A Southeast Asian expert consensus on the management of major depressive disorder with suicidal behavior in adults under 65 years of age.

BACKGROUND: The high prevalence of suicidal behavior among individuals with major depressive disorder (MDD) in Southeast Asia (SEA) underscores the need for optimized management to address depressive symptoms, reduce suicide risk and prevent suicide in these individuals. Given the lack of clear guideline recommendations for assessing and managing these patients, regional consensus-based recommendations which take into account diverse local contexts across SEA may provide useful guidance for clinical practice. METHODS: A narrative literature review and pre-meeting survey were conducted prior to the consensus meeting of an SEA expert panel comprising 13 psychiatrists with clinical experience in managing patients with MDD with suicidal behavior. Utilizing the RAND/UCLA Appropriateness Method, the expert panel developed consensus-based recommendations on the assessment and treatment of adult patients with MDD with suicidal behavior under 65 years. RESULTS: Screening of adult patients under 65 years with MDD for suicide risk using both a validated assessment tool and clinical interview is recommended. An improved suicide risk stratification - incorporating both severity and temporality, or using a prevention-focused risk formulation - should be considered. For a patient with an MDD episode with low risk of suicide, use of antidepressant monotherapy, and psychotherapy in combination with pharmacological treatment are both recommended approaches. For a patient with an MDD episode with high risk of suicide, or imminent risk of suicide requiring rapid clinical response, or for a patient who had received adequate AD but still reported suicidal behavior, recommended treatment strategies include antidepressant augmentation, combination use of psychotherapy or electroconvulsive therapy with pharmacological treatment, and inpatient care. Suicide-specific psychosocial interventions are important for suicide prevention and should also be part of the management of patients with MDD with suicidal behavior. CONCLUSIONS: There are still unmet needs in the assessment of suicide risk and availability of treatment options that can deliver rapid response in patients with MDD with suicidal behavior. These consensus recommendations on the management of adult patients with MDD with suicidal behavior under 65 years may serve as a useful guidance in diverse clinical practices across the SEA region. Clinical judgment based on careful consideration of individual circumstances of each patient remains key to determining the most appropriate treatment option.

Does a "Western Lifestyle" Confer a Higher Burden of Colorectal Cancer? A Comparison of EU15+ Countries versus Global Trends between 1990 and 2019.

The incidence of colorectal cancer (CRC) in the U.S. is declining in adults 50 years and older; however, recent studies suggest an increasing disease burden among adults under age 50. This study aims to compare the incidence, mortality, and mortality-to-incidence ratios (MIRs) of CRC in EU15+ countries to determine if similar age-stratified occurrences are observed across these countries with similar "Western lifestyle"-related risk factors. Incidence and mortality rates for CRC between 1990 and 2019 were extracted using the Global Burden of Disease database. The data were age-stratified into groups between ages 25-49, 50-69, and greater than 69 years. We observed that the incidence of CRC increased globally for all age groups, with the highest increase observed for males (75.9%) and females (27.7%) aged 25-49. A similar trend was observed in 15 of the 19 EU15+ countries for males and 16 of the 19 EU15+ countries for females aged 25-49. Global mortality rates decreased for all age groups in females but increased for males in all age groups. This raises concerns regarding potentially modifiable risk factors contributing to increased CRC development and underscores the importance of implementing standardized screening at an earlier stage to ensure adequate detection in the younger population.

Menopause is associated with increased prevalence of nonalcoholic fatty liver disease: a systematic review and meta-analysis.

IMPORTANCE: Data are inconsistent on whether menopause is a risk for nonalcoholic fatty liver disease (NAFLD). OBJECTIVE: Using systematic review and meta-analysis, we aimed to collect all available data to determine the association between menopause and NAFLD. EVIDENCE REVIEW: Potentially eligible studies were identified from EMBASE, MEDLINE, and Web of Science databases from inception to December 2021 using a search strategy that was composed of the terms for "NAFLD" and "menopause." Eligible study must contain two groups of participants: one group of postmenopausal women and another group of premenopausal women. Then, the study must report the association between menopause and prevalent NAFLD. We extracted such data from each study and calculated pooled odds ratio (OR) by combining effect estimates of each study using a random-effects model. Funnel plot was used to assess for the presence of publication bias. FINDINGS: A total of 587 articles were identified. After two rounds of independent review by two investigators, 12 cross-sectional studies fulfilled the eligibility criteria. The meta-analysis of 12 studies revealed the significant association between menopause and NAFLD with a pooled OR of 2.37 (95% CI, 1.99-2.82; I2 = 73%). The association remained significant in a sensitivity meta-analysis of six studies that reported the association with adjustment for age and metabolic factors with a pooled OR of 2.19 (95% CI, 1.73-2.78; I2 = 74%). The funnel plot was fairly symmetric and was not suggestive of publication bias. CONCLUSIONS AND RELEVANCE: The meta-analysis reveals that menopausal status was associated with approximately 2.4 times higher odds of NAFLD.

Trends in prostate cancer mortality in the United States of America, by state and race, from 1999 to 2019: estimates from the centers for disease control WONDER database.

BACKGROUND: In the United States of America (USA), prostate cancer (PC) is the most common cancer in men and the second cause of cancer mortality. Black men (BM) have a higher incidence and worse mortality when compared to white men (WM). We compared trends in PC mortality in the USA by race and state from 1999 to 2019. METHODS: We extracted PC mortality data from the Centers for Disease Control (CDC) WONDER database using the International Classification of Diseases (ICD) 10 code C61. Age-Standardized Mortality Rates (ASMR) were divided into racial groups and reported by year and state. Due to the lack of available data in many states, analyses were conducted only for WM and BM using Joinpoint regression for trend comparisons. RESULTS: Between 1999-2019, ASMR decreased at the national level in Black (-44.6%), Asian (-44.8%), White (-31.8%), and American Indian or Alaskan native men (-19.0%). ASMR decreased in all states for both races. The greatest drop in ASMR was in Kentucky (-47.0%) for WM and Delaware (-57.8%) for BM. In 2019, ASMRs in BM (13.4/100 000) were significantly higher than WM (7.3/100 000), American Indian or Alaskan Native (3.2/100 000), and Asian men (3.2/100 000) (p < 0.001). The highest ASMRs were in Nebraska (33.5/100 000) for BM and Alaska (11/100 000) for WM. CONCLUSIONS: During the last 20 years, the PC mortality rate dropped in all states for all races, suggesting an advancement in management strategies. Although a higher decrease in ASMR was observed in BM, ASMR remain higher among BM. ASMRs were also found to be increasing in many states post USPSTF guideline change (2012), indicating a need for more education around optimized prostate cancer screening.

Eccrine Carcinoma With an Unknown Primary: Managing Occult Cancer Through Multidisciplinary Tumor Board Collaboration.

Eccrine carcinomas are rare cutaneous cancers that tend to be locally aggressive. Here we report a rare case of a mucinous eccrine carcinoma presenting in axillary lymph nodes without an identifiable primary lesion. This is a 69-year-old male with a past medical history of benign prostatic hyperplasia, melanoma, basal cell carcinoma, hypercholesterolemia, hypertension, and arthritis who was found to have an elevated prostate-specific antigen. Transrectal prostate biopsies confirmed adenocarcinoma of the prostate. A chest CT scan performed for further staging of prostate cancer identified new left axillary lymphadenopathy and positron emission tomography (PET)-CT imaging showed moderate fluorodeoxyglucose (FDG) uptake in the lymph nodes of the left axilla and left subpectoral regions. Lymph node tissue obtained by core needle biopsy demonstrated high-grade carcinoma with a nonspecific immunohistochemical profile. Complete left axillary lymphadenectomy was performed, revealing mucinous eccrine carcinoma. He was started on hormonal therapy for prostate cancer and radiation therapy for axillary eccrine carcinoma at the same time. Based on our literature review, this appears to be the first case of eccrine carcinoma in axillary lymph nodes with an unknown primary. This case is further complicated by synchronous primary prostate cancer. After a multidisciplinary tumor board review, it was decided that his axillary disease should be treated as a primary mucinous carcinoma with complete lymphadenectomy followed by localized radiation. The patient had stable disease at the six-month follow-up. Cancers with unknown primary lesions pose unique challenges in disease management. Without established recommendations or guidelines, multidisciplinary discussions and a collaborative approach are needed.

Health-related quality of life in patients with COVID-19; international development of a patient-reported outcome measure.

BACKGROUND: We aimed to create a questionnaire to assess the health-related quality of life including functioning, symptoms, and general health status of adult patients with current or previous COVID-19. Here, we report on Phase I and II of the development. METHODS: Internationally recognized methodology for questionnaire development was followed. In Phase I, a comprehensive literature review was performed to identify relevant COVID-19 issues. Decisions for inclusion, exclusion, and data extraction were completed independently in teams of two and then compared. The resulting issues were discussed with health care professionals (HCPs) and current and former COVID-19 patients. The input of HCPs and patients was carefully considered, and the list of issues updated. In Phase II, this updated list was operationalized into items/questions. RESULTS: The literature review yielded 3342 publications, 339 of which were selected for full-text review, and 75 issues were identified. Discussions with 44 HCPs from seven countries and 52 patients from six countries showed that psychological symptoms, worries, and reduced functioning lasted the longest for patients, and there were considerable discrepancies between HCPs and patients concerning the importance of some of the symptoms. The final list included 73 issues, which were operationalized into an 80-item questionnaire. CONCLUSION: The resulting COVID-19 questionnaire covers health-related quality of life issues relevant to COVID-19 patients and is available in several languages. The next steps include testing of the applicability and patients' acceptability of the questionnaire (Phase IIIA) and preliminary psychometric testing (Phase IIIB).

Moral competence and conduct disorder among Filipino children in conflict with the law.

AIMS: The numbers of children in conflict with the law continue to rise in Asia, yet few studies have been conducted regarding factors associated with it. It has been theorized that children with conduct disorder represent majority of children in conflict with the law, and that poor moral competence mediates the association between conduct disorder and antisocial behavior. This study aimed to present a profile of Filipino children in conflict with the law, determine the prevalence of conduct disorder in the sample, and investigate variables associated with conduct disorder. METHODS: This was a cross-sectional study conducted at a conflict with the law Custodial Care Center in the Philippines. The procedure entailed a diagnostic interview and questionnaire administration conducted by psychiatrists. Questionnaires administered included the Moral Competence Test and Parental Warmth and Acceptance Scale. Statistical analyses of data included descriptive statistics, chi-square tests, and independent t tests. SPSS v.23.0 was used for data encoding and analysis. RESULTS: Twenty-three participants were included in the study, with 10 participants with conduct disorder and 13 controls. Majority were male adolescents between the ages of 16 and 18 years. Conduct disorder was associated with commission of multiple violations, particularly theft and homicide, the presence of a substance use disorder, and a history of abuse. Participants with conduct disorder had lower moral competence levels compared to participants without conduct disorder. CONCLUSION: Conduct disorder was associated with high-risk antisocial behavior and lower levels of moral competence.

c-Fms-mediated differentiation and priming of monocyte lineage cells play a central role in autoimmune arthritis.

INTRODUCTION: Tyrosine kinases are key mediators of multiple signaling pathways implicated in rheumatoid arthritis (RA). We previously demonstrated that imatinib mesylate--a Food and Drug Administration (FDA)-approved, antineoplastic drug that potently inhibits the tyrosine kinases Abl, c-Kit, platelet-derived growth factor receptor (PDGFR), and c-Fms--ameliorates murine autoimmune arthritis. However, which of the imatinib-targeted kinases is the principal culprit in disease pathogenesis remains unknown. Here we examine the role of c-Fms in autoimmune arthritis. METHODS: We tested the therapeutic efficacy of orally administered imatinib or GW2580, a small molecule that specifically inhibits c-Fms, in three mouse models of RA: collagen-induced arthritis (CIA), anti-collagen antibody-induced arthritis (CAIA), and K/BxN serum transfer-induced arthritis (K/BxN). Efficacy was evaluated by visual scoring of arthritis severity, paw thickness measurements, and histological analysis. We assessed the in vivo effects of imatinib and GW2580 on macrophage infiltration of synovial joints in CIA, and their in vitro effects on macrophage and osteoclast differentiation, and on osteoclast-mediated bone resorption. Further, we determined the effects of imatinib and GW2580 on the ability of macrophage colony-stimulating factor (M-CSF; the ligand for c-Fms) to prime bone marrow-derived macrophages to produce tumor necrosis factor (TNF) upon subsequent Fc receptor ligation. Finally, we measured M-CSF levels in synovial fluid from patients with RA, osteoarthritis (OA), or psoriatic arthritis (PsA), and levels of total and phosphorylated c-Fms in synovial tissue from patients with RA. RESULTS: GW2580 was as efficacious as imatinib in reducing arthritis severity in CIA, CAIA, and K/BxN models of RA. Specific inhibition of c-Fms abrogated (i) infiltration of macrophages into synovial joints of arthritic mice; (ii) differentiation of monocytes into macrophages and osteoclasts; (iii) osteoclast-mediated bone resorption; and (iv) priming of macrophages to produce TNF upon Fc receptor stimulation, an important trigger of synovitis in RA. Expression and activation of c-Fms in RA synovium were high, and levels of M-CSF were higher in RA synovial fluid than in OA or PsA synovial fluid. CONCLUSIONS: These results suggest that c-Fms plays a central role in the pathogenesis of RA by mediating the differentiation and priming of monocyte lineage cells. Therapeutic targeting of c-Fms could provide benefit in RA.

Molecular framework for response to imatinib mesylate in systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease in which the tyrosine kinases platelet-derived growth factor receptor (PDGFR) and Abl are hypothesized to contribute to the fibrosis and vasculopathy of the skin and internal organs. Herein we describe 2 patients with early diffuse cutaneous SSc (dcSSc) who experienced reductions in cutaneous sclerosis in response to therapy with the tyrosine kinase inhibitor imatinib mesylate. Immunohistochemical analyses of skin biopsy specimens demonstrated reductions of phosphorylated PDGFRbeta and Abl with imatinib therapy. By gene expression profiling, an imatinib-responsive signature specific to dcSSc was identified (P < 10(-8)). The response of these patients and the findings of the analyses suggest that PDGFRbeta and Abl play critical, synergistic roles in the pathogenesis of SSc, and that imatinib targets a gene expression program that is frequently dysregulated in dcSSc.