Severe mental illness and mortality in sepsis and septic shock: a systematic review and meta-analysis.

BACKGROUND: There have been conflicting reports regarding the case-fatality outcomes associated with sepsis and septic shock in patients with severe mental illness (SMI). METHODS: We searched Medline®, Web of Science® and the Cochrane Library® databases (from inception to 4-July-2023) for papers reporting outcomes associated with sepsis and septic shock in adult with (cases) vs. without SMI (controls). The main study outcome was the unadjusted case-fatality rate at hospital discharge, or 30 days if unavailable. Secondary outcomes included the rates of adjusted case-fatality at hospital discharge. RESULTS: A total of six studies were included in the systematic review, of which four provided data for meta-analysis involving 2,124,072 patients. Compared to controls, patients with SMI were younger and more frequently women. Unadjusted analyses showed that SMI patients had a lower case-fatality rate associated with sepsis and septic shock than their non-SMI counterparts (OR 0.61, 95% CI [0.58-0.65], PI 95% CI [0.49-0.77], I2 = 91%). Meta-regression and subgroup analyses showed that the denominator of the study population (i.e. septic shock or sepsis) was associated with the outcome with an R2 of 59.7%. CONCLUSION: In conclusion, our study reveals a survival advantage of SMI patients over their non-SMI counterparts. Further research is needed to fully elucidate the mechanisms involved and to develop targeted interventions that can improve the prognosis of both SMI and non-SMI patients facing sepsis.

Comorbid health outcomes in patients with schizophrenia: an umbrella review of systematic reviews and meta-analyses.

There is no comprehensive umbrella review exploring the connection between schizophrenia and various health outcomes. Therefore, we aimed to systematically review existing meta-analyses about schizophrenia-associated comorbid health outcomes and validate the evidence levels. We performed an umbrella review of meta-analyses of observational studies to explore comorbid health outcomes in individuals with schizophrenia. Searches were conducted across PubMed/MEDLINE, EMBASE, ClinicalKey, and Google Scholar up to September 5, 2023, targeting meta-analyses of observational studies related to comorbid health outcomes in individuals with schizophrenia. We applied AMSTAR2 for data extraction and quality assessment, adhering to PRISMA guidelines. Evidence credibility was evaluated and categorized by evidence quality. Our protocol was registered with PROSPERO (CRD42024498833). Risk and protective factors were analyzed and presented through equivalent odds ratios (eRR). In this umbrella review, we analyzed 9 meta-analyses, including 88 original articles, covering 21 comorbid health outcomes with over 66 million participants across 19 countries. Patients with schizophrenia showed significant associations with multiple health outcomes, including asthma (eRR, 1.71 [95% CI, 1.05-2.78], class and quality of evidence [CE] = non-significant), chronic obstructive pulmonary disease (1.73 [1.25-2.37], CE = weak), pneumonia (2.63 [1.11-6.23], CE = weak), breast cancer of female patients (1.31 [1.04-1.65], CE = weak), cardiovascular disease (1.53 [1.12-2.11], CE = weak), stroke (1.71 [1.30-2.25], CE = weak), congestive heart failure (1.81 [1.21-2.69], CE = weak), sexual dysfunction (2.30 [1.75-3.04], CE = weak), fracture (1.63 [1.10-2.40], CE = weak), dementia (2.29 [1.19-4.39], CE = weak), and psoriasis (1.83 [1.18-2.83] CE = weak). Our study underscores the imperative for an integrated treatment approach to schizophrenia, highlighting its broad impact across respiratory, cardiovascular, sexual, neurological, and dermatological health domains. Given the predominantly non-significant to weak evidence levels, further studies are needed to reinforce our understanding.

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.

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.

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.

Roles of SMAD and SMAD-Associated Signaling Pathways in Nerve Regeneration Following Peripheral Nerve Injury: A Narrative Literature Review.

Although several methods are being applied to treat peripheral nerve injury, a perfect treatment that leads to full functional recovery has not yet been developed. SMAD (Suppressor of Mothers Against Decapentaplegic Homolog) plays a crucial role in nerve regeneration by facilitating the survival and growth of nerve cells following peripheral nerve injury. We conducted a systematic literature review on the role of SMAD in this context. Following peripheral nerve injury, there was an increase in the expression of SMAD1, -2, -4, -5, and -8, while SMAD5, -6, and -7 showed no significant changes; SMAD8 expression was decreased. Specifically, SMAD1 and SMAD4 were found to promote nerve regeneration, whereas SMAD2 and SMAD6 inhibited it. SMAD exerts its effects by promoting neuronal survival and growth through BMP/SMAD1, BMP/SMAD4, and BMP/SMAD7 signaling pathways. Furthermore, it activates nerve regeneration programs via the PI3K/GSK3/SMAD1 pathway, facilitating active regeneration of nerve cells and subsequent functional recovery after peripheral nerve damage. By leveraging these mechanisms of SMAD, novel strategies for treating peripheral nerve damage could potentially be developed. We aim to further elucidate the precise mechanisms of nerve regeneration mediated by SMAD and explore the potential for developing targeted nerve treatments based on these findings.

Risks of alopecia areata in long COVID: Binational population-based cohort studies from South Korea and Japan.

Previous studies have proposed alopecia areata (AA) as a potential outcome of COVID-19 infection among autoimmune diseases, yet the findings might be inconclusive and difficult to generalize due to limited sample sizes and evidence levels. Thus, we aimed to investigate in detail the long-term risk of AA following SARS-CoV-2 infection based on large, binational, general population-based cohort studies. Our study investigated the long-term AA risk after SARS-CoV-2 infection by analyzing bi-national, claim-based cohorts in South Korea and Japan: a Korean nationwide cohort (K-COV-N cohort; discovery cohort; total n = 10 027 506) and a Japanese claims-based cohort (JMDC cohort; validation cohort; total n = 12 218 680). AA was identified based on the international classification of diseases 10th revision code (L63) requiring at least three claims within 1 year. After exposure-driven propensity score matching, SARS-CoV-2 infection was associated with an increased risk of incident AA (aHR, 1.66; 95% CI, 1.38-1.99). This increased risk was observed and persisted for up to 6 months. A similar pattern was observed in the validation cohort. As modifiable factors, severe COVID-19 increased the risk of AA, whereas receiving two or more doses of the COVID-19 vaccine before infection decreased the risk of AA. Through a bi-national cohort study in South Korea and Japan, SARS-CoV-2 infection was associated with an elevated risk for incident AA in the aspect of long COVID.

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.

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.

Global estimates on the reports of vaccine-associated myocarditis and pericarditis from 1969 to 2023: Findings with critical reanalysis from the WHO pharmacovigilance database.

Due to the limitation of previous studies examining adverse reports of myocarditis and pericarditis associated with vaccines other than the COVID-19 vaccine, there are challenges in establishing a comprehensive understanding of vaccine safety on a global scale. Hence, the objective of this study was to examine the worldwide burden of vaccine-associated pericarditis and myocarditis and the vaccines associated with these indications. This study utilized the World Health Organization international pharmacovigilance database, from which records of vaccine-associated pericarditis and myocarditis between 1969 and 2023 were extracted (over 130 million reports). We calculated global reporting counts, reported odds ratios (RORs), and information components (ICs) to discern the association between 19 vaccines and the occurrence of pericarditis and myocarditis across 156 countries and territories. We identified 49 096 reports (male, n = 30 013) of vaccine-associated pericarditis and myocarditis among 73 590 reports of all-cause pericarditis and myocarditis. There has been a significant increase in reports of vaccine-related cardiac adverse events over time, with a noteworthy surge observed after 2020, attributed to cases of pericarditis associated with COVID-19 mRNA vaccines. Smallpox vaccines were associated with most pericarditis and myocarditis reports (ROR: 73.68 [95% CI, 67.79-80.10]; IC [IC0.25]: 6.05 [5.91]), followed by COVID-19 mRNA vaccine (37.77 [37.00-38.56]; 3.07 [3.05]), anthrax vaccine (25.54 [22.37-29.16]; 4.58 [4.35]), typhoid vaccine (6.17 [5.16-7.38]; 2.59 [2.29]), encephalitis vaccine (2.00 [1.48-2.71]; 0.99 [0.47]), influenza vaccine (1.87 [1.71-2.04]; 0.90 [0.75]), and Ad5-vectored COVID-19 vaccine (1.40 [1.34-1.46]; 0.46 [0.39]). Concerning age and sex-specific risks, reports of vaccine-associated pericarditis and myocarditis were more prevalent among males and in older 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 (median time: 1 day) and fatality rate was 0.44%. Our analysis of global data revealed an increase in pericarditis and myocarditis reports associated with vaccines, particularly live vaccines like smallpox and anthrax, notably in young males. While these adverse events are generally rare and mild, caution is warranted, especially for healthcare workers, due to potential myocardial injury-related in-hospital mortality. Further study with validated reporting is crucial to enhance accuracy in evaluating the correlation between vaccines and cardiac conditions for preventive measures.

Risks of cutaneous immune-related adverse events in long COVID: Multinational cohort studies in South Korea, Japan, and the UK.

Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management.

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.

Cardiovascular and Cerebrovascular Adverse Events Associated with Intravitreal Anti-VEGF Monoclonal Antibodies: A World Health Organization Pharmacovigilance Study.

PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-VEGF (aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. PARTICIPANTS: VigiBase, a World Health Organization (WHO) global safety report database. DESIGN: Pharmacovigilance study. METHODS: The individual case safety reports (ICSRs) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, there were 23 129 ADRs after intravitreal anti-VEGF therapy and 25 015 132 ADRs associated with any drug (full database). MAIN OUTCOME MEASURES: The reporting odds ratio (ROR) and information components (ICs) were calculated, and the 95% lower credibility interval end point of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odds ratio (rOR). RESULTS: Compared with the full database, anti-VEGFs were associated with an increased reporting of myocardial infarction (IC025 0.75; ROR: 1.78 [95% CI, 1.70-1.86]), angina pectoris (IC025 0.53; ROR: 1.61 [95% CI, 1.47-1.77]), arrhythmias including atrial fibrillation, atrial flutter, ventricular fibrillation, supraventricular tachycardia (all IC025 > 0,.ROR>1), hypertension (IC025 2.22; ROR: 4.91 [95% CI, 4.82-5.01]), and hypertensive crisis (IC025 1.97; ROR: 4.49 [95% CI, 4.07-4.97]). Moreover, anti-VEGFs were associated with a higher reporting of cerebrovascular ADRs such as cerebral infarction (IC025 4.34; ROR: 23.19 [95% CI, 22.10-24.34]), carotid artery stenosis (IC025 1.85; ROR: 5.24 [95% CI, 3.98-6.89]), cerebral hemorrhage (IC025 2.29; ROR: 5.38 [95% CI, 5.03-5.76]), and subarachnoid hemorrhage (IC025 1.98; ROR: 4.81 [95% CI, 4.14-5.6]). Inter-drug comparison indicated that compared with ranibizumab, patients receiving aflibercept showed overall under-reporting of cardiovascular and cerebrovascular ADRs such as myocardial infarction (rOR 0.55 [95% CI, 0.49-0.52]), atrial fibrillation (rOR 0.28 [95% CI, 0.23-0.35]), cerebrovascular accident (rOR, 0.15 [95% CI, 0.14-0.17]), and cerebral hemorrhage (rOR, 0.51 [95% CI, 0.40-0.65]). CONCLUSIONS: In this pharmacovigilance case-noncase study, there was significantly increased reporting of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment. Although ranibizumab may exhibit superior systemic safety regarding its biological characteristics, it is crucial not to overlook the occurrence of cardiovascular and cerebrovascular ADRs considering its higher reporting rate than bevacizumab or aflibercept. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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

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

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

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

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

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

Sex-Specific and Long-Term Trends of Asthma, Allergic Rhinitis, and Atopic Dermatitis in South Korea, 2007-2022: A Nationwide Representative Study.

INTRODUCTION: Although sex differences in allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and asthma are considered important, a limited number of studies during the COVID-19 pandemic investigated this aspect. Therefore, this study aimed to analyze sex-specific and long-term trends and risk factors for allergic diseases before and during the pandemic. METHODS: This study utilized data from the Korea National Health and Nutrition Examination Survey, 2007-2022, including 92,135 participants aged 19 years and older. This study used weighted multivariate regression analysis to examine the estimates of related factors and assessed weighted odds ratios or ß-coefficients for these factors across multiple categories. RESULTS: During the study period (2007-2022), the prevalence of AR was more common in females than in males. Particularly in 2022, the prevalence among females was 19.3% (95% confidence interval, 17.3-21.3), while among males, it was 15.6% (13.8-17.4). The prevalence of AD and asthma showed a slight disparity between males and females. Before and during the pandemic, the prevalence of AD and AR showed a continuous increase (AD: from 2.8% [2.5-3.2] in 2007-2009 to 4.7% [3.9-5.4] in 2022; AR: from 11.7% [11.1-12.4] in 2007-2009 to 17.4% [16.0-18.9] in 2022), while asthma maintained a relatively stable trend. Moreover, this study identified several sex-specific factors that seem to be associated with a higher prevalence of allergic diseases in females, such as high household income, smoking, and being overweight or obese. CONCLUSIONS: Throughout all the periods examined, females consistently exhibited a higher prevalence of AR compared to males. Moreover, the risk factors for males and females varied depending on the disease, with females generally facing a greater number of risk factors. Consequently, this study highlights the necessity for sex-specific health interventions and further research to comprehend the complex influence of socioeconomic factors and lifestyle choices on the prevalence and risk of AD, AR, and asthma.

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.

Self-stigma in schizophrenia: a systematic review and meta-analysis of 37 studies from 25 high- and low-to-middle income countries.

In schizophrenia, it is currently thought that stigma experience is increased by psychotic and depressive symptomatology, exposure to stigma at the workplace, and that self-stigma levels vary across countries without knowing the factors explaining these variations. The aim of the present meta-analysis was to synthetize the data of observational studies comprehensively exploring multiple self-stigma dimensions and associated factors. A systematic literature search without language or time restrictions was conducted in Medline, Google Scholar, and Web of Science for studies, last 09/2021. Eligible studies that included ≥80% of patients diagnosed with schizophrenia-spectrum disorders and used a validated scale measuring self-stigma dimensions were meta-analysed using random-effects models, followed by subgroup and meta-regression analyses. Study registration: PROSPERO CRD42020185030. Overall, 37 studies (n = 7717) from 25 countries (5 continents) published between 2007 and 2020 were included, with 20 studies conducted in high-income countries. These studies used two scales with total scores ranging 1-4. The mean estimate of perceived stigma was 2.76 [95% confidence interval (CI) = 2.60-2.94], experienced stigma 2.29 [95% CI = 2.18, 2.41], alienation 2.40 [95% CI = 2.29, 2.52], stereotype endorsement 2.14 [95% CI = 2.03, 2.27], social withdrawal 2.28 [95% CI = 2.17, 2.39] and stigma resistance 2.53 [95% CI = 2.43, 2.63]). Self-stigma levels did not reduce over time. Living outside urban areas, low-income, singleness, unemployment, high antipsychotic dose and low functioning were associated with different stigma dimensions. Some stigma dimensions were lower in studies carried out in Europe compared to other regions. Most studies published since 2007 report that self-stigma is a particular concern for a specific subgroup of patients. This subgroup is characterized by unemployment, high antipsychotic dose and low functioning. We identified important other missing factors that should be explored to improve the effectiveness of public policies and personalized interventions to reduce self-stigma. Importantly, classical illness severity indices (psychotic severity, age at illness onset, illness duration) and sociodemographic variables (age, sex and education) were not associated with self-stigma, moderating previous findings.

Incidence, prevalence, and global burden of ADHD from 1990 to 2019 across 204 countries: data, with critical re-analysis, from the Global Burden of Disease study.

Data on incidence, prevalence and burden of ADHD are crucial for clinicians, patients, and stakeholders. We present the incidence, prevalence, and burden of ADHD globally and across countries from 1990 to 2019 from the Global Burden of Disease (GBD) study. We also: (1) calculated the ADHD prevalence based on data actually collected as opposed to the prevalence estimated by the GBD with data imputation for countries without prevalence data; (2) discussed the GBD estimated ADHD burden in the light of recent meta-analytic evidence on ADHD-related mortality. In 2019, GBD estimated global age-standardized incidence and prevalence of ADHD across the lifespan at 0.061% (95%UI = 0.040-0.087) and 1.13% (95%UI = 0.831-1.494), respectively. ADHD accounted for 0.8% of the global mental disorder DALYs, with mortality set at zero by the GBD. From 1990 to 2019 there was a decrease of -8.75% in the global age-standardized prevalence and of -4.77% in the global age-standardized incidence. The largest increase in incidence, prevalence, and burden from 1990 to 2019 was observed in the USA; the largest decrease occurred in Finland. Incidence, prevalence, and DALYs remained approximately 2.5 times higher in males than females from 1990 to 2019. Incidence peaked at age 5-9 years, and prevalence and DALYs at age 10-14 years. Our re-analysis of data prior to 2013 showed a prevalence in children/adolescents two-fold higher (5.41%, 95% CI: 4.67-6.15%) compared to the corresponding GBD estimated prevalence (2.68%, 1.83-3.72%), with no significant differences between low- and middle- and high-income countries. We also found meta-analytic evidence of significantly increased ADHD-related mortality due to unnatural causes. While it provides the most detailed evidence on temporal trends, as well as on geographic and sex variations in incidence, prevalence, and burden of ADHD, the GBD may have underestimated the ADHD prevalence and burden. Given the influence of the GBD on research and policies, methodological issues should be addressed in its future editions.