Effectiveness of remote risk-based monitoring and potential benefits for combination with direct data capture.

BACKGROUND: In recent years, alternative monitoring approaches, such as risk-based and remote monitoring techniques, have been recommended instead of traditional on-site monitoring to achieve more efficient monitoring. Remote risk-based monitoring (R2BM) is a monitoring technique that combines risk-based and remote monitoring and focuses on the detection of critical data and process errors. Direct data capture (DDC), which directly collects electronic source data, can facilitate R2BM by minimizing the extent of source documents that must be reviewed and reducing the additional workload on R2BM. In this study, we evaluated the effectiveness of R2BM and the synergistic effect of combining R2BM with DDC. METHODS: R2BM was prospectively conducted with eight participants in a randomized clinical trial using a remote monitoring system that uploaded photographs of source documents to a cloud location. Critical data and processes were verified by R2BM, and later, all were confirmed by on-site monitoring to evaluate the ability of R2BM to detect critical data and process errors and the workload of uploading photographs for clinical trial staff. In addition, the reduction of the number of uploaded photographs was evaluated by assuming that the DDC was introduced for data collection. RESULTS: Of the 4645 data points, 20.9% (n = 973, 95% confidence interval = 19.8-22.2) were identified as critical. All critical data errors corresponding to 5.4% (n = 53/973, 95% confidence interval = 4.1-7.1) of the critical data and critical process errors were detectable by R2BM. The mean number of uploaded photographs and the mean time to upload them per visit per participant were 34.4 ± 11.9 and 26.5 ± 11.8 min (mean ± standard deviation), respectively. When assuming that DDC was introduced for data collection, 45.0% (95% confidence interval = 42.2-47.9) of uploaded photographs for R2BM were reduced. CONCLUSIONS: R2BM can detect 100% of the critical data and process errors without on-site monitoring. Combining R2BM with DDC reduces the workload of R2BM and further improves its efficiency.

The Relationship Between Kiritsu-Meijin-Derived Autonomic Function Parameters and Visual-Field Defects in Eyes with Open-Angle Glaucoma.

PURPOSE: This retrospective cross-sectional study aimed to investigate the association between autonomic parameters measured using the Kiritsu-Meijin device and visual-field defects in patients with open-angle glaucoma. METHODS: A total of 79 eyes of 42 patients with open-angle glaucoma were enrolled in this study. Kiritsu-Meijin testing comprised three phases: sitting, standing, and sitting again (2 min, 2 min, and 1 min, respectively). Continuous electrocardiograms were recorded for five minutes. Autonomic parameters were extracted from the resulting data and analyzed, including activity, balance, reaction, switchover, and recovery; these are five representative parameters derived from Kiritsu-Meijin testing. Correlations between these parameters and mean deviation from Humphrey visual field testing were determined. Additionally, we used a linear mixed-effects model to observe sectoral differences in the relationship between total deviation and the Kiritsu-Meijin parameters. In this study, we focused on superior, central, and inferior total deviations. RESULTS: Significant positive correlations were observed between activity, balance, and recovery and mean deviation values (ß = 0.29-0.38, p < .05). The ß value between activity and inferior total deviation was higher than that between activity and superior total deviation (ß = 0.22, p < .05). Balance did not show any sectoral differences (p > .05). Recovery was more strongly associated with central to inferior total deviation than superior total deviation (ß = 0.17-0.25, p < .05). CONCLUSION: Our findings suggest that in patients with open-angle glaucoma, lower activity and recovery are associated with more severe central and/or inferior visual field defects in the superior quadrant. These results imply that measurements of autonomic function made with the Kiritsu-Meijin device may have clinical utility in the management of glaucoma.

Immunohistochemical detection of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ameloblastomas.

BACKGROUND: To evaluate the roles of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in tumor progression, expression of MMP-1, -2 and -9 and TIMP-1 and -2 was analyzed in ameloblastomas as well as tooth germs. METHODS: Frozen tissue sections of seven tooth germs and 22 ameloblastomas were immunohistochemically examined using anti-MMP-1, -2 and -9 and anti-TIMP-1 and -2 antibodies. RESULTS: MMP-1, -2 and -9 and TIMP-1 and -2 were expressed strongly in mesenchymal components of tooth germs, and stromal cells of ameloblastomas. Immunoreactivity for MMP-9 in stromal cells of ameloblastomas was significantly stronger than in mesenchymal cells of dental follicles and dental papillae. Dental laminae showed weak MMP-2 expression in six tooth germs, MMP-9 expression in two tooth germs and TIMP-1 expression in six tooth germs. Some tumor cells showed weak MMP-2 expression in 19 ameloblastomas, MMP-9 expression in four ameloblastomas and TIMP-1 expression in all cases. TIMP-2 reactivity was prominently found in basement membrane zones of dental laminae in tooth germs, and tumor cell islands or nests in ameloblastomas. CONCLUSION: Expression of MMPs and TIMPs was considered to be associated with interactions between epithelial cells and mesenchymal components in normal and neoplastic odontogenic tissues; these molecules might play a role in regulation of tumor progression in ameloblastomas as well as regulation of developmental processes in tooth germs.

Immunohistochemical detection of hepatocyte growth factor, transforming growth factor-beta and their receptors in epithelial odontogenic tumors.

BACKGROUND: Tumors derived from odontogenic epithelium exhibit considerable variation and are classified into several benign and malignant entities. To clarify the role of growth factors in oncogenesis, cytodifferentiation and progression of epithelial odontogenic tumors, expression of hepatocyte growth factor (HGF), transforming growth factor-beta (TGF-beta) and their receptors were analyzed in these tumors as well as in tooth germs. METHODS: Specimens of five tooth germs, 34 ameloblastomas, three calcifying epithelial odontogenic tumors (CEOTs), two clear cell odontogenic tumors (CCOTs), five adenomatoid odontogenic tumors (AOTs), six calcifying odontogenic cysts (COCs) and six malignant ameloblastomas were examined immunohistochemically with the use of antibodies against HGF, TGF-beta and their receptors. RESULTS: In tooth germs and epithelial odontogenic tumors, immunoreactivity for HGF and TGF-beta was detected in both epithelial and mesenchymal cells, while expression of their receptors was found only in epithelial cells. In tooth germs and main types of ameloblastomas, HGF and TGF-beta reactivity was marked in epithelial cells near the basement membrane, and their receptors were diffusely positive in most epithelial cells. In subtypes of ameloblastomas, reduced expression of HGF, c-Met and TGF-beta and increased reactivity for TGF-beta receptors were detected in keratinizing cells in acanthomatous ameloblastomas, and granular cells in granular cell ameloblastomas demonstrated little or no expression of HGF, TGF-beta or their receptors. As compared with main types of ameloblastomas, basal cell ameloblastomas showed high HGF reactivity, and desmoplastic ameloblastomas exhibited elevated reactivity for TGF-beta and its receptors. Neoplastic cells in CEOTs, AOTs and COCs showed reactivity for HGF, TGF-beta and their receptors. Elevated HGF and TGF-beta reactivity was found in pseudoglandular cells in AOTs, and high expression of their receptors was noted in ghost cells in COCs. Metastasizing ameloblastomas showed similar expression patterns of HGF, TGF-beta and their receptors to those of benign ameloblastomas, while CCOTs and ameloblastic carcinomas had increased HGF expression and low reactivity for TGF-beta and its receptors as compared with benign ameloblastomas. CONCLUSIONS: Immunohistochemical localization of HGF, TGF-beta and their receptors in tooth germs and epithelial odontogenic tumors supports the hypothesis that HGF and TGF-beta act on epithelial cells via paracrine and autocrine mechanisms. Altered expression of the agents in these epithelial odontogenic tumors, especially subtypes of ameloblastomas, AOTs and COCs, suggests that HGF and TGF-beta signaling might affect differentiation of neoplastic odontogenic epithelial cells. Activated HGF/c-Met pathway and reduced TGF-beta signaling in CCOTs and ameloblastic carcinomas may be associated with the malignant potential of these epithelial odontogenic tumors.