Travel-related Twenty-eight Days Cyclical Thrombosis and Subgroups of COVID-19 Cardiac Biomarker Data: Novel Review Strategy and Meta-analysis Method

Backgrounds Strange controversies have remained in thrombosis-related fields (traveler’s and COVID-19-related thrombosis), although traveler’s thrombosis is well-known even among non-professionals as “economy class syndrome.” We hypothesized there might be something overlooked behind those strange situations. Methods Since ordinary review methods (e.g., systematic review or meta-analysis) had already been conducted, we focused on reviewing a “previously published” “chart.” Also, we developed a novel “review method” for the meta-regression analysis result. We applied those to some previously published and well-known data. Results We newly found an approximately 28 days cycle of thrombosis onset over several weeks after travel in a figure. Also, we found an eighteen-day cycle of thrombosis onset in another chart. In COVID-19 cardiovascular biomarker studies, we newly extracted subgroup patterns in a scatterplot (Troponin T and NT-proBNP) that applied simple linear regression analysis. Also, these subgroups had already appeared in the cardiomyopathy study. Conclusions Traveler’s thrombosis sometimes occurs over two months after leaving the risky in-flight environment. This phenomenon has been explained that the thrombus is formed in a cabin but dislodged after. However, from the cyclic patterns, explaining that the “high-risk period of thrombosis with Oral Contraceptive (OC) use initiation” coincided with “travel” is more reasonable (e.g., honeymoon and OC initiation). Regarding risk-benefit balance, it is conceivable that “spreading the risk” by starting the dosing away from the travel period is essential to ensure safer use because the in-flight environment may have a non-zero effect, and optimal care by a primary care physician (prescriber) is not available during the travel. In COVID-19, there seems to be a complex scatterplot structure that is unsuitable for usually used simple linear fitting. In a literature review, a pattern on a chart should be given more paying attention. ### Competing Interest Statement Munekazu Yamakuchi, Kazunori Takenouchi, and Teruto Hashiguchi have completed the Unified Competing Interest form and declare: no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work. Keiichiro Kimoto has been in charge of external advisor for the Data Strategy Research Institute but received no financial support for this study. ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was not required ethical approval because the study used ONLY two types of openly available human data. Firstly, this study performed meta-analyses as secondary analyses. The source of the data was described in the method section. Second, this study analyzed measured values from figures in previous published scientific papers. All the figures were appropriately treated with careful attention to the copyright issues to protect the integrity of the science. The sources of the original articles were described in the figure legend following the copyright holder's instructions. Also, we submit copyright details in another file to a journal that we submit this manuscript file to explain additional information. This study suggests a new review strategy and meta-analysis method for exploratory data analysis and reports some epidemiological findings. So, there were no applicable guidelines (e.g., Preferred Reporting Items for Systematic reviews and Meta-Analyses, PRISMA). However, this study carefully follows the usage of the statistical analysis method, and the whole process is precisely described in the method details section and Fig. 2. This study was not received financial support from any funding. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes We analyzed clinical data published by other studies (third parties). Used data is identified by indicated information of citation (reference numbers and list of references). The corresponding author responds to inquiries in the case of measured values from published figures requested by reviewers or readers.