA user population.

Psychosocial alterations during the COVID-19 pandemic and the global burden of anxiety and major depressive disorders in adolescents, 1990-2021: challenges in mental health amid socioeconomic disparities.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, a global health crisis, profoundly impacted all aspects of daily life. Adolescence, a pivotal stage of psychological and social development, is heavily influenced by the psychosocial and socio-cultural context. Hence, it is imperative to thoroughly understand the psychosocial changes adolescents experienced during the pandemic and implement effective management initiatives. DATA SOURCES: We examined the incidence rates of depressive and anxiety disorders among adolescents aged 10-19 years globally and regionally. We utilized data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 to compare pre-pandemic (2018-2019) and pandemic (2020-2021) periods. Our investigation covered 204 countries and territories across the six World Health Organization regions. We conducted a comprehensive literature search using databases including PubMed/MEDLINE, Scopus, and Google Scholar, employing search terms such as "psychosocial", "adolescent", "youth", "risk factors", "COVID-19 pandemic", "prevention", and "intervention". RESULTS: During the pandemic, the mental health outcomes of adolescents deteriorated, particularly in terms of depressive and anxiety disorders. According to GBD 2021, the incidence rate of anxiety disorders increased from 720.26 [95% uncertainty intervals (UI) = 548.90-929.19] before the COVID-19 pandemic (2018-2019) to 880.87 per 100,000 people (95% UI = 670.43-1132.58) during the COVID-19 pandemic (2020-2021). Similarly, the incidence rate of major depressive disorder increased from 2333.91 (95% UI = 1626.92-3138.55) before the COVID-19 pandemic to 3030.49 per 100,000 people (95% UI = 2096.73-4077.73) during the COVID-19 pandemic. This worsening was notably pronounced in high-income countries (HICs). Rapid environmental changes, including heightened social anxiety, school closures, economic crises, and exacerbated racism, have been shown to adversely affect the mental well-being of adolescents. CONCLUSIONS: The abrupt shift to remote learning and the absence of in-person social interactions heightened feelings of loneliness, anxiety, sadness, and stress among adolescents. This change magnified existing socioeconomic disparities, posing additional challenges. These complexities profoundly impact adolescents' well-being, especially vulnerable groups like those from HICs, females, and minorities. Acknowledging the underreporting bias in low- to middle-income countries highlights the importance of addressing these mental health alterations in assessments and interventions within these regions as well. Urgent interventions are crucial as the pandemic-induced mental stress may have lasting effects on adolescents' mental health.

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.

Two spurge species, Euphorbia resinifera O. Berg and Euphorbia officinarum subsp. echinus (Hook.f. & Coss.) Vindt inhibit colon cancer.

BACKGROUND: Colon cancer, a prominent contributor to global cancer-related deaths, prompts the need for innovative treatment strategies. Euphorbia resinifera O. Berg (E. resinifera) and Euphorbia officinarum subsp. echinus Hook. f. & Coss Vindt (E. echinus) and their bee-derived products have been integral to traditional Moroccan medicine due to their potential health benefits. These plants have historical use in addressing various health issues, including cancer. However, their effects against colon cancer remain unclear, and the specific mechanisms underlying their anti-cancer effects lack comprehensive investigation. METHODS: The study aimed to assess the potential anti-cancer effects of Euphorbia extract on colon cancer cell lines (DLD-1) through various techniques. The apoptosis, migration, and proliferation of DLD-1 cells were measured in DLD-1 cells. In addition, we conducted High-Performance Liquid Chromatography (HPLC) analysis to identify the profile of phenolic compounds present in the studied extracts. RESULTS: The extracts demonstrated inhibition of colon cancer cell migration. E. resinifera flower and E. echinus stem extracts show significant anti-migratory effects. Regarding anti-proliferative activity, E. resinifera flower extract hindered proliferation, whereas E. echinus flower extract exhibited dose-dependent inhibition. Apoptosis assays revealed E. resinifera flower extract inducing early-stage apoptosis and E. echinus flower extract promoting late-stage apoptosis. While apoptotic protein expression indicated, E. resinifera stem and propolis extracts had minimal impact on apoptosis. CONCLUSION: The findings provide evidence supporting the beneficial effects of E resinifera and E. echinus extracts on colon cancer and exerting anti-cancer properties.

Association of Soda Drinks and Fast Food with Allergic Diseases in Korean Adolescents: A Nationwide Representative Study.

INTRODUCTION: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis). METHODS: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food. RESULTS: Among 865,614 adolescents in grades 7-12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03-1.12) and fast food consumption (1.25; 1.17-1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19-1.44) and fast food (1.46; 1.26-1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks. CONCLUSION: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs.

Global burden of vaccine-associated hepatobiliary and gastrointestinal adverse drug reactions, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.

Comorbid health conditions in people with attention-deficit/hyperactivity disorders: An umbrella review of systematic reviews and meta-analyses.

BACKGROUND: We aimed to systematically review meta-analyses on the link between attention-deficit/hyperactivity disorder (ADHD) and a broad range of psychiatric, physical, and behavioral health conditions (PROSPERO; no.CRD42023448907). RESULTS: We identified 22 meta-analyses that included 544 primary studies, covering 76 unique conditions in over 234 million participants across 36 countries and six continents. We found high-certainty evidence for the associations between ADHD and neuropsychiatric conditions (bipolar disorders, personality disorders, schizophrenia, and pragmatic language skills), night awakenings, obesity, decayed incipient surfaces, asthma, astigmatism, hyperopia and hypermetropia, strabismus, and suicide ideation. Moderate-certainty evidence suggested that ADHD was associated with headache, mood/affective disorders, depression, bruxism, bone fractures, atopic rhinitis, vision problems, suicide attempts, completed suicide, and all-cause mortality. Low-certainty evidence indicated associations with eating disorders, sleep efficiency, type 2 diabetes, dental trauma prevalence, atopic diseases, and atopic dermatitis. Very low-certainty evidence showed associations between ADHD and several sleep parameters. CONCLUSION: We found varied levels of evidence for the associations of ADHD with multiple health conditions. Therefore, clinicians should consider a wide range of neurological, psychiatric, sleep and suicide-related, metabolic, musculoskeletal, oral, allergic, and visual conditions, as well as the increased risk of mortality when assessing individuals with ADHD.

Global public concern of childhood and adolescence suicide: a new perspective and new strategies for suicide prevention in the post-pandemic era.

BACKGROUND: Suicide is the second leading cause of death in young people worldwide and is responsible for about 52,000 deaths annually in children and adolescents aged 5-19 years. Familial, social, psychological, and behavioral factors play important roles in suicide risk. As traumatic events such as the COVID-19 pandemic may contribute to suicidal behaviors in young people, there is a need to understand the current status of suicide in adolescents, including its epidemiology, associated factors, the influence of the pandemic, and management initiatives. DATA SOURCES: We investigated global and regional suicide mortality rates among children and adolescents aged 5-19 years using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The suicide mortality rates from 1990 to 2019 were examined in 204 countries and territories across six World Health Organization (WHO) regions. Additionally, we utilized electronic databases, including PubMed/MEDLINE and Scopus, and employed various combinations of terms such as "suicide", "adolescents", "youth", "children", "risk factors", "COVID-19 pandemic", "prevention", and "intervention" to provide a narrative review on suicide within the pediatric population in the post-pandemic era. RESULTS: Despite the decreasing trend in the global suicide mortality rate from 1990 to 2019, it remains high. The mortality rates from suicide by firearms or any other specified means were both greater in males. Additionally, Southeast Asia had the highest suicide rate among the six WHO regions. The COVID-19 pandemic seems to contribute to suicide risk in young people; thus, there is still a strong need to revisit appropriate management for suicidal children and adolescents during the pandemic. CONCLUSIONS: The current narrative review integrates up-to-date knowledge on suicide epidemiology and the effects of the COVID-19 pandemic, risk factors, and intervention strategies. Although numerous studies have characterized trends in suicide among young people during the pre-pandemic era, further studies are required to investigate suicide during the pandemic and new strategies for suicide prevention in the post-pandemic era. It is necessary to identify effective prevention strategies targeting young people, particularly those at high risk, and successful treatment for individuals already manifesting suicidal behaviors. Care for suicidal children and adolescents should be improved with parental, school, community, and clinical involvement.

Biomarkers and Related Factors for the Diagnosis, Risk of Coronary Artery Lesions, and Resistance to Intravenous Immunoglobulin in Kawasaki Disease: An Umbrella Review of Meta-Analyses.

Kawasaki disease (KD) is a self-limited febrile disease predominantly affecting infants and children under 5 years old. Coronary artery lesions (CAL) are a prevalent complication, highlighting the necessity for swift diagnosis and treatment. A comprehensive review of biomarkers applicable for the diagnosis and treatment of Kawasaki disease (KD) in clinical settings is imperative. To provide a comprehensive review and analysis of biomarkers for diagnosis of KD, incidence of CAL, and intravenous immunoglobulin (IVIG) resistance. The data included in our study were sourced from searches conducted in PubMed/MEDLINE, Embase, EBSCO, and Google Scholar until March 15, 2024. Studies investigating the association with KD or evaluating diagnostic value were included in our study. Eligibility was independently assessed by two authors, with conflicts resolved through discussion. Data extraction was performed by 2 independent authors, following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline. Data were pooled using a random-effects model. We assess biomarkers relevant to KD, categorizing them into three groups: diagnostic, associated with CAL incidence, and linked to IVIG resistance. For studies focusing solely on association, we present standardized mean differences (SMD). For those reporting sensitivity and specificity as diagnostic measures, we calculate the diagnostic odds ratio (DOR) to compare their efficacy. We identified 14 meta-analyses on biomarkers related to KD. 11 biomarkers exhibited diagnostic value for KD, while 21 were associated with its progression. Four biomarkers, including non-coding RNAs (DOR, 19.35 [95% CI, 13.58-27.56]), Serum ferritin (DOR, 24.90 [11.67-53.12]), N terminal proBNP (DOR, 21.03 [9.03-49.00]), and micro RNAs (DOR, 45.28 [6.30-325.52]), have significant diagnostic value for the diagnosis of KD. Seven biomarkers showed significant association with the incidence of CAL. Twenty biomarkers were for the prediction of IVIG resistance, including prognostic nutritional index (DOR, 7.72 [95% CI, 2.37-25.09]), non-coding RNAs (DOR, 14.63 [3.24-66.14]), neutrophil to lymphocyte ratio (DOR, 6.62 [4.05-10.81]), platelet to lymphocyte ratio (DOR, 3.30 [2.10-5.19]), and C reactive protein (DOR, 6.58 [3.69-11.74]). Based on the evidence, we have proposed various biomarkers associated with KD. Our aim is for these biomarkers to have wide applicability in both diagnostic and therapeutic settings.

Global association of secondhand smoke exposure locations and smoking behaviour among adolescents in 99 countries.

AIM: This study classified 99 countries into four income groups and then analysed the impact of secondhand smoke (SHS) exposure at home, in public places and at school, on current cigarette smoking prevalence. METHODS: We utilised data from the WHO Global Youth Tobacco Survey and a meta-analysis was conducted to evaluate the prevalence and weighted odds ratios (wORs) of adolescent smoking behaviour and SHS exposure locations. RESULTS: Both smoking behaviours increased with higher national income levels. Smoking behaviours in high and upper-middle-income countries (HICs and UMICs) exhibited an association with SHS exposure in public places (HIC: wOR, 3.50 [95% CI, 2.85-4.31]; UMIC: wOR, 2.90 [2.60-3.23]) compared to home. Low- and lower-middle-income countries (LICs and LMICs) showed an association with SHS exposure in the home (LIC: wOR, 5.33 [3.59-7.93]; LMIC: wOR, 2.71 [2.33-3.17]) than public places. The association between current cigarette smoking and SHS exposure at home increased with lower income levels, while anticipated future use of any form of tobacco with SHS exposure in public places rose in lower income countries. CONCLUSIONS: Targeted interventions based on income levels are essential, emphasising home strategies in lower income countries and public place efforts in higher income countries.

Global and regional burden of vaccine-induced thrombotic thrombocytopenia, 1969-2023: Comprehensive findings with critical analysis of the international pharmacovigilance database.

OBJECTIVE: The scarcity of studies on vaccine-induced thrombosis and thrombocytopenia syndrome (TTS) limits the comprehensive understanding of vaccine safety on a global scale. Therefore, the objective of this study is to assess the global burden of vaccine-induced TTS, identify the vaccines most associated with it, and suggest clinical implications regarding vaccination. METHODS: This study employed the World Health Organization international pharmacovigilance database, extracting records of vaccine-induced immune thrombotic thrombocytopenia from 1969 to 2023 (total reports, n > 130 million). Global reporting counts, reported odds ratios (ROR), and information components (IC) were calculated to identify the association between 19 vaccines and the occurrence of vaccine-induced TTS across 156 countries. RESULTS: We identified 24 233 cases (male, n = 11 559 [47.7%]) of vaccine-induced TTS among 404 388 reports of all-cause TTS. There has been a significant increase in reports of vaccine-induced TTS events over time, with a noteworthy surge observed after 2020, attributed to cases of TTS associated with COVID-19 vaccines. Measles, mumps, and rubella (MMR) vaccines were associated with most TTS reports (ROR [95% confidence interval], 2.87 [2.75-3.00]; IC [IC0.25], 1.51 [1.43]), followed by hepatitis B (HBV, 2.23 [2.07-2.39]; 1.15 [1.03]), rotavirus diarrhea (1.95 [1.78-2.13]; 0.81 [0.53]), encephalitis (1.80 [1.50-2.16]; 0.84 [0.53]), hepatitis A (1.67 [1.50-1.86]; 0.73 [0.55]), adenovirus Type 5 vector-based (Ad5-vectored) COVID-19 (1.64 [1.59-1.68]; 0.69 [0.64]), pneumococcal (1.57 [1.49-1.66]; 0.65 [0.56]), and typhoid vaccines (1.41 [1.12-1.78]; 0.49 [0.11]). Concerning age and sex-specific risks, reports of vaccine-induced TTS were more associated with females and younger age groups. The age group between 12 and 17 years exhibited significant sex disproportion. Most of these adverse events had a short time to onset (days; mean [SD], 4.99 [40.30]) and the fatality rate was 2.20%, the highest rate observed in the age group over 65 years (3.79%) and lowest in the age group between 0 and 11 years (0.31%). CONCLUSION: A rise in vaccine-induced TTS reports, notably MMR, HBV, and rotavirus diarrhea vaccines, was particularly related to young females. Ad5-vectored COVID-19 vaccines showed comparable or lower association with TTS compared to other vaccines. Despite the rarity of these adverse events, vigilance is essential as rare complications can be fatal, especially in older groups. Further studies with validated reporting are imperative to improve the accuracy of assessing the vaccine-induced TTS for preventive interventions and early diagnosis.

Global and regional burden of vaccine-associated facial paralysis, 1967-2023: Findings from the WHO international pharmacovigilance database.

The scarce and conflicting data on vaccine-associated facial paralysis limit our understanding of vaccine safety on a global scale. Therefore, this study aims to evaluate the global burden of vaccine-associated facial paralysis and to identify the extent of its association with individual vaccines, thereby contributing to the development of a more effective vaccination program. We used data on vaccine-associated facial paralysis from 1967 to 2023 (total reports, n = 131 255 418 418) from the World Health Organization International Pharmacovigilance Database. Global reporting counts, reported odds ratios (ROR), and information components (ICs) were computed to elucidate the association between the 16 vaccines and the occurrence of vaccine-associated facial paralysis across 156 countries. We identified 26 197 reports (men, n = 10 507 [40.11%]) of vaccine-associated facial paralysis from 49 537 reports of all-cause facial paralysis. Vaccine-associated facial paralysis has been consistently reported; however, a pronounced increase in reported incidence has emerged after the onset of the coronavirus disease 2019 (COVID-19) pandemic, which is attributable to the COVID-19 mRNA vaccine. Most vaccines were associated with facial paralysis, with differing levels of association, except for tuberculosis vaccines. COVID-19 mRNA vaccines had the highest association with facial paralysis reports (ROR, 28.31 [95% confidence interval, 27.60-29.03]; IC, 3.37 [IC0.25, 3.35]), followed by encephalitis, influenza, hepatitis A, papillomavirus, hepatitis B, typhoid, varicella-zoster, meningococcal, Ad-5 vectored COVID-19, measles, mumps and rubella, diphtheria, tetanus toxoids, pertussis, polio, and Hemophilus influenza type b, pneumococcal, rotavirus diarrhea, and inactivated whole-virus COVID-19 vaccines. Concerning age- and sex-specific risks, vaccine-associated facial paralysis was more strongly associated with older age groups and males. The serious adverse outcome and death rate of vaccine-associated facial paralysis were extremely low (0.07% and 0.00%, respectively). An increase in vaccine-induced facial paralysis, primarily owing to COVID-19 mRNA vaccines, was observed with most vaccines, except tuberculosis vaccines. Given the higher association observed in the older and male groups with vaccine-associated facial paralysis, close monitoring of these demographics when administering vaccines that are significantly associated with adverse reactions is crucial.

Facile Synthesis of Nitrogen-Doped Graphene Quantum Dots/MnCO3/ZnMn2O4 on Ni Foam Composites for High-Performance Supercapacitor Electrodes.

This study reports the facile synthesis of rationally designed composite materials consisting of nitrogen-doped graphene quantum dots (N-GQDs) and MnCO3/ZnMn2O4 (N/MC/ZM) on Ni foam using a simple hydrothermal method to produce high-performance supercapacitor applications. The N/MC/ZM composite was uniformly synthesized on a Ni foam surface with the hierarchical structure of microparticles and nanosheets, and the uniform deposition of N-GQDs on a MC/ZM surface was observed. The incorporation of N-GQDs with MC/ZM provides good conductivity, charge transfer, and electrolyte diffusion for a better electrochemical performance. The N/MC/ZM composite electrode delivered a high specific capacitance of 960.6 F·g-1 at 1 A·g-1, low internal resistance, and remarkable cycling stability over 10,000 charge-discharge cycles. Additionally, an all-flexible solid-state asymmetric supercapacitor (ASC) device was fabricated using the N/MC/ZM composite electrode. The fabricated ASC device produced a maximum energy density of 58.4 Wh·kg-1 at a power density of 800 W·kg-1 and showed a stable capacitive performance while being bent, with good mechanical stability. These results provide a promising and effective strategy for developing supercapacitor electrodes with a high areal capacitance and high energy density.

Protective effect of the mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt extract on respiratory disorders.

Air pollutants, such as particulate matter (PM) and diesel exhaust particles (DEP), are associated with respiratory diseases. Therefore, preventive and therapeutic strategies against PM-and DEP (PM10D)-induced respiratory diseases are needed. Herein, we evaluate the protective effects of a mixture of Lactiplantibacillus plantarum KC3 and Leonurus Japonicas Houtt (LJH) extract against airway inflammation associated with exposure to PM10D. To determine the anti-inflammatory effects of the LJH extract, reactive oxygen species (ROS) production and the expression of inflammatory pathways were determined in PM10-induced MH-S cells. For the respiratory protective effects, BALB/c mice were exposed to PM10D via intranasal injection, and a mixture of L. plantarum KC3 and LJH extract was administered orally for 12 days. LJH extract inhibited ROS production and the phosphorylation of downstream factors of NF-κB in PM10-stimulated MH-S cells. The mixture of L. plantarum KC3 and LJH repressed the infiltration of neutrophils, reduced the immune cells number, and suppressed the proinflammatory mediators and cyclooxygenase (COX)-2 expressions in PM10D-induced airway inflammation with reduced phosphorylation of downstream factors of NF-κB. In addition, these effects were not observed in an alveolar macrophage depleted PM10D-induced mouse model using clodronate liposomes. The extract mixture also regulated gut microbiota in feces and upregulated the mRNA expression of Foxp3, transforming growth factor (TGF)-ß1, and interleukin (IL)-10 in the colon. The L. plantarum KC3 and LJH extract mixture may inhibit alveolar macrophage- and neutrophil-mediated inflammatory responses and regulate gut microbiota and immune response in PM10D-induced airway inflammation, suggesting it is a potential remedy to prevent and cure airway inflammation and respiratory disorders.

National and regional trends in the prevalence of type 2 diabetes and associated risk factors among Korean adults, 2009-2021.

Disproportionate impact of COVID-19 on socioeconomic and behavioral variables may have impacted the prevalence of diabetes. We utilized nationwide long-term serial study from the 2009 to 2021 Korea Community Health Survey (KCHS). We explored national and regional prevalence and trends of diabetes according to the socioeconomic and behavioral factors before and during the pandemic. Also, we interpreted which groups became more vulnerable to the prevalence of diagnosed diabetes during the pandemic. A total of 2,971,349 adults aged (19 to 39, 40 to 59, and ≥ 60 years) were included in the analysis. The prevalence of diagnosed diabetes increased slowly during the pandemic (11.6% [95% CI 11.5-11.7] in 2020 and 12.4% [95% CI 12.3-12.6] in 2021), compared to the pre-pandemic era (7.9% [95% CI 7.8-7.9] in 2009-2011 and 11.3% [95% CI 11.3-11.4] in 2018-2019). Also, women, low-income group, low-educational group, and infrequent walking group showed less prevalence of diagnosed diabetes than the others. The diabetic population increased slowly than expected during the pandemic. The pandemic seems to contribute to an unanticipated increase in under-diagnosis of diabetes among the already minority. This study may suggest reinforcing access to healthcare services among the minority during the pandemic.

2-Geranyl-1-methoxyerythrabyssin II alleviates lipid accumulation and inflammation in hepatocytes through AMPK activation and AKT inhibition.

A growing proportion of the global adult and pediatric populations are currently affected by nonalcoholic steatohepatitis (NASH), leading to rising rates of liver fibrosis and hepatocellular carcinoma without effective pharmacotherapy. Here, we investigated whether 2-geranyl-1-methoxyerythrabyssin II (GMET), isolated from Lespedeza bicolor, could alleviate lipid accumulation and inflammatory responses in a NASH model. GMET exhibited potent in vitro and in vivo effects against lipid accumulation and attenuated inflammatory responses without cytotoxicity. Mechanistically, GMET inhibits acetyl-CoA carboxylase (ACC), sterol regulatory element-binding proteins-1c (SREBP1), and mammalian target of rapamycin (mTOR), and activates PPARα by activating AMP-activated kinase (AMPK), leading to the alleviation of lipid accumulation. In addition, GMET suppresses the NF-κB pathway by activating AMPK and inhibiting the activated protein kinase B (AKT)/IκB-kinase (IKK) pathway, leading to the inhibition of the inflammatory response in hepatocytes. All these protective effects of GMET on lipid accumulation and inflammation in vivo and in vitro were largely abolished by co-treatment with dorsomorphin, an AMPK inhibitor. In conclusion, GMET alleviated lipid accumulation and inflammation to preserve normal hepatocyte function in steatohepatitis. Thus, GMET is a novel potential multi-targeting compound to improve steatohepatitis.

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.