ABSTRACT
Strict social isolation and physical distancing measures implemented during the COVID-19 pandemic had significant implications for the psychological well-being of middle-aged and older adults. This study aimed to investigate factors associated with depressive symptoms during the pandemic period among individuals who reported no significant depressive symptoms before the pandemic. Individuals from the Korean Longitudinal Study of Aging without a previous report of significant depressive symptoms across Waves 6 (2016) and 7 (2018) were investigated for the development of depressive symptoms in Wave 8 (2020). The multivariable logistic regression results revealed that both men and women who participated in social gatherings and physical exercise less than once a week were associated with an increase in the likelihood of depressive symptoms (odds ratio [OR] 2.88; 95% confidence interval [CI] 1.80-4.61 and OR 2.61; 95% CI 1.64-4.15, respectively for men and OR 2.58; 95% CI 1.80-3.70 and OR 1.51; 95% CI 1.02-2.23, respectively for women). In addition, unmarried men (OR 2.38; 95% CI 1.37-4.14) and women with one chronic disease (OR 1.98; 95% CI 1.14-3.43) or two or more chronic diseases (OR 2.28; 95% CI 1.31-3.99) reported a significant increase in the likelihood of depressive symptoms. Regular social gatherings and physical exercise were identified as key factors in mitigating depressive symptoms among middle-aged and older adults. The findings can inform the development of public health strategies that promote regular social interactions and physical activity to enhance the psychological resilience and overall well-being of middle-aged and older adults in the endemic era.
ABSTRACT
PURPOSE: Leptomeningeal metastases (LMs) exhibit a high incidence in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) post-treatment with first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). This investigation evaluates the efficacy, safety, and pharmacokinetics of 80 mg once daily osimertinib in patients with LMs resistant to prior first- or second-generation EGFR TKIs. MATERIALS AND METHODS: In this phase II multicenter, open-label, single-arm study, 80 mg osimertinib was administered to patients with EGFR-mutated NSCLC who had developed LMs subsequent to treatment with prior EGFR TKIs. The primary end point was overall survival (OS), assessed alongside objective response rate by the blinded independent central review (BICR) and a pharmacokinetic analysis of plasma and cerebrospinal fluid (CSF) on the first day of cycles 3 and 6. RESULTS: A total of 73 patients diagnosed with LM were treated with osimertinib, including 64 patients evaluable for the LM efficacy set-T790M negative (n = 62) and T790M positive (n = 2). The median OS in the full-analysis set was 15.6 months (95% CI, 11.5 to 20.2). The objective response rate for LM was 51.6%, including a 15.6% complete response, and the disease control rate was 81.3% by BICR in the LM efficacy evaluable set. The median LM progression-free survival by BICR was 11.2 months (95% CI, 7.7 to 15.3), the duration of response was 12.6 months (95% CI, 7.6 to 17.7), and OS was 15.0 months (95% CI, 11.3 to 18.7). Pharmacokinetic analysis showed that the CSF to free plasma osimertinib ratio was 22%. Most safety profiles were grade 1 and 2. CONCLUSION: The study demonstrates significant intracranial efficacy and survival benefits of 80 mg once daily osimertinib in NSCLC patients with LMs. The data support considering daily 80 mg of osimertinib as a treatment option for EGFR-mutated NSCLC patients with LMs, irrespective of T790M mutation status.