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Background: No head-to-head clinical trials have compared the differences in adverse events (AEs) between nivolumab plus ipilimumab (NIVO-IPI) and nivolumab plus cabozantinib (NIVO-CABO) in the treatment of metastatic renal cell carcinoma (mRCC)., Aim: We analysed the two largest real-world databases, the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization's VigiBase, to elucidate the differences in AEs between NIVO-IPI and NIVO-CABO., Method: In total, 40,376 and 38,022 records were extracted from FAERS and VigiBase, and 193 AEs were analysed. The reporting odds ratios (ROR) with 95% confidence interval were calculated using a disproportionality analysis (NIVO-CABO/NIVO-IPI)., Results: The reported numbers of immune-related AEs, including myocarditis, colitis, and hepatitis, were significantly higher with NIVO-IPI (ROR = 0.18 for FAERS and 0.13 for VigiBase). Contrarily, the reported numbers of other AEs, including gastrointestinal disorders (ROR = 2.68 and 2.92) and skin and subcutaneous tissue disorders (ROR = 2.94 and 3.55), considered to be potentiated by the combination of NIVO and CABO, were higher with NIVO-CABO., Conclusion: Our findings contribute to the selection and clinical management of NIVO-IPI and NIVO-CABO, which minimizes the risk of AEs for individual patients with mRCC by considering distinctive differences in the AE profiles., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

No head-to-head postmarket surveillance study has compared the differences in adverse events (AEs) between two combination therapies, axitinib (AXI) + pembrolizumab (PEMBRO) and lenvatinib (LEN) + PEMBRO, against metastatic renal cell carcinoma. This study aims to highlight the comprehensive differences in AEs between these two therapies based on the real-world big data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. In total, 28 937 records were extracted from the FAERS database, and 139 AEs grouped into the System Organ Class according to the Medical Dictionary for Regulatory Activities were analysed. Logistic regression analyses were performed, and the reporting odds ratio with a 95% confidence interval was determined. We found that the incidences of cardiac and hepatobiliary disorders for AXI + PEMBRO, and blood and lymphatic system, metabolism and nutrition, and vascular disorders for LEN + PEMBRO, all of which were associated with serious AEs, were higher than those for LEN + PEMBRO and AXI + PEMBRO, respectively. The differences in the AEs between AXI + PEMBRO and LEN + PEMBRO were not derived merely from those between AXI and LEN monotherapies. Furthermore, remarkable AE potentiation was observed for AXI + PEMBRO. As FAERS is a spontaneous reporting system comprising partially limited information, analysing more detailed relationships between AEs and patient or treatment characteristics was challenging in this study. The present study is the first to show the overall real-world postmarketing differences in AEs between AXI + PEMBRO and LEN + PEMBRO. Our novel findings will substantially improve clinical practice; we recommend comparing patients' conditions associated with the above AEs when selecting between these two therapies. PATIENT SUMMARY: Herein, we highlight the differences in adverse events (AEs) between axitinib + pembrolizumab and lenvatinib + pembrolizumab therapies using data from the real-world Food and Drug Administration Adverse Event Reporting System database aimed at patients with metastatic renal cell carcinoma. We identified AEs that needed attention in each combination. We recommend the differences in AEs to be considered when selecting these two therapies., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren's syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population. Key Points • The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity. • The EULAR/ACR-2019 criteria more frequently misclassified non-SLE patients who did not have SLE, especially those with MCTD or pSS, as having SLE than the previous criteria in patients with childhood onset. • The weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be a more appropriate classification of SLE for a pediatric population., (© 2022. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic 'fashions', and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health,lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts., (Copyright 2010 S. Karger AG, Basel.)

Symptom endorsements and item response patterns on the anxiety-present and anxiety-absent items of the State-Trait Anxiety Inventory Form Y (Spielberger, 1983) for 149 Japanese (99 living in Japan and 50 studying in the United States) and 76 American university students were compared. Although mean scores for the state and trait anxiety-absent items were comparable for Japanese students living in Japan and Japanese international students studying in the United States, the scores of both Japanese groups were significantly higher than those of American students. These differences were attributable to much higher scores of Japanese students on anxiety-absent items that corresponded to a lack of positive feelings. Japanese students had a tendency to inhibit positive (anxiety-absent) feelings, resulting in higher anxiety scores. Responses to anxiety-present and anxiety-absent items should be considered independently in scoring anxiety scales.

Symptom endorsements and response patterns of 1,862 Japanese adult workers (1,509 males and 353 females) to the Japanese adaptation of the State-Trait Anxiety Inventory Form Y (STAI-JY) items, were examined in this study. The mean STAI-JY State and Trait anxiety scores of Japanese workers were substantially higher than those of American workers reported in the Manual, due primarily to the much higher scores of Japanese workers in responding to the anxiety-absent items. The correlations between the State and Trait anxiety-present scales and those of their anxiety-absent scales' counterparts were higher than those between the State anxiety-present and -absent scales and those of their Trait scales' counterparts. These findings suggested that responses to anxiety-present and -absent items should be considered independently in scoring the STAI-JY scales in Japanese working adults.

The Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D) was subjected to principal component (PC) analysis with oblique rotation, as well as an examination of internal consistency, using data obtained from 2,016 adult employees aged 19-63 years. Analyses focused on age differences in these psychometric properties of the CES-D. Coefficient-alpha was sufficiently high for all age groups but was lower than reported in U.S. studies. Positive affect items lowered internal consistency. The PC analyses extracted four factors for each age group. Depressive affect items did not group into one factor; some were combined with somatic or interpersonal items, and the remainder constituted the smallest factor. These three main factors, 'somatic+depressed', interpersonal + negative' and 'positive affect' were comparable across age groups except for those aged 50-63 years. For those aged 50-63 years, the first two factors were combined into a large 'general dysphoria' factor, suggesting a more unified conceptualization of depressive mood. Although 'positive affect' was stable cross-culturally, it was not related to depressive symptomatology as measured by the other items, for Japanese. The 'interpersonal + negative' appears unique for Japanese, indicating the association of interpersonal relations with depressive mood in Japanese. The effects of age-specific ethnocultural factors in Japan on depressive symptomatology are discussed.

Response patterns on the Center for Epidemiologic Studies Depression Scale (CES-D) items among Japanese adolescents were compared with those of their U.S. counterparts. The data were obtained from approximately 1,500 junior high school students, aged 12-15 years. Japanese responses to positively worded items markedly differed from those of American adolescents, whereas responses to negatively worded items were comparable in the two groups. This resulted in poor psychometric properties for the CES-D and spurious higher positive subscale and whole scale scores among the Japanese sample. It is possible that Japanese respondents tend to suppress positive affect expression and, thus, the positively worded questioning is presumably inappropriate for Japanese samples.