Analysis by categorizing or dichotomizing continuous variables is inadvisable: an example from the natural history of unruptured aneurysms.
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ABSTRACT:
SUBMITTER: Naggara O
PROVIDER: S-EPMC8013096 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Importance:Unruptured intracranial aneurysms (UIAs) are relatively common in the general population and are being increasingly diagnosed; a significant proportion are tiny (≤3 mm) aneurysms. There is significant heterogeneity in practice and lack of clear guidelines on the management of incidental, tiny UIAs. It is important to quantify the implications of different management strategies in terms of health benefits to patients. Objective:To evaluate the effectiveness of routine treatment (aneurysm coiling) vs 3 strategies for imaging surveillance compared with no preventive treatment or routine follow-up of tiny UIAs. Design, Setting, and Participants:A decision-analytic model-based comparative effectiveness analysis was conducted from May 1 to June 30, 2017, using inputs from the medical literature. PubMed searches were performed to identify relevant literature for all key model inputs, each of which was derived from the clinical study with the most robust data and greatest applicability. Analysis included 10 000 iterations simulating adult patients with incidental detections of UIAs 3 mm or smaller and no history of subarachnoid hemorrhage. Interventions:The following 5 management strategies for tiny UIAs were evaluated: annual magnetic resonance angiography (MRA) screening, biennial MRA screening, MRA screening every 5 years, aneurysm coiling and follow-up, and no treatment or preventive follow-up. Main Outcomes and Measures:A Markov decision model for lifetime rupture was constructed from a societal perspective per 10 000 patients with incidental, tiny UIAs. Outcomes were assessed in terms of quality-adjusted life-years. Probabilistic, 1-way, and 2-way sensitivity analyses were performed. Results:In this analysis of 10 000 iterations simulating adult patients with a mean age of 50 years, the base-case calculation shows that the management strategy of no treatment or preventive follow-up has the highest health benefit (mean [SD] quality-adjusted life-years, 19.40 [0.31]). Among the management strategies that incorporate follow-up imaging, MRA every 5 years is the best strategy with the next highest effectiveness (mean [SD] quality-adjusted life-years, 18.05 [0.62]). The conclusion remains robust in probabilistic and 1-way sensitivity analyses. No routine follow-up remains the optimal strategy when the annual growth rate and risk of rupture of growing aneurysms are varied. When the annual risk of rupture of nongrowing UIAs is less than 1.7% (0.23% in base case scenario), no follow-up is the optimal strategy. If annual risk of rupture is more than 1.7%, coiling should be performed directly. Conclusions and Relevance:Given the current literature, no preventive treatment or imaging follow-up is the most effective strategy in patients with aneurysms that are 3 mm or smaller, resulting in better health outcomes. More aggressive imaging surveillance for aneurysm growth or preventive treatment should be reserved for patients with a high risk of rupture. Given these findings, it is important to critically evaluate the appropriateness of current clinical practices, and potentially determine specific guidelines to reflect the most effective management strategy for patients with incidental, tiny UIAs.
| S-EPMC5833486 | biostudies-literature
Project description:The evolution of imaging techniques and their increased use in clinical practice have led to a higher detection rate of unruptured intracranial aneurysms. The diagnosis of an unruptured intracranial aneurysm is a source of significant stress to the patient because of the concerns for aneurysmal rupture, which is associated with substantial rates of morbidity and mortality. Therefore, it is important that decisions regarding optimum management are made based on the comparison of the risk of aneurysmal rupture with the risk associated with intervention. This review provides a comprehensive overview of the epidemiology, pathophysiology, natural history, clinical presentation, diagnosis, and management options for unruptured intracranial aneurysms based on the current evidence in the literature. Furthermore, the authors discuss the genetic abnormalities associated with intracranial aneurysm and current guidelines for screening in patients with a family history of intracranial aneurysms. Since there is significant controversy in the optimum management of small unruptured intracranial aneurysms, we provided a systematic approach to their management based on patient and aneurysm characteristics as well as the risks and benefits of intervention.
| S-EPMC4471401 | biostudies-other
Project description:BACKGROUND:About 2 million adults in Germany harbor an unruptured intracranial aneurysm (IA). Rupture can lead to a life-threatening subarachnoid hemorrhage. If an IA is detected incidentally in cranial imaging, it must be decided how to proceed. METHODS:This review includes key publications that were identified by a selective search in the PubMed database using the search term "unruptured intracranial aneurysms," which was performed in July 2019, and based on information obtained from the German Federal Statistical Office on the frequency of the hospital discharge diagnosis "cerebral aneurysm," excluding the diagnosis "subarachnoid hemorrhage," in Germany from 2005 to 2017. RESULTS:The number of patients in Germany who were admitted or treated for an unruptured IA increased by a factor of 2.3 from 2005 to 2017. The average 5-year rupture risk of approximately 3% must be weighed against the approximately 4% risk associated with an endovascular or microneurosurgical treatment. This emphasizes the need for more precise data on the risk of rupture and for algorithms enabling individualized decision-making for patients with unruptured IA. Risk factors such as IA morphology, arterial hypertension, active smoking, and alcohol consumption (>150 g/week) can markedly increase the risk of rupture, which is generally relatively low. Growing aneurysms are 12 times more likely to rupture than stable ones. Follow-up imaging is thus essential whenever observation rather than intervention is chosen as the initial management. CONCLUSION:Patients with unruptured IA should be massessed and managed individually. It is also important that risk factors should be treated, if present. Eligible patients are currently being recruited for a phase III clinical trial on the efficacy of blood pressure reduction combined with acetylsalicylic acid intake to counteract inflammatory processes in the arterial wall.
| S-EPMC7264289 | biostudies-literature
Project description:Background:Cardiovascular complications account for a significant proportion of the shortened lifespan of Marfan syndrome (MFS) patients, with aortic dissection being the most dreadful complication. The aortic root dilates initially in MFS patients, and given its important hemodynamic role, this can lead to aortic regurgitation and poses a substantial risk of aortic dissection. This study seeks to evaluate the natural history of aortic root aneurysms in MFS patients, with a focus on growth rates and correlation of root diameter with the risk of developing aortic complications. Methods:Seventy-eight patients confirmed to have MFS and aortic root dilatation were retrospectively reviewed, and their aortic root diameters serially analyzed. Annual growth rate estimates and yearly rates of adverse events were computed and correlated with aortic diameter. Results:The mean annual growth rate of the aortic root was estimated to be 0.26±0.05 cm/year (range 0.13 to 0.35 cm). Larger aneurysms grew faster, reaching up to 0.46 cm/year for aneurysms >6 cm. Mean age at onset of aortic dissection was 36±4 years. Annual rates of adverse events (rupture, dissection and death) were obtained using a logistic regression model at sizes 3.5, 4, 4.5, 5, 5.5 and 6 cm. A sharp increase of 23% in the probability of the risk of complications at diameters 5.5 to 6 cm was recognized. Conclusions:Aortic root aneurysms in MFS patients tend to have a faster expansion rate compared to non-MFS individuals, with aortic root diameter having a significant impact on the yearly risk of developing aortic complications.
| S-EPMC5721101 | biostudies-literature
Project description:The primary aim of the present study was to identify differences on the transcription level between ruptured and unruptured intracranial aneurysms as well as normal intracranial arteries in human. Keywords: Expression profiling by array
2010-03-04 | GSE15629 | GEO
Project description:Background and purposeThe authors evaluated the impact of morphologic and hemodynamic factors on multiple intracranial aneurysms and aimed to identify which parameters can be reliable indexes as one aneurysm ruptured, and the others did not.MethodsBetween June 2011 and May 2014, 69 patients harboring multiple intracranial aneurysms (69 ruptured and 86 unruptured) were analyzed from 3D-digital subtraction angiography (DSA) images and computational fluid dynamics (CFD). Morphologic and hemodynamic parameters were evaluated for significance with respect to rupture. Receiver operating characteristic (ROC) analysis identified area under the curve (AUC) and optimal thresholds separating ruptured from unruptured intracranial aneurysms for each parameter. Significant parameters were examined by binary logistic regression analysis to identify independent discriminators.ResultsNine morphologic (size, neck width, surface area, volume, diameter of parent arteries, aspect ratio, size ratio, lateral/bifurcation type and regular/irregular type) and 6 hemodynamic (WSSmean, WSSmin, OSI, LSA, flow stability and flow complexity) parameters achieved statistical significance (p<0.05). Six morphologic (size, surface area, volume, aspect ratio, size ratio and regular/irregular type) and five hemodynamic (WSSmean, WSSmin, LSA, flow stability and flow complexity) parameters had high AUC values (AUC>0.7). By binary logistic regression analysis, large aspect ratio and low WSSmean were the independently significant rupture factors (AUC, 0.924; 95% CI, 0.883-0.965).ConclusionsLarge aspect ratio and low WSSmean were independently associated with the rupture status of multiple intracranial aneurysms.
| S-EPMC4492509 | biostudies-literature
Project description:Background Aspect ratio (AP), daughter artery ratio (DA), and lateral angle ratio (LA) have been reported in middle cerebral artery bifurcation aneurysms to correlate with rupture status. Objective To study the differences in AP, DA, LA, and aneurysm orientation between ruptured and unruptured basilar bifurcation aneurysms. Methods Three-dimensional (3D) angiograms of patients with basilar bifurcation aneurysms were analyzed for AP, DA, and LA. Aneurysm projection was classified as type A if the long axis of aneurysm was along basilar artery and type-B if otherwise. Results Thirty-one ruptured and 17 unruptured aneurysms were analyzed. The APs were significantly different (p = 0.008), 2.63 ± 1.1 for ruptured aneurysms and 1.7 ± 0.55 for unruptured aneurysms. AP ≥ 1.9 correlated with rupture status with 68% sensitivity and 70% specificity. Type-A configuration was significantly associated with ruptured aneurysms with an odds ratio (OR) of 5.9. LAs were 0.9 ± 0.4 and 1.4 ± 0.8 for ruptured and unruptured aneurysms, respectively, and the difference tended to be significant (p = 0.56). DAs were 1.25 ± 0.22 and 1.21 ± 0.19 for ruptured and unruptured aneurysms without any statistical difference. Conclusion AP > 1.9, type-A configuration, and lower LA is associated with ruptured basilar bifurcation aneurysms. DA did not differ between ruptured and unruptured aneurysms.
| S-EPMC3699210 | biostudies-other
Project description:The biological mechanisms by which cerebral aneurysms emerge, enlarge and rupture are not totally understood. In the present study, we analyzed the genome-wide gene expression profile in human intracranial aneurysms using cDNA microarrays.
2011-02-01 | GSE26969 | GEO
Project description:Background and Purpose Aneurysmal subarachnoid hemorrhage, almost always from saccular intracranial aneurysm (sIA), is a devastating form of stroke that affects working age population. Cellular and molecular mechanisms predisposing to the rupture of the sIA wall are largely unknown. Such knowledge would facilitate the design of novel diagnostic tools and therapies for the sIA disease. Methods We compared the whole genome expression profile of eleven ruptured sIA wall samples, resected at a median of 15 hours after rupture, to that of eight unruptured ones. Signaling pathways enriched in the ruptured sIA walls were identified with bioinformatic analyses. Their transcriptional control was predicted in silico by seeking the enrichment of conserved transcription factor binding sites in the promoter regions of differentially expressed genes. Results Overall, 686 genes were significantly upregulated and 740 downregulated in the ruptured sIA walls. Significantly upregulated biological processes included: response to turbulent blood flow; chemotaxis; leukocyte migration; oxidative stress; vascular remodelling; and extracellular matrix degradation. Toll like receptor (TLR) signalling and NF-κB, HIF1A and ETS transcription factor binding sites were significantly enriched among the upregulated genes. Conclusions We identified pathways and candidate genes associated to the rupture of human sIA wall. These results provide a molecular basis analysis (a) to identify rupture-prone sIAs and (b) to prevent their rupture. Novel measures to prevent the rupture of sIA wall may include inhibition of response to turbulent blood flow, leukocyte migration, TLR signalling, or blockade of NF-κB, HIF1A and ETS transcription factors.
2010-12-24 | GSE13353 | GEO
Project description:ObjectivesThe aim of this study was to identify risk factors for rupture of unruptured cerebral aneurysms (UCAs) in elderly Japanese patients aged 70 years or older.MethodsThe participants included all patients 70 years of age or older in 3 prospective studies in Japan (the Unruptured Cerebral Aneurysm Study of Japan [UCAS Japan], UCAS II, and the prospective study at the Jikei University School of Medicine). A total of 1,896 patients aged 70 years or older with 2,227 UCAs were investigated. The median and mean follow-up periods were 990 and 802.7 days, respectively.ResultsThe mean aneurysm size was 6.2 ± 3.9 mm. Sixty-eight patients (3.6%) experienced subarachnoid hemorrhage during the follow-up period. Multivariable analysis per patient revealed that in patients aged 80 years or older (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.16-3.49, p = 0.012), aneurysms 7 mm or larger (HR, 3.08; 95% CI, 1.35-7.03, p = 0.007 for 7-9 mm; HR, 7.82; 95% CI, 3.60-16.98, p < 0.001 for 10-24 mm; and HR, 43.31; 95% CI, 12.55-149.42, p < 0.001 for ≥25 mm) and internal carotid-posterior communicating artery aneurysms (HR, 2.45; 95% CI, 1.23-4.88, p = 0.011) were independent predictors for UCA rupture in elderly patients.ConclusionsIn our pooled analysis of prospective cohorts in Japan, patient age and aneurysm size and location were significant risk factors for UCA rupture in elderly patients.
| S-EPMC4662696 | biostudies-literature