ABSTRACT
BACKGROUND: Guideline adaptation is an emerging field to provide more appropriate recommendations for local clinical practice quality and to promote global health equity. However, its utilization status, adaptation procedures, and related materials remain to be studied. METHODS: This study developed a quality improvement protocol for a study as the Development, Evaluation, and impLemenTation for guideline Adaptation (DELTA) study. Current adapted clinical practice guidelines (CPGs) will be systematically searched. Their characteristics, utilization status, and adaptation procedures will be extracted, compared, and analyzed. Whether these adapted CPGs rigorously followed the instruments and steps of adaptation frameworks will also be appraised. In addition, the advantages and limitations of current adaptation methods and their suitable application situations will be analyzed. In addition, future perspectives as DELTA series and DELTA system, aiming for comprehensively evaluating current needs for guideline adaptation and developing a unified framework and related materials were proposed to improve the acceptability, applicability, and implementation of guideline adaptation in clinical practice. The DELTA series are divided into four phases: phase I in analyzing status, characteristics, and procedures and completeness of adapted CPGs; phase II in analyzing differences, heterogeneity, and implementation between adapted and original CPGs; and phase III in collecting, analyzing, and comparing all available adaptation materials. With these research bases, an international working group will be established in phase IV and will develop unified guideline adaptation materials after Delphi consensus, including adaptation frameworks, appraisal tools and checklists, registries, and databases. DISCUSSION: Guideline adaptation has been advanced as an efficient way to guide local clinical practice. However, it still faces several major challenges. The proposed DELTA study, series, and system will further contribute to this emerging topic. TRIAL REGISTRATION: This study has been registered by the PROSPERO international database. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=400170 .
Subject(s)
Global Health , Quality Improvement , Humans , Checklist , Consensus , Databases, Factual , Guidelines as TopicABSTRACT
Brain metastasis is a severe complication that affects the survival of lung cancer patients. However, the mechanism of brain metastasis in lung cancer remains unclear. In this study, we constructed an in vitro BBB model and found that cells from the high-metastatic nonsmall cell lung cancer (NSCLC) cell line H1299 showed a higher capacity to pass through the blood-brain barrier (BBB), as verified by Transwell assays, than cells from the low-metastatic NSCLC cell line A549. Brain microvascular endothelial cells (BMECs) could internalize H1299-derived exosomes, which remarkably promoted A549 cells across the BBB. The BBB-associated exosomal long noncoding RNA (lncRNA) was selected from the RNA-Seq dataset (GSE126548) and verified by real-time PCR and Transwell assays. LncRNA LINC01356 was significantly upregulated in H1299 cells and exosomes derived from these cells compared to that of A549 cells. Moreover, LINC01356 was also upregulated in serum exosomes of patients with NSCLC with brain metastasis compared with those without metastasis. In addition, BMECs treated with LINC01356-deprived exosomes expressed higher junction proteins than those treated with the control exosomes, and silencing LINC01356 in exosomes derived from H1299 cells could inhibit A549 cells from crossing the BBB. These data might indicate that the exosomal lncRNA LINC01356 derived from brain metastatic NSCLC cells plays a key role in remodeling the BBB system, thereby participating in brain metastasis in lung cancer.