Pinar Ulug

Endovascular or open repair strategy for ruptured abdominal aortic aneurysm: 30 day outcomes from IMPROVE randomised trial.

Objective To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. Design Randomised controlled trial. Setting 30 vascular centres (29 UK, 1 Canadian), 2009-13. Participants 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. Interventions 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). Main outcome measures 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. Results 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420;

Observations from the IMPROVE trial concerning the clinical care of patients with ruptured abdominal aortic aneurysm

1939) (95% confidence interval −£625 to £2997). Conclusions A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women. Trial registration Current Controlled Trials ISRCTN48334791.OBJECTIVE To assess whether a strategy of endovascular repair (if aortic morphology is suitable, open repair if not) versus open repair reduces early mortality for patients with suspected ruptured abdominal aortic aneurysm. DESIGN Randomised controlled trial. SETTING 30 vascular centres (29 UK, 1 Canadian), 2009-13. PARTICIPANTS 613 eligible patients (480 men) with a clinical diagnosis of ruptured aneurysm. INTERVENTIONS 316 patients were randomised to the endovascular strategy (275 confirmed ruptures, 174 anatomically suitable for endovascular repair) and 297 to open repair (261 confirmed ruptures). MAIN OUTCOME MEASURES 30 day mortality, with 24 hour and in-hospital mortality, costs, and time and place of discharge as secondary outcomes. RESULTS 30 day mortality was 35.4% (112/316) in the endovascular strategy group and 37.4% (111/297) in the open repair group: odds ratio 0.92 (95% confidence interval 0.66 to 1.28; P=0.62); odds ratio after adjustment for age, sex, and Hardman index 0.94 (0.67 to 1.33). Women may benefit more than men (interaction test P=0.02) from the endovascular strategy: odds ratio 0.44 (0.22 to 0.91) versus 1.18 (0.80 to 1.75). 30 day mortality for patients with confirmed rupture was 36.4% (100/275) in the endovascular strategy group and 40.6% (106/261) in the open repair group (P=0.31). More patients in the endovascular strategy than in the open repair group were discharged directly to home (189/201 (94%) v 141/183 (77%); P<0.001). Average 30 day costs were similar between the randomised groups, with an incremental cost saving for the endovascular strategy versus open repair of £1186 (€1420;

Genetic Variation on Chromosome 6 Influences F Cell Levels in Healthy Individuals of African Descent and HbF Levels in Sickle Cell Patients

1939) (95% confidence interval -£625 to £2997). CONCLUSIONS A strategy of endovascular repair was not associated with significant reduction in either 30 day mortality or cost. Longer term cost effectiveness evaluations are needed to assess the full effects of the endovascular strategy in both men and women. TRIAL REGISTRATION Current Controlled Trials ISRCTN48334791.

Ruptured Aneurysm Trials: The Importance of Longer-term Outcomes and Meta-analysis for 1-year Mortality.

Single‐centre series of the management of patients with ruptured abdominal aortic aneurysm (AAA) are usually too small to identify clinical factors that could improve patient outcomes.

Individual-patient meta-analysis of three randomized trials comparing endovascular versus open repair for ruptured abdominal aortic aneurysm

Fetal haemoglobin (HbF) is a major ameliorating factor in sickle cell disease. We investigated if a quantitative trait locus on chromosome 6q23 was significantly associated with HbF and F cell levels in individuals of African descent. Single nucleotide polymorphisms (SNPs) in a 24-kb intergenic region, 33-kb upstream of the HBS1L gene and 80-kb upstream of the MYB gene, were typed in 177 healthy Afro-Caribbean subjects (AC) of approximately 7% European admixture, 631 healthy Afro-Germans (AG, a group of African and German descendents located in rural Jamaica with about 20% European admixture), 87 West African and Afro-Caribbean individuals with sickle cell anaemia (HbSS), as well as 75 Northern Europeans, which served as a contrasting population. Association with a tag SNP for the locus was detected in all four groups (AC, P = 0.005, AG, P = 0.002, HbSS patients, P = 0.019, Europeans, P = 1.5×10−7). The association signal varied across the interval in the African-descended groups, while it is more uniform in Europeans. The 6q QTL for HbF traits is present in populations of African origin and is also acting in sickle cell anaemia patients. We have started to distinguish effects originating from European and African ancestral populations in our admixed study populations.

Meta‐analysis of the current prevalence of screen‐detected abdominal aortic aneurysm in women

OBJECTIVE To assess current knowledge for the management of ruptured abdominal aortic aneurysm (AAA), based on the 1-year outcomes of 3 recent randomised trials. METHODS An individual patient data meta-analysis of three recent randomised trials of endovascular versus open repair, including 817 patients, was conducted according to a pre-specified analysis plan, report all-cause mortality and re-interventions at 1 year after the index event. RESULTS Mortality across the 3 trials at 1-year was 38.6% for the EVAR or endovascular strategy patient groups and 42.8% for the open repair groups, pooled odds ratio 0.84 (95% CI 0.63-1.11), p = .209. There was no evidence of heterogeneity in the odds ratios between trials. When the patients in the endovascular strategy group of the IMPROVE trial were restricted to those with proven rupture who were anatomically suitable for endovascular repair, the pooled odds ratio reduced slightly to 0.80 (95% CI 0.56-1.16), p = .240. CONCLUSIONS After 1 year there is a consistent but non-significant trend for lower mortality for EVAR or an endovascular strategy. Taken together with the recent gains in health economic outcomes demonstrated at 1 year in the IMPROVE trial, the evidence suggests that endovascular repair should be used more widely for ruptured aneurysms.

Association of sickle avascular necrosis with bone morphogenic protein 6

The benefits of endovascular repair of ruptured abdominal aortic aneurysm remain controversial, without any strong evidence about advantages in specific subgroups.

Transfer of patients with ruptured abdominal aortic aneurysm from general hospitals to specialist vascular centres: results of a Delphi consensus study

Although women represent an increasing proportion of those presenting with abdominal aortic aneurysm (AAA) rupture, the current prevalence of AAA in women is unknown. The contemporary population prevalence of screen‐detected AAA in women was investigated by both age and smoking status.

Circulating DNA: a potential marker of sickle cell crisis

Dear Editor, Avascular necrosis (AVN) of femoral and humeral heads is a frequent and debilitating complication in patients with sickle cell disease (SCD), its prevalence being highest in individuals with SCD-Hb SS and coincidental α-thalassemia. Family and sibling studies suggest a genetic predisposition, and recently, variation in genes involved in bone modeling or the vasculature have been proposed as significant factors in the development of AVN [1]. Baldwin et al. [1] investigated single nucleotide polymorphisms (SNPs) in candidate genes involved in vascular function, inflammation, oxidant stress, and endothelial cell biology for association with AVN. SNPs in bone morphogenic protein 6 (BMP6), annexin A2 (ANXA2), and klotho (KL) genes were suggested to be associated with sickle cell AVN. We attempted to replicate this association in 244 adult patients with SCD, 39 of whom had joint symptoms with radiological and/or magnetic resonance imaging (MRI) evidence of AVN (AVN group; cases), whereas the remaining 205 had no clinical symptoms of AVN (nonAVN group; controls). Those with AVN, on average, were 3 years older than the controls (Table 1). In addition, individuals with AVN had a higher prevalence of coincidental α-thalassemia, higher hematocrit levels, and lower fetal hemoglobin (Hb F) levels when compared to the nonAVN group, though these observations were not statistically significant (Table 1). All patients were of West African or African Caribbean descent. The study was approved by the King’s College Hospital Research Ethics Committee (LREC 01-083). Based on the visual inspection of phased haplotypes in the Yoruba population from Ibadan, Nigeria (YRI), two haplotype blocks were defined in KL, one block in ANXA2, and three blocks in BMP6. Tag SNPs with population frequency information were then selected using the HapMap Project data provided for the Yoruba community, as this ethnic group relates most closely to our sample population. Of the selected tag SNPs, one per gene was identical to that used by Baldwin et al. (Table 2). The selected tag SNPs were genotyped using the TaqMan® allelic discrimination assay. Most assays performed well, but ANXA2-2 failed repeatedly. Genotype data generated from the SNP assays for the remaining six markers ranged from 95.2% to 100% complete, and markers displayed no deviation from the Hardy–Weinberg equilibrium. To test for trait association with the candidate SNPs, allele frequencies between cases (AVN group) and controls (non-AVN group) were compared using Pearson’s chisquare statistic with a significance threshold of p≤0.05 (Table 2). Characterization of the six SNP markers revealed that only one (BMP6-3 or rs3812163) showed significant evidence of association (p=0.021) with AVN. Ann Hematol (2009) 88:803–805 DOI 10.1007/s00277-008-0659-5

Hydroxyurea therapy lowers circulating DNA levels in sickle cell anemia

Aim To explore areas of consensus and disagreement concerning the interhospital transfer of patients with a clinical diagnosis of ruptured abdominal aortic aneurysm. Methods A three-round Delphi questionnaire approach was used among vascular and endovascular surgery and emergency medicine specialists to explore patient characteristics and clinical management issues for emergency interhospital transfer. Analysis is based on 38 responses to rounds 2 and 3 (19 vascular surgeons, 6 interventional radiologists, 13 emergency care specialists) with agreement reported when 70% of respondents were in agreement. Results Initially there was agreement that transfer patients should be <85 years of age, either alert or with fluctuating consciousness, with moderate or minimal systemic disease, needing no/some help with daily living. Round 3 clarified that patients requiring inotropes and those institutionalised for mental infirmity should be transferred. Those with cardiac arrest in current episode should not be transferred. There was no agreement as to whether those institutionalised with physical infirmities, unconscious/intubated patients or those with severe systemic disease should be transferred. Speed was accepted as important, with agreement for specialty trainees to arrange transfer if consultants were not on site. Consultant–consultant discussion was recommended for patients with severe systemic disease. CT confirmation of diagnosis was considered unnecessary before transfer but ultrasound assessment was desirable, and transfers should not be delayed by waiting for specific tests. There was no agreement about blood tests and ECG before transfer or whether blood should accompany the patient being transferred. There was no agreement as to whether specific staff/facilities needed to be in place at the specialist hospital. A systolic blood pressure ≥70 mm Hg was sufficient for transfer without the need for intravenous fluids unless deterioration occurred. Conclusions There is broad agreement about the type of patient who should be eligible for transfer but disagreements about patient management before and during transfer remain.