Global burden of vaccine-associated multiple sclerosis, 1967–2022: a comprehensive analysis of the international pharmacovigilance database

Vaccine-associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large-scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine-associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine-associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine-associated MS across 156 countries and territories. We identified 8288 reports of vaccine-associated MS among 132 980 cases of all-cause MS. The cumulative number of reports on vaccine-associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID-19 mRNA vaccine-associated MS. Vaccine-associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC025 4.18), followed by encephalitis (ROR 7.42; IC025 2.59), hepatitis A (ROR 4.46; IC025 1.95), and papillomavirus vaccines (ROR 4.45; IC025 2.01). Additionally, MS showed a significantly disproportionate signal for COVID-19 mRNA vaccines (ROR 1.55; IC025 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine-associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID-19 mRNA vaccines, and should consider the risk factors associated with vaccine-associated MS.</p

Global burden of vaccine-associated multiple sclerosis, 1967–2022: a comprehensive analysis of the international pharmacovigilance database

Vaccine-associated multiple sclerosis (MS) is rare, with insufficient evidence from case reports. Given the scarcity of large-scale data investigating the association between vaccine administration and adverse events, we investigated the global burden of vaccine-associated MS and potential related vaccines from 1967 to 2022. Reports on vaccine-associated MS between 1967 and 2022 were obtained from the World Health Organization International Pharmacovigilance Database (total number of reports = 120 715 116). We evaluated global reports, reporting odds ratio (ROR), and information components (IC) to investigate associations between 19 vaccines and vaccine-associated MS across 156 countries and territories. We identified 8288 reports of vaccine-associated MS among 132 980 cases of all-cause MS. The cumulative number of reports on vaccine-associated MS gradually increased over time, with a substantial increase after 2020, owing to COVID-19 mRNA vaccine-associated MS. Vaccine-associated MS develops more frequently in males and adolescents. Nine vaccines were significantly associated with higher MS reporting, and the highest disproportional associations were observed for hepatitis B vaccines (ROR 19.82; IC025 4.18), followed by encephalitis (ROR 7.42; IC025 2.59), hepatitis A (ROR 4.46; IC025 1.95), and papillomavirus vaccines (ROR 4.45; IC025 2.01). Additionally, MS showed a significantly disproportionate signal for COVID-19 mRNA vaccines (ROR 1.55; IC025 0.52). Fatal clinical outcomes were reported in only 0.3% (21/8288) of all cases of vaccine-associated MS. Although various vaccines are potentially associated with increased risk of MS, we should be cautious about the increased risk of MS following vaccination, particularly hepatitis B and COVID-19 mRNA vaccines, and should consider the risk factors associated with vaccine-associated MS.</p

Prediction Model for Cardiovascular Disease in Patients with Diabetes Using Machine Learning Derived and Validated in Two Independent Korean Cohorts

This study aimed to develop and validate a machine learning (ML) model tailored to the Korean population with type 2 diabetes mellitus (T2DM) to provide a superior method for predicting the development of cardiovascular disease (CVD), a major chronic complication in these patients. We used data from two cohorts, namely the discovery (one hospital; n = 12,809) and validation (two hospitals; n = 2019) cohorts, recruited between 2008 and 2022. The outcome of interest was the presence or absence of CVD at 3 years. We selected various ML-based models with hyperparameter tuning in the discovery cohort and performed area under the receiver operating characteristic curve (AUROC) analysis in the validation cohort. CVD was observed in 1238 (10.2%) patients in the discovery cohort. The random forest (RF) model exhibited the best overall performance among the models, with an AUROC of 0.830 (95% confidence interval [CI] 0.818–0.842) in the discovery dataset and 0.722 (95% CI 0.660–0.783) in the validation dataset. Creatinine and glycated hemoglobin levels were the most influential factors in the RF model. This study introduces a pioneering ML-based model for predicting CVD in Korean patients with T2DM, outperforming existing prediction tools and providing a groundbreaking approach for early personalized preventive medicine. </p

National and regional trends in the prevalence of hypertension in South Korea amid the pandemic, 2009–2022: a nationwide study of over 3 million individuals

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Prenatal and infant exposure to antibiotics and subsequent risk of neuropsychiatric disorders in children: a nationwide birth cohort study in South Korea

We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study (infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05–1.08]) and postnatal life (1.05 [1.03–1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09–1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05–1.08]) and severe outcomes (1.17 [1.09–1.26]), especially for intellectual disability (1.12 [1.07–1.17]), ADHD (1.10 [1.07–1.13]), anxiety (1.06 [1.02–1.11]), mood (1.06 [1.00–1.12]), and autism (1.03 [1.01–1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6–12) and 12 % (7–17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription. </p

Differences in Pandemic-Related Factors Associated with Alcohol and Substance Use among Korean Adolescents: Nationwide Representative Study

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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. </p

Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis

On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre‐outbreak (2003–2021) and the current mpox outbreak. In this systematic review and meta‐analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword “monkeypox” and “mpox” up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52–17.08), fever (0.68, 0.49–0.94), pruritus (0.25, 0.19–0.32), myalgia (0.50, 0.31–0.81), headache (0.56, 0.35–0.88), skin ulcer (0.32, 0.17–0.59), abdominal symptom (0.29, 0.20–0.42), pharyngitis (0.32, 0.18–0.58), nausea or vomiting (0.15, 0.02–0.93), conjunctivitis (0.11, 0.03–0.38), concomitant infection with HIV (1.70, 0.95–3 0.04), and death (0.02, 0.001–0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox‐related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.</p

National Trends in Sadness, Suicidality, and COVID-19 Pandemic–Related Risk Factors Among South Korean Adolescents From 2005 to 2021

Importance Despite the COVID-19 pandemic’s effect on daily life, limited research exists on the prevalence and risk factors of suicidality and sadness among South Korean adolescents. Objectives To examine whether the observed sadness and suicidality in the early to middle periods of the COVID-19 pandemic differed from the expected level and to investigate changes in risk factors for sadness and suicidality. Design, Setting, and Participants This nationwide serial cross-sectional survey study used data on 1 109 776 Korean adolescents aged 13 to 18 years from the Korea Youth Risk Behavior Web-based Survey from 2005 to 2021. Exposure The COVID-19 pandemic. Main Outcomes and Measures The pattern of changes in the percentage or proportion of sadness or suicidality, as well as the risk factors for sadness or suicidality. The transitional effect of the COVID-19 pandemic was assessed using weighted odds ratios (wORs) or weighted beta coefficients with 95% CIs. Results Between 2005 and 2021, 1 109 776 adolescents (mean [SD] age, 15.0 [1.7] years; 51.5% male adolescents; and 51.7% in grades 7-9 and 48.3% in grades 10-12) were included in the Korea Youth Risk Behavior Web-based Survey. The slope of the long-term trends in sadness and suicidality decreased in the prepandemic period (sadness: from 37.8% [95% CI, 37.4%-38.2%] in 2005-2007 to 26.1% [95% CI, 25.9%-26.4%] in 2016-2019; suicidality: from 23.0% [95% CI, 22.7%-23.3%] in 2005-2007 to 12.3% [95% CI, 12.1%-12.5%] in 2016-2019), whereas the slope increased during the COVID-19 pandemic (sadness: from 25.0% [95% CI, 24.5%-25.6%] in 2020 to 26.6% [95% CI, 26.1%-27.1%] in 2021; trend difference in β, 0.249 [95% CI, 0.236-0.262]; suicidality: from 10.7% [95% CI, 10.3%-11.1%] in 2020 to 12.5% [95% CI, 12.1%-12.9%] in 2021; trend difference in β, 0.328 [95% CI, 0.312-0.344]). The trends presented a similar tendency in the subgroups according to sex, school grade, residential area, smoking status, and current alcohol use. Compared with the prepandemic period, the risk factors associated with sadness during the pandemic were younger age (wOR, 0.907; 95% CI, 0.881-0.933), female sex (wOR, 1.031; 95% CI, 1.001-1.062), urban residence (wOR, 1.120; 95% CI, 1.087-1.153), current smoking status (wOR, 1.134; 95% CI, 1.059-1.216), and current alcohol use (wOR, 1.051; 95% CI, 1.002-1.102). Female sex (wOR, 1.064; 95% CI, 1.021-1.109), urban residence (wOR, 1.117; 95% CI, 1.074-1.162), and low economic status (wOR, 1.286; 95% CI, 1.180-1.403) were the risk factors significantly associated with suicidality after the COVID-19 pandemic began. Conclusions and Relevance In this nationwide serial cross-sectional survey study of South Korean adolescents, the slope of the prevalence of sadness and suicidality increased during the COVID-19 pandemic after a decrease prior to the pandemic. The findings suggest that public health measures are needed to recognize vulnerable groups with risk factors and to prevent an increase in sadness and suicidality among adolescents during the COVID-19 pandemic

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.</p