Serial Quality of Life Assessment around Screening for Familial Intracranial Aneurysms: A Prospective Cohort Study

Introduction: Screening for intracranial aneurysms (IAs) is cost-effective in first-degree relatives of aneurysmal subarachnoid haemorrhage patients, but its psychosocial impact is largely unknown. Patients and Methods: A consecutive series of persons aged 20–70 years visiting the University Medical Centre Utrecht for first screening for familial IA was approached between 2017 and 2020. E-questionnaires were administered at six time points, consisting of the EQ-5D for health-related quality of life (QoL), HADS for emotional functioning, and USER-P for social participation. QoL outcomes were compared with the general population and between participants with a positive and negative screening for IA. Predictors of QoL outcomes were assessed with linear mixed effects models. Results: 105 participants from 75 families were included; in 10 (10%), an IA was found. During the first year after screening, we found no negative effect on QoL, except for a temporary decrease in QoL 6 months after screening in participants with a positive screen (EQ-5D −11.3 [95% CI: −21.7 to −0.8]). Factors associated with worse QoL were psychiatric disease (EQ-5D −10.3 [95% CI: −15.1 to −5.6]), physical complaints affecting mood (EQ-5D −8.1 [95% CI: −11.7 to −4.4]), and a passive coping style (EQ-5D decrease per point increase on the Utrecht Coping List −1.1 [95% CI: −1.5 to −0.6]). Discussion and Conclusion: We did not find a lasting negative effect on QoL during the first year after screening for familial IA. Predictors for a worse QoL were psychiatric disease, physical complaints affecting mood, and a passive coping style. This information can be used in counselling about familial IA screening

Additional Relevant Intracranial Findings in Persons Screened with MR for Intracranial Aneurysms

BACKGROUND: Radiological screening for intracranial aneurysms (IAs) may identify other relevant intracranial findings. We investigated their prevalence on MR in persons screened for IAs. METHODS: We included all persons who were screened for the presence of IAs with brain MRI/MRA between 1996 and 2022 because of a family history of aneurysmal subarachnoid haemorrhage (aSAH) or autosomal dominant polycystic kidney disease (ADPKD). We reviewed radiology reports of initial and repeated brain MR to identify additional intracranial findings that needed follow-up or treatment, or carried a risk of becoming symptomatic. RESULTS: We included 766 persons (positive family history of aSAH: n = 681; ADPKD: n = 85) who had 1446 MRI/MRAs. At initial screening, 49 additional relevant intracranial findings were reported in 47 persons (6.1%, 95% CI 4.7-8.1%). Of all included persons, 338 (44%) underwent one (n = 154) or more (n = 184) follow-up screenings (total MRI/MRAs at follow-up: n = 680). In 15/338 persons (4.4%, 95% CI 2.7-7.2%), 16 new additional relevant findings were reported at a median follow-up duration of 10 years (IQR 5-12). CONCLUSIONS: Persons who are counselled for screening for IAs should be informed that there is a six percent chance of identifying an additional finding that requires follow-up or treatment, or may become symptomatic. Additionally, after 10-year follow-up screening there is a four percent chance of identifying a new additional relevant finding. The impact of such findings on quality of life needs further study

Screening for intracranial aneurysms in persons ⩾35 years with hypertension and atherosclerotic disease who smoke(d)

Introduction: Lifetime risk of aneurysmal subarachnoid haemorrhage (aSAH) is high (7%) in persons ⩾35 years with hypertension who smoke(d). Whether screening for intracranial aneurysms (IAs) to prevent aSAH is effective in these patients is unknown. Patients and methods: Participants were retrieved from a cohort of patients with clinically manifest atherosclerotic vascular disease included between 2012 and 2019 at the University Medical Centre Utrecht (SMART-ORACLE, NCT01932671) in whom CT-angiography (CTA) of intracranial arteries was performed. We selected patients ⩾35 years with hypertension who smoke(d). CTAs were reviewed for the presence of IAs by experienced neuroradiologists. Patients with IAs were offered follow-up imaging to detect aneurysmal growth. We determined aneurysm prevalence and developed a diagnostic model for IA risk at screening using multivariable logistic regression. Results: IA were found in 25 of 500 patients (5.0% prevalence, 95%CI: 3.3%–7.3%). Median 5 year risk of rupture assessed with the PHASES score was 0.9% (IQR: 0.7%–1.3%). During a median follow-up of 57 months (IQR: 39–83 months) no patients suffered from aSAH. Aneurysmal growth was detected in one patient for whom preventive treatment was advised. IA risk at screening ranged between 1.6% and 13.4% with predictors being age, female sex and current smoking. Discussion and conclusion: IA prevalence in persons ⩾35 years with hypertension and atherosclerotic vascular disease who smoke(d) was 5%. Given the very small proportion of IA that needed preventive treatment, we currently do not advise screening for Caucasian persons older than 35 years of age who smoke and have hypertension in general. Whether screening may be effective for certain subgroups (e.g. women older than 50 years of age) or other ethnic populations should be the subject of future studies

Difference in Rupture Risk Between Familial and Sporadic Intracranial Aneurysms An Individual Patient Data Meta-analysis

OBJECTIVE: We combined individual patient data (IPD) from prospective cohorts of patients with unruptured intracranial aneurysms (UIA) to assess to what extent patients with familial UIA have a higher rupture risk than those with sporadic UIA. METHODS: For this IPD meta-analysis we performed an Embase and Pubmed search for studies published up to December 1, 2020. We included studies that 1) had a prospective study design; 2) included 50 or more patients with UIA; 3) studied the natural course of UIA and risk factors for aneurysm rupture including family history for aneurysmal subarachnoid haemorrhage and UIA; and 4) had aneurysm rupture as an outcome. Cohorts with available IPD were included. All studies included patients with newly diagnosed UIA visiting one of the study centers. The primary outcome was aneurysmal rupture. Patients with polycystic kidney disease and moyamoya disease were excluded. We compared rupture rates of familial versus sporadic UIA using a Cox proportional hazard regression model adjusted for the PHASES score and smoking. We performed two analyses: 1. only studies defining first-degree relatives as parents, children, and siblings and 2. all studies, including those in which first-degree relatives are defined as only parents and children, but not siblings. RESULTS: We pooled IPD from eight cohorts with a low and moderate risk of bias. First-degree relatives were defined as parents, siblings and children in six cohorts (29% Dutch, 55% Finnish, 15% Japanese), totalling 2,297 patients (17% familial, 399 patients) with 3,089 UIA and 7,301 person-years follow-up. Rupture occurred in 10 familial patients (rupture rate: 0·89%/person-year; 95% CI:0·45-1·59) and 41 sporadic patients (0·66%/person-year; 95% CI:0·48-0·89); adjusted HR for familial patients 2·56 (95% CI: 1·18-5·56). After adding also the two cohorts excluding siblings as first-degree relatives resulting in 9,511 patients the adjusted HR was 1·44 (95% CI: 0·86-2·40). CONCLUSION: The risk of rupture of UIA is two and a half times higher, with a range from a 1.2 to 5 times higher risk, in familial than in sporadic UIA. When assessing the risk of rupture in UIA, family history should be taken into account

Sex Difference and Rupture Rate of Intracranial Aneurysms : An Individual Patient Data Meta-Analysis

Background and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. Methods: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. Results: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (>= 7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). Conclusions: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.Peer reviewe

Drivers of healthcare costs in patients with ischaemic stroke: a hospital-based retrospective cohort study

OBJECTIVES: To evaluate how costs of healthcare can be reduced, there is an increasing need to gain insight into the main drivers of such costs. We evaluated drivers of costs of predefined subgroups of patients who had a stroke by linking cost registration with clinical data. METHODS: We retrospectively selected 555 consecutive patients with ischaemic stroke participating between June 2011 and December 2016 in the Dutch Parelsnoer Initiative. Patient characteristics and costs of healthcare activities during hospital admission and the first 3 months after discharge were linked. Patients were divided in subgroups based on age, severity of stroke, stroke subtype, discharge destination and functional outcome. Unit cost per healthcare activity was based on 2018 rates for mutual service in euros. Mean total costs per subgroup were calculated. Multivariate analysis was performed to identify factors associated with costs. RESULTS: Number of admitted days was the main driver of total hospital costs (range 82%-93%) in all predefined subgroups of patients. Second driver was radiological diagnostic investigations (range 2%-9%). Highest costs were observed in patients with a younger age at the time of admission, a higher modified Rankin Scale at the time of discharge and a nursing home as discharge destination. The distribution of costs over the different healthcare activities was associated with stroke subtype; for example, in patients with a cardiac embolism most costs were spent on cardiology-related healthcare activities. CONCLUSION: The number of admitted days was the most important driver of costs in all subgroups of patients with ischaemic stroke. This implicates that to reduce healthcare costs for patients who had a stroke, focus should be on reducing length of hospital stay

Comparison of Rupture Risk of Intracranial Aneurysms Between Familial and Sporadic Patients

Background and Purpose A much higher rupture rate for patients with familial intracranial aneurysms (IA) compared with patients with sporadic IA has been reported in a study with highly selected familial aneurysms using sporadic patients from other populations a controls. We aimed to validate these findings in a large independent series of Dutch patients with familial and sporadic IA. Methods We conducted a secondary analysis of our institutional cohort of patients who were screened for IAs between 1994 and 2016. We assessed the incidence of aneurysmal subarachnoid hemorrhage between familial, defined as ≥2 affected first-degree relatives with aneurysmal subarachnoid hemorrhage and unruptured IA (UIA), and sporadic patients with UIA with Cox regression analysis. Results We identified 62 familial IA patients with 91 UIA and 412 sporadic IA patients with 542 UIA. Despite familial aneurysms being smaller and more often located at low risk sites than sporadic IA, 3 familial patients had aneurysmal subarachnoid hemorrhage (0.77 ruptures per 100 aneurysm-years [95% CI, 0.20-2.09]) compared with 7 sporadic patients (0.51 ruptures per 100 aneurysm-years [95% CI, 0.22-1.01]). As compared to sporadic UIA, familial UIA seems to have a 3-fold higher risk of rupture (hazard ratio, 2.9 [95% CI, 0.6-14]). Conclusions Our results suggest a slightly increased risk of aneurysm rupture for familial compared with sporadic IA, although we were not able to demonstrate this with statistical significance. However, the rupture risk seems less strongly increased than found in a previous study. Based on our results, we recommend to treat familial UIA more aggressively

Difference in aneurysm characteristics between patients with familial and sporadic aneurysmal subarachnoid haemorrhage

Object Patients with familial intracranial aneurysms (IA) have a higher risk of rupture than patients with sporadic IA. We compared geometric and morphological risk factors for aneurysmal rupture between patients with familial and sporadic aneurysmal subarachnoid hemorrhage (aSAH) to analyse if these risk factors contribute to the increased rupture rate of familial IA. Methods Geometric and morphological aneurysm characteristics were studied on CT-angiography in a prospectively collected series of patients with familial and sporadic aSAH, admitted between September 2006 and September 2009, and additional patients with familial aSAH retrieved from the prospectively collected database of familial IA patients of our center. Odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were calculated to compare the aneurysm characteristics between patients with familial and sporadic aSAH. Results We studied 67 patients with familial and 184 with sporadic aSAH. OR's for familial compared with sporadic aSAH were for oval shape 1.16(95%CI:0.65-2.09), oblong shape 0.26 (95%CI:0.03-2.13), irregular shape 0.83(95%CI:0.47-1.49), aspect ratio ≥ 1.6 0.94(95% CI:0.54-1.66), contact with the perianeurysmal environment (PAE) 1.15(95%CI:0.56-2.40), deformation by the PAE 1.05(95%CI:0.47-2.35) and for dominance of the posterior communicating artery (PCoA) in case of PCoA aneurysms 1.97(95% CI:0.50-7.83). Conclusions The geometric and morphological risk factors for aneurysm rupture do not have a higher prevalence in familial than in sporadic aSAH and thus do not explain the increased risk of IA rupture in patients with familial IA. We recommend further search for other potential risk factors for rupture of familial IA, such as genetic factors

The Dutch Parelsnoer Institute Cerebrovascular Disease Initiative : A retrospective study of the effects of integrating clinical care and research on costs and quality of care in patients with ischaemic stroke

INTRODUCTION: The Dutch Parelsnoer Institute (PSI) is a collaboration between all university medical centres in which clinical data, imaging and biomaterials are prospectively and uniformly collected for research purposes. The PSI has the ambition to integrate data collected in the context of clinical care with data collected primarily for research purposes. We aimed to evaluate the effects of such integrated registration on costs, efficiency and quality of care. METHODS: We retrospectively included patients with cerebral ischaemia of the PSI Cerebrovascular Disease Consortium at two participating centres, one applying an integrated approach on registration of clinical and research data and another with a separate method of registration. We determined the effect of integrated registration on (1) costs and time efficiency using a comparative matched cohort study in 40 patients and (2) quality of the discharge letter in a retrospective cohort study of 400 patients. RESULTS: A shorter registration time (mean difference of -4.6 min, SD 4.7, p=0.001) and a higher quality score of discharge letters (mean difference of 856 points, SD 40.8, p<0.001) was shown for integrated registration compared with separate registration. Integrated registration of data of 300 patients per year would save around €700 salary costs per year. CONCLUSION: Integrated registration of clinical and research data in patients with cerebral ischaemia is associated with some decrease in salary costs, while at the same time, increased time efficiency and quality of the discharge letter are accomplished. Thus, we recommend integrated registration of clinical and research data in centres with high-volume registration only, due to the initial investments needed to adopt the registration software

Difference in aneurysm characteristics between patients with familial and sporadic aneurysmal subarachnoid haemorrhage

Object Patients with familial intracranial aneurysms (IA) have a higher risk of rupture than patients with sporadic IA. We compared geometric and morphological risk factors for aneurysmal rupture between patients with familial and sporadic aneurysmal subarachnoid hemorrhage (aSAH) to analyse if these risk factors contribute to the increased rupture rate of familial IA. Methods Geometric and morphological aneurysm characteristics were studied on CT-angiography in a prospectively collected series of patients with familial and sporadic aSAH, admitted between September 2006 and September 2009, and additional patients with familial aSAH retrieved from the prospectively collected database of familial IA patients of our center. Odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were calculated to compare the aneurysm characteristics between patients with familial and sporadic aSAH. Results We studied 67 patients with familial and 184 with sporadic aSAH. OR's for familial compared with sporadic aSAH were for oval shape 1.16(95%CI:0.65-2.09), oblong shape 0.26 (95%CI:0.03-2.13), irregular shape 0.83(95%CI:0.47-1.49), aspect ratio ≥ 1.6 0.94(95% CI:0.54-1.66), contact with the perianeurysmal environment (PAE) 1.15(95%CI:0.56-2.40), deformation by the PAE 1.05(95%CI:0.47-2.35) and for dominance of the posterior communicating artery (PCoA) in case of PCoA aneurysms 1.97(95% CI:0.50-7.83). Conclusions The geometric and morphological risk factors for aneurysm rupture do not have a higher prevalence in familial than in sporadic aSAH and thus do not explain the increased risk of IA rupture in patients with familial IA. We recommend further search for other potential risk factors for rupture of familial IA, such as genetic factors