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.

Cardiovascular and cerebrovascular adverse events associated with intravitreal anti-vascular endothelial growth factor monoclonal antibodies: a World Health Organization pharmacovigilance study.

PURPOSE: To analyze cardiovascular and cerebrovascular adverse events (ADRs) after intravitreal anti-vascular endothelial growth factor (VEGF; aflibercept, bevacizumab, brolucizumab, and ranibizumab) treatment. SUBJECTS: VigiBase, a World Health Organization (WHO) global safety report database DESIGN: Pharmacovigilance study METHODS: The individual-case-safety reports (ICSR) of cardiovascular and cerebrovascular ADRs after intravitreal anti-VEGF treatment were compared with those reported in the full database. From 2004 to 2023, 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 (IC) were calculated, and the 95% lower credibility interval endpoint of the information component (IC025) was used for disproportionate Bayesian reporting. Inter-drug comparisons were performed using the ratio of odd 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]), arrythemias 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 to ranibizumab, patients with 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, significantly increased reporting of cardiovascular and cerebrovascular ADRs were identified after intravitreal anti-VEGF treatment. While 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.

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

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

Protocol for the development of a reporting guideline for umbrella reviews on epidemiological associations using cross-sectional, case-control and cohort studies: the Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC).

INTRODUCTION: Observational studies are fraught with several biases including reverse causation and residual confounding. Overview of reviews of observational studies (ie, umbrella reviews) synthesise systematic reviews with or without meta-analyses of cross-sectional, case-control and cohort studies, and may also aid in the grading of the credibility of reported associations. The number of published umbrella reviews has been increasing. Recently, a reporting guideline for overviews of reviews of healthcare interventions (Preferred Reporting Items for Overviews of Reviews (PRIOR)) was published, but the field lacks reporting guidelines for umbrella reviews of observational studies. Our aim is to develop a reporting guideline for umbrella reviews on cross-sectional, case-control and cohort studies assessing epidemiological associations. METHODS AND ANALYSIS: We will adhere to established guidance and prepare a PRIOR extension for systematic reviews of cross-sectional, case-control and cohort studies testing epidemiological associations between an exposure and an outcome, namely Preferred Reporting Items for Umbrella Reviews of Cross-sectional, Case-control and Cohort studies (PRIUR-CCC). Step 1 will be the project launch to identify stakeholders. Step 2 will be a literature review of available guidance to conduct umbrella reviews. Step 3 will be an online Delphi study sampling 100 participants among authors and editors of umbrella reviews. Step 4 will encompass the finalisation of PRIUR-CCC statement, including a checklist, a flow diagram, explanation and elaboration document. Deliverables will be (i) identifying stakeholders to involve according to relevant expertise and end-user groups, with an equity, diversity and inclusion lens; (ii) completing a narrative review of methodological guidance on how to conduct umbrella reviews, a narrative review of methodology and reporting in published umbrella reviews and preparing an initial PRIUR-CCC checklist for Delphi study round 1; (iii) preparing a PRIUR-CCC checklist with guidance after Delphi study; (iv) publishing and disseminating PRIUR-CCC statement. ETHICS AND DISSEMINATION: PRIUR-CCC has been approved by The Ottawa Health Science Network Research Ethics Board and has obtained consent (20220639-01H). Participants to step 3 will give informed consent. PRIUR-CCC steps will be published in a peer-reviewed journal and will guide reporting of umbrella reviews on epidemiological associations.

Association between self-reported visual symptoms (suggesting cataract) and self-reported fall-related injury among adults aged ≥ 65 years from five low- and middle-income countries.

BACKGROUND: Cataracts may increase risk for falls but studies on this topic from low- and middle-income countries (LMICs) are scarce. Therefore, we examined the cross-sectional association between self-reported visual symptoms (suggesting cataract) and self-reported injurious falls in nationally representative samples of adults aged ≥ 65 years from five LMICs (China, Ghana, India, Mexico, and Russia). METHODS: Data from the WHO Study on global AGEing and adult health (SAGE) were analysed. Self-reported information on past 12-month fall-related injury and cataract based on symptoms were collected. Multivariable logistic regression and meta-analyses were conducted to assess associations. RESULTS: Data on 13,101 people aged ≥ 65 years were analysed [mean (SD) age 72.5 (11.3) years; 45.2% males]. The overall prevalence of self-reported fall-related injury and visual symptoms (suggesting cataract) were 4.9% and 29.4%, respectively. There was a positive association between self-reported visual symptoms (suggesting cataract) and fall-related injury (i.e., OR > 1) in all five countries but statistical significance was reached in three: China (OR = 1.60; 95% CI = 1.08-2.35), India (OR = 1.96; 95% CI = 1.15-3.35), and Russia (OR = 3.58; 95% CI = 2.06-6.24). The pooled OR including all five countries based on a meta-analysis was OR = 1.88 (95% CI = 1.32-2.68). CONCLUSIONS: Self-reported visual symptoms (suggesting cataract) were associated with higher odds for self-reported injurious falls among older adults in LMICs. Expanding availability of cataract surgery in LMICs may also have the additional benefit of reducing falls among older people.

The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.

Association between sedentary behavior and dynapenic abdominal obesity among older adults from low- and middle-income countries.

BACKGROUND: Sedentary behavior, or time spent sitting, may increase risk for dynapenic abdominal obesity (DAO), but there are currently no studies on this topic. AIMS: Therefore, we investigated the association between sedentary behaviour and DAO in a nationally representative sample of older adults from six low- and middle-income countries. METHODS: Cross-sectional data from the Study on Global AGEing and Adult Health were analysed. Dynapenia was defined as handgrip strength < 26 kg for men and < 16 kg for women. Abdominal obesity was defined as waist circumference of > 88 cm (> 80 cm for Asian countries) for women and > 102 cm (> 90 cm) for men. DAO was defined as having both dynapenia and abdominal obesity. Self-reported sedentary behavior was categorized as ≥ 8 h/day (high sedentary behaviour) or < 8 h/day. Multivariable multinomial logistic regression was conducted. RESULTS: Data on 20,198 adults aged ≥ 60 years were analyzed [mean (SD) age 69.3 (13.1) years; 54.1% females]. In the overall sample, ≥ 8 h of sedentary behavior per day (vs. <8 h) was significantly associated with 1.52 (95%CI = 1.11-2.07) times higher odds for DAO (vs. no dynapenia and no abdominal obesity), and this was particularly pronounced among males (OR = 2.27; 95%CI = 1.42-3.62). Highly sedentary behavior was not significantly associated with dynapenia alone or abdominal obesity alone. DISCUSSION: High sedentary behaviour may increase risk for DAO among older adults. CONCLUSIONS: Interventions to reduce sedentary behaviour may also lead to reduction of DAO and its adverse health outcomes, especially among males, pending future longitudinal research.

Prenatal opioid exposure and subsequent risk of neuropsychiatric disorders in children: nationwide birth cohort study in South Korea.

OBJECTIVE: To investigate the potential association between prenatal opioid exposure and the risk of neuropsychiatric disorders in children. DESIGN: Nationwide birth cohort study. SETTING: From 1 January 2009 to 31 December 2020, birth cohort data of pregnant women in South Korea linked to their liveborn infants from the National Health Insurance Service of South Korea were collected. PARTICIPANTS: All 3 251 594 infants (paired mothers, n=2 369 322; age 32.1 years (standard deviation 4.2)) in South Korea from the start of 2010 to the end of 2017, with follow-up from the date of birth until the date of death or 31 December 2020, were included. MAIN OUTCOME MEASURES: Diagnosis of neuropsychiatric disorders in liveborn infants with mental and behaviour disorders (International Classification of Diseases 10th edition codes F00-99). Follow-up continued until the first diagnosis of neuropsychiatric disorder, 31 December 2020 (end of the study period), or the date of death, whichever occurred first. Eight cohorts were created: three cohorts (full unmatched, propensity score matched, and child screening cohorts) were formed, all of which were paired with sibling comparison cohorts, in addition to two more propensity score groups. Multiple subgroup analyses were performed. RESULTS: Of the 3 128 571 infants included (from 2 299 664 mothers), we identified 2 912 559 (51.3% male, 48.7% female) infants with no prenatal opioid exposure and 216 012 (51.2% male, 48.8% female) infants with prenatal opioid exposure. The risk of neuropsychiatric disorders in the child with prenatal opioid exposure was 1.07 (95% confidence interval 1.05 to 1.10) for fully adjusted hazard ratio in the matched cohort, but no significant association was noted in the sibling comparison cohort (hazard ratio 1.00 (0.93 to 1.07)). Prenatal opioid exposure during the first trimester (1.11 (1.07 to 1.15)), higher opioid doses (1.15 (1.09 to 1.21)), and long term opioid use of 60 days or more (1.95 (1.24 to 3.06)) were associated with an increased risk of neuropsychiatric disorders in the child. Prenatal opioid exposure modestly increased the risk of severe neuropsychiatric disorders (1.30 (1.15 to 1.46)), mood disorders, attention deficit hyperactivity disorder, and intellectual disability in the child. CONCLUSIONS: Opioid use during pregnancy was not associated with a substantial increase in the risk of neuropsychiatric disorders in the offspring. A slightly increased risk of neuropsychiatric disorders was observed, but this should not be considered clinically meaningful given the observational nature of the study, and limited to high opioid dose, more than one opioid used, longer duration of exposure, opioid exposure during early pregnancy, and only to some neuropsychiatric disorders.

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.

Association of handgrip strength with suicidal ideation among adults aged ≥50 years from low- and middle-income countries.

INTRODUCTION: This study aimed to investigate the association between handgrip strength and suicidal ideation in representative samples of adults aged ≥50 years from six LMICs (China, Ghana, India, Mexico, Russia, and South Africa). METHODS: Cross-sectional, community-based data from the World Health Organization's Study on Global Aging and Adult Health were analyzed. Handgrip strength quintiles by sex were created based on the average value of two handgrip measurements of the dominant hand. Self-reported information on past 12-month suicidal ideation was collected. Multivariable logistic regression analysis was conducted to assess associations. RESULTS: Data on 34,129 individuals were analyzed [mean (SD) age 62.4 (16.0) years; age range 50-114 years; 52.1% females]. After adjustment for potential confounders, in the overall sample, compared to the handgrip strength quintile with the highest values [Quintile 1 (Q1)], Q2, Q3, Q4, and Q5 were associated with significant 2.15 (95% CI = 1.05-4.39), 2.78 (95% CI = 1.06-7.32), 3.53 (95% CI = 1.68-7.42), and 6.79 (95% CI = 2.80-16.48) times higher odds for suicidal ideation. CONCLUSIONS: Lower handgrip strength was significantly and dose-dependently associated with higher odds for suicidal ideation in adults aged ≥50 years from LMICs. Future longitudinal studies are needed to understand the underlying mechanisms, and whether increasing general muscular strength and physical function may lead to reduction in suicidal ideation.

Physical activity and prevention of mental health complications: An umbrella review.

The potential of physical activity in preventing mental health issues has garnered interest among health professionals. We conducted a systematic umbrella review of evidence supporting the relationship between physical activity and the prevention of mental health complications. Our findings revealed a significant association between higher physical activity levels and reduced risk of depression (OR = 0.77, 95% CI 0.72 - 0.82). This association was consistent across various age groups, sex, and geographical regions. Interestingly, low and moderate-intensity physical activity showed the most significant protective effects against depression (low-intensity: OR = 0.81, 95% CI: 0.75-0.56; moderate-intensity: OR = 0.79, 95% CI: 0.72-0.87). Our analysis also showed significant associations between higher physical activity levels and prevention of anxiety disorders (OR = 0.71, 95% CI: 0.61-0.82). However, the evidence regarding the association between physical activity and psychosis/schizophrenia risk was less clear. These findings underscore the physical activity's potential as a preventative measure against mental health complications, highlighting the importance of promoting physical activity in mental health interventions.

Histopathologic fate of resected pulmonary pure ground glass nodule: a systematic review and meta-analysis.

Background: Pure ground glass nodules (GGNs) have been increasingly detected through lung cancer screening programs. However, there were limited reports about pathologic characteristics of pure GGN. Here we presented a meta-analysis of the histologic outcome and proportion analysis of pure GGN. Methods: This study included previous pathological reports of pure GGN published until June 14, 2022 following a systematic search. A meta-analysis estimated the summary effects and between-study heterogeneity for pathologic diagnosis of invasive adenocarcinoma (IA), minimally invasive adenocarcinoma (MIA), adenocarcinoma in situ (AIS), and atypical adenomatous hyperplasia (AAH). Results: This study incorporated 24 studies with 3,845 cases of pure GGN that underwent surgery. Among them, sublobar resection was undertaken in 60% of the patients [95% confidence interval (CI): 38-78%, I2=95%]. The proportion of IA in cases of resected pure GGN was 27% (95% CI: 18-37%, I2=95%), and 50% of IA had non-lepidic predominant patterns (95% CI: 35-65%, I2=91%). The pooled proportions of MIA, AIS, and AAH were 24%, 36%, and 11%, respectively. Among nine studies with available clinical outcomes, no recurrences or metastases was observed other than one study. Conclusions: The portion of IA in cases of pure GGN is significantly larger that expected. More than half of them owned invasiveness components if MIA and IA were combined. Furthermore, there were quite number of lesions with aggressive histologic patterns other than the lepidic subtype. Therefore, further attempts are necessary to differentiate advanced histologic subtype among radiologically favorable pure GGN.

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: A nationwide birth cohort study in South Korea.

BACKGROUND: There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. METHODS: Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. RESULTS: During the follow-up period (median 6.92 years [IQR, 4.72-9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04-1.09] and postnatal [HR, 1.05; 95% CI, 1.01-1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. CONCLUSION: This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

BACKGROUND: Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. METHODS: We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. RESULTS: Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. CONCLUSIONS: This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Prognostic significance of tumour budding in noncolorectal gastrointestinal tract and pancreatobiliary tract: a systematic review and meta-analysis.

Tumour budding shows promise as a prognostic factor in various cancers, but its widespread application is hindered by the lack of large, validated studies and standardized criteria. This meta-analysis aims to review and examine the prognostic role of tumour budding specifically in noncolorectal gastrointestinal and pancreatobiliary tract cancers, broadening our perspective on its clinical relevance. The literature review was conducted through PubMed, Embase, and Web of Science from inception till 20 February 2023. Pooled odds ratio (OR) and hazard ratio (HR) with 95% confidence interval (CI) were calculated to assess the relation between tumour budding and clinicopathologic features, as well as overall survival. Each study was evaluated using the Newcastle-Ottawa Scale and both heterogeneity and publication bias were analysed. In this meta-analysis of 57 studies across various cancer types, multivariate HR revealed worse overall survival in oesophageal squamous cell carcinoma (HR 3.34 [95% CI 2.21-5.04]), gastric adenocarcinoma (2.03 [1.38-2.99]), pancreatic ductal adenocarcinoma (2.56 [2.02-3.25]), and biliary tract adenocarcinoma (3.11 [2.46-3.93]) with high-grade tumour budding. Additionally, high-grade tumour budding consistently correlated with adverse clinicopathological features, including lymph node metastasis, lymphovascular invasion, and distant metastasis without any observed inverse association. High heterogeneity was noted. Our study suggests that tumour budding is a valuable prognostic marker in various cancers. Nonetheless, standardized criteria tailored to specific organ types are necessary to enhance its clinical utility.

Temporal Trends of Physical Fights and Physical Attacks Among Adolescents Aged 12-15 years From 30 Countries From Africa, Asia, and the Americas.

PURPOSE: There is a scarcity of literature on temporal trends in physical fighting and physical attacks among the global adolescent population. Therefore, we aimed to examine these trends in a nationally representative sample of school-going adolescents aged 12-15 years from 30 countries in Africa, Asia, and the Americas, for which temporal trends of physical fighting and physical attacks are largely unknown. METHODS: Cross-sectional data from the Global School-based Student Health Survey 2003-2017 were analyzed. Self-reported data on past 12-month physical fights and physical attacks were collected. For each survey, the prevalence and 95% confidence interval of physical fights and physical attacks were calculated. Linear regression models were used to examine crude linear trends. RESULTS: Data on 190,493 students aged 12-15 years were analyzed [mean (standard deviation) age 13.7 (1.0) years; 48.9% boys]. The mean prevalence of past 12-month physical fight and physical attack was 36.5% and 37.2%, respectively. Significant decreasing trends in physical fights were observed in 16/30 countries, while significant increasing trends were found in 2/30 countries. For physical attacks, significant decreasing and increasing trends were observed in 13/26 and 1/26 countries, respectively. The remaining countries showed stable trends. DISCUSSION: It is encouraging that decreasing trends in physical fighting and physical attacks were observed across a large number of countries. However, stable trends were also common, while increasing trends also existed, suggesting that global efforts to address adolescent violence are still required.

Longitudinal progression trajectory of estimated glomerular filtration rate in children with chronic kidney disease: results from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease).

Background: The natural course of chronic kidney disease (CKD) progression in children varies according to their underlying conditions. This study aims to identify different patterns of subsequent decline in kidney function and investigate factors associated with different patterns of estimated glomerular filtration rate (eGFR) trajectories. Methods: We analyzed data from the KNOW-Ped CKD (KoreaN cohort study for Outcomes in patients With Pediatric Chronic Kidney Disease), which is a longitudinal, prospective cohort study. A latent class linear mixed model was applied to identify the trajectory groups. Results: In a total of 287 patients, the median baseline eGFR (mL/min/1.73 m2) was 63.3, and the median age was 11.5 years. The eGFR decline rate was -1.54 during a 6.0-year follow-up. The eGFR trajectory over time was classified into four groups. Classes 1 (n = 103) and 2 (n = 11) had a slightly reduced eGFR at enrollment with a stable trend (ΔeGFR, 0.2/year) and a rapid decline eGFR over time (ΔeGFR, -10.5/year), respectively. Class 3 had a normal eGFR (n = 16), and class 4 had a moderately reduced eGFR (n = 157); both these chasses showed a linear decline in eGFR over time (ΔeGFR, -4.1 and -2.4/year). In comparison with classes 1 and 2, after adjusting for age, causes of primary renal disease, and baseline eGFR, nephrotic-range proteinuria was associated with a rapid decline in eGFR (odds ratio, 8.13). Conclusion: We identified four clinically relevant subgroups of kidney function trajectories in children with CKD. Most children showed a linear decline in eGFR; however, there are different patterns of eGFR trajectories.

Global prevalence of functional dyspepsia according to Rome criteria, 1990-2020: a systematic review and meta-analysis.

Although functional dyspepsia (FD) is a common functional gastroduodenal disorder with a high socioeconomic burden, little is known about its global prevalence. Thus, we performed a comprehensive study to estimate long-term trends in the prevalence of FD. We searched PubMed/MEDLINE, Embase, and Google Scholar from 1990 to 2022 for population-based studies that reported the prevalence of FD in adults (≥ 18 years old) according to Rome I, II, III, or IV criteria. The prevalence of FD was extracted from included studies to obtain pooled prevalence with 95% confidence intervals (CI) and 95% prediction intervals. Subgroup analysis was performed according to certain characteristics, including geographic region. A total of 44 studies met the eligibility criteria, including 256,915 participants from 40 countries across six continents. The overall global pooled prevalence of FD was 8.4% (95% CI 7.4-.9.5). The prevalence was the highest in Rome I (11.9%; 95% CI 5.1-25.4) and lowest in Rome IV (6.8%; 95% CI 5.8-7.9). Developing countries showed a higher prevalence than developed countries (9.1% versus 8.0%), and prevalence was higher in women, irrespective of the definition used (9.0% versus 7.0%). The pooled prevalence gradually decreased from 1990 to 2020 (12.4% [8.2-18.3] in 1990-2002 versus 7.3% [6.1-8.7] in 2013-2020). The prevalence of FD differs by country, economic status, geographical region, and sex, and the global prevalence has been gradually declining. Despite the heterogeneity of sample population, our study estimates the current global burden of FD and provides information to heath care policy decisions.