Circadian Rhythm and Risk of Hemorrhagic Transformation after AcuteIschemic Stroke Treated with Intravenous Thrombolysis - A SystematicReview
Bibliographic record
Abstract
BACKGROUND: A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However, data assessing the circadian distribution of hemorrhagic transformation after intravenous thrombolysis (ivT) are still incongruent. OBJECTIVES: This review aimed to evaluate whether the time interval based on AIS onset or ivT time could influence the occurrence of intracranial hemorrhage (ICH) related to ivT and if the circadian rhythm of endogenous production of tissue plasminogen activator (t-PA) favors ICH occurrence. METHODS: We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase for articles in English using the keywords: 'stroke', 'thrombolysis', and 'circadian'. Articles investigating the AIS onset or ivT time effects on circadian variations of ICH in AIS adult patients treated with ivT were included. Based on ICH's incidence and odds ratio, time intervals associated with higher risk and time intervals associated with lower risk were defined. The Newcastle-Ottawa Scale was used to assess the risk of bias. The resulting data were reported in a qualitative narrative synthesis. RESULTS: From the 70 abstracts returned by electronic literature search, six studies with 33,365 patients fulfilled the inclusion criteria, out of which three were retrospective analysis studies, one case-control study, one prospective study, and one post hoc analysis of a multicentre trial. Some studies assessed the relationship between ICH occurrence and circadian rhythm depending on AIS onset time (n = 2), treatment time (n = 2), or both (n = 4). All studies investigated the patients' comorbidities as confounding variables for the circadian pattern of symptomatic ICH (sICH). Two studies found no association between AIS onset or ivT time and patient risk factors, but the other four found several differences and used multivariate logistic regression models to balance these covariates. The overall score of the Newcastle- Ottawa scale was 83.3%, which might be interpreted as overall high quality. CONCLUSION: ICH occurred after ivT seems to follow a circadian pattern; the 18:00-00:00 time frame was the safest one, and patients with AIS onset or ivT time between these hours had the lowest incidence of any ICH, including sICH. The 06:00-12:00 block was associated with the highest incidence of ICH and sICH. However, the analysis is limited by the small number of included studies and the heterogeneous findings reported. Further homogenized studies using comparable time frames and sICH definitions are needed to demonstrate this circadian pattern. The review protocol was registered in the OSF database under reference UHNF, doi:10.17605/OSF.IO/UHNF6.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.040 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.006 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".