Jan Holst

Collected world and single center experience with endovascular treatment of ruptured abdominal aortic aneurysms

Background:Case and single center reports have documented the feasibility and suggested the effectiveness of endovascular aneurysm repair (EVAR) of ruptured abdominal aortic aneurysms (RAAAs), but the role and value of such treatment remain controversial. Objective:To clarify these we examined a collected experience with use of EVAR for RAAA treatment from 49 centers. Methods:Data were obtained by questionnaires from these centers, updated from 13 centers committed to EVAR treatment whenever possible and included treatment details from a single center and information on 1037 patients treated by EVAR and 763 patients treated by open repair (OR). Results:Overall 30-day mortality after EVAR in 1037 patients was 21.2%. Centers performing EVAR for RAAAs whenever possible did so in 28% to 79% (mean 49.1%) of their patients, had a 30-day mortality of 19.7% (range: 0%–32%) for 680 EVAR patients and 36.3% (range: 8%–53%) for 763 OR patients (P < 0.0001). Supraceliac aortic balloon control was obtained in 19.1% ± 12.0% (±SD) of 680 EVAR patients. Abdominal compartment syndrome was treated by some form of decompression in 12.2% ± 8.3% (±SD) of these EVAR patients. Conclusion:These results indicate that EVAR has a lower procedural mortality at 30 days than OR in at least some patients and that EVAR is better than OR for treating RAAA patients provided they have favorable anatomy; adequate skills, facilities, and protocols are available; and optimal strategies, techniques, and adjuncts are employed.

Protamine neutralization of intravenous and subcutaneous low-molecular-weight heparin (tinzaparin, Logiparin). An experimental investigation in healthy volunteers.

The aim of the present study was to investigate whether tinzaparin sodium (a low-molecular-weight heparin (LMWH)) was fully and permanently neutralized in vivo in man by protamine sulphate (PS) after intravenous (i.v.) or subcutaneous (s.c.) injection. Fifty healthy adults equally divided in five age- and sex-matched groups were included. The groups received 50 IU unfractionated heparin (UH)/kg body weight (b.w.) i.v., 50 anti-factor Xa (anti-Xa) IU tinzaparin/kg b.w. i.v., 75 anti-Xa IU tinzaparin/kg b.w. s.c, 175 anti-Xa IU tinzaparin/kg b.w. s.c, or 1 ml of saline s.c PS was given as a 10 min infusion in a dose of 1 mg/100 IU of heparin in the four first groups while 0 .5 mg PS/kg b.w. was given in the placebo group. In the i.v. groups PS was administered 45 min after the heparin injection, and in the s.c. groups 180 min post-heparin injection. In the UH group PS fully and permanently neutralized all three activities. In the i.v. tinzaparin group PS reversed 80% of the anti-Xa activity, while the anti-IIa and aPTT activities were fully reversed. A slight, but statistically significant, increase in anti-Xa and anti-IIa activities were seen following i.v. tinzaparin. In the s.c. groups 60–65% of the observed peak anti-Xa activity was neutralized, anti-IIa was almost completely reversed, and aPTT returned nearly to baseline values. A gradual return of the anti-Xa activity (65–75%), anti-IIa activity (55%) and aPTT activity (35–45%) was seen in the s.c. groups 3 h after reversal compared with the observed peak values. A continuous absorption of tinzaparin from the s.c. depot is presumably the cause of the returned activity. PS caused an 8–27% transient drop in the platelet count in all groups. This study confirms that the anti-Xa activity following i.v. and s.c. administration of tinzaparin (a LMWH) is only partially neutralizable by protamine. This is not due to insufficient dosages of the antidote, as an excess of protamine could be demonstrated ex vivo immediately after the protamine infusion. The present results suggest that protamine neutralization of tinzaparin given s.c. should be obtained with intermittent injections or continuous infusion.

Outcome of the Swedish Nationwide Abdominal Aortic Aneurysm Screening Program

Background: A general abdominal aortic aneurysm (AAA) screening program, targeting 65-year-old men, has gradually been introduced in Sweden since 2006 and reached nationwide coverage in 2015. The aim of this study was to determine the outcome of this program. Methods: Data on the number of invited and examined men, screening-detected AAAs, AAAs operated on, and surgical outcome were retrieved from all 21 Swedish counties for the years 2006 through 2014. AAA-specific mortality data were retrieved from the Swedish Cause of Death Registry. A linear regression analysis was used to estimate the effect on AAA-specific mortality among all men ≥65 years of age for the observed time period. The long-term effects were projected by using a validated Markov model. Results: Of 302 957 men aged 65 years invited, 84% attended. The prevalence of screening-detected AAA was 1.5%. After a mean of 4.5 years, 29% of patients with AAA had been operated on, with a 30-day mortality rate of 0.9% (1.3% after open repair and 0.3% after endovascular repair, P<0.001). The introduction of screening was associated with a significant reduction in AAA-specific mortality (mean, 4.0% per year of screening, P=0.020). The number needed to screen and the number needed to operate on to prevent 1 premature death were 667 and 1.5, respectively. With a total population of 9.5 million, the Swedish national AAA-screening program was predicted to annually prevent 90 premature deaths from AAA and to gain 577 quality-adjusted life-years. The incremental cost-efficiency ratio was estimated to be &OV0556;7770 per quality-adjusted life-years. Conclusions: Screening 65-year-old men for AAA is an effective preventive health measure and is highly cost-effective in a contemporary setting. These findings confirm the results from earlier randomized controlled trials and model studies in a large population-based setting of the importance for future healthcare decision making.

The importance of socioeconomic factors for compliance and outcome at screening for abdominal aortic aneurysm in 65-year-old men

OBJECTIVE To evaluate compliance with screening and prevalence of abdominal aortic aneurysm (AAA) in relation to background data regarding area-based socioeconomic status. METHODS Our department annually invites 4300 65-year-old men from the city of Malmö and 15 neighboring municipalities to ultrasound AAA screening. In a cross-sectional cohort study, compliance and AAA prevalence among 8269 men were related to background socioeconomic data such as mean income, proportion of immigrants, percentage of subjects on welfare, smoking habits, and unemployment rate in the different municipalities. The 10 different administrative areas in Malmö were evaluated separately. RESULTS Compliance with screening in the entire area was 6630/8269 (80.2%) but varied between 64.4% and 89.3% in different municipalities (P < .001). In univariate analysis, compliance increased with increasing mean income (r = 0.873; P < .001) but decreased with increasing proportion of immigrants (r = -0.685; P =.005) and subjects on welfare (r = -0.698; P = .004). Compliance in 10 different administrative parts of Malmö (P = .002) also increased with increasing mean income (r = 0.948; P < .001), and decreased with increasing proportion of immigrants (r = -0.650; P = .042) and increasing unemployment rate (r = -0.796; P = .006). Altogether, 117 (1.8%) AAAs were found, the prevalence differing between both different municipalities (P =.003) and the 10 different administrative parts of Malmö (P =.02). The prevalence of AAA in the 10 administrative parts of Malmö increased with increasing percentage of smokers (r = 0.784; P = .007), percentage of immigrants (r = 0.644; P = .044), and unemployment rate (r = 0.783; P =.007) but decreased with increasing mean income (r = -0.754; P = .012). CONCLUSIONS Compliance with ultrasound screening for AAA differed between different geographical areas. In areas with low socioeconomic status, compliance rates were lower, whereas AAA prevalence was higher. The identification of contextual factors associated with low compliance is important to be able to allow targeted actions to increase efficacy of ultrasound screening for AAA. Targeted actions to increase compliance in those areas are being scientifically investigated and implemented.

Sequential calibration of options

Robust calibration of option valuation models to quoted option prices is non-trivial but crucial for good performance. A framework based on the state-space formulation of the option valuation model is introduced. Non-linear (Kalman) filters are needed to do inference since the models have latent variables (e.g. volatility). The statistical framework is made adaptive by introducing stochastic dynamics for the parameters. This allows the parameters to change over time, while treating the measurement noise in a statistically consistent way and using all data efficiently. The performance and computational efficiency of standard and iterated extended Kalman filters (EKF and IEKF) are investigated. These methods are compared to common calibration such as weighted least squares (WLS) and penalized weighted least squares (PWLS). A simulation study, using the Bates model, shows that the adaptive framework is capable of tracking time varying parameters and latent processes such as stochastic volatility processes. It is found that the filter estimates are the most accurate, followed by the PWLS estimates. The estimates from all of the advanced methods are significantly closer to the true parameters than the WLS estimates which overfits data. The filters are also faster than least squares methods. All calibration methods are also applied to daily European option data on the S&P 500 index, where the Heston, Bates and NIG-CIR models are considered. The results are similar to the simulation study and it can be seen that the overfitting is a real problem for the WLS estimator when applied complex models.

Analysis of approximations of dual control

The dual control problem for time-varying or non-linear systems is inherently analytically and computationally untractable due to the demand of alternating minimizations and mean value computations. Hence, it has to be approached using approximations leading to suboptimal dual control. The core of the successful approximative controller is its ability to be able to consider future changes in the development of the parameters. This paper presents an analysis of the dual-control concept, and a comparison between a number of suboptimal controllers. The analytical comparisons are based on a reformulation of the dual-control problem. The reformulation makes it possible to interpret and understand the nature of the different approximations to dual control, in particular the Adaptive Predictive Controller (APC) and the Active Suboptimal Dual Controller (ASOD). Furthermore, it makes the origin of the computational problems encountered more clear, and suggests new alternatives for approximation. The analysis is carried through on relatively simple examples and is illustrated with simulations. The performance of the controllers when applied to more complicated time-varying systems is illustrated with simulations as well. (Less)

Antithrombotic Properties of a Truncated Recombinant Tissue Factor Pathway Inhibitor in an Experimental Venous Thrombosis Model

The aim of this study was to investigate whether a truncated recombinant tissue factor pathway inhibitor (rTFPI1-161) had an antithrombotic effect comparable to low-molecular-weight (LMW) heparin. A randomized double-dummy study was conducted with 40 rabbits in 6 groups. An experimental thrombosis was induced in the jugular veins by a combination of destroyed endothelium and restricted blood flow. Group 1 was given placebo; group 2, LMW heparin 60 anti-factor Xa units/kg; group 3, rTFPI1-161 0.1 mg/kg; group 4, rTFPI1-161 1.0 mg/kg and group 5, rTFPI1-161 10.0 mg/kg. rTFPI1-161 reduced the thrombus weights in all treated groups, with a significant effect in doses between 1.0 and 10.0 mg/kg compared to placebo. The frequency of thrombosis was significantly reduced in all treated groups. No hemorrhagic side effects were noted. In conclusion, rTFPI1-161 (1.0-10.0 mg/kg) has an antithrombotic effect comparable to that of LMW heparin.

Linear Design of a Nonlinear Observer for Perspective Systems

Estimation of three-dimensional information from two-dimensional images is an important requirement in many computer vision applications. The estimation task can often be formulated as a problem of estimating states and/or parameters in nonlinear dynamic systems. This paper presents an algorithm for recursive state estimation in nonlinear dynamic systems, where the estimated states correspond to three-dimensional positions of feature points on an observed object. The algorithm is designed as a nonlinear observer, with a gain matrix that can be determined using methods from linear control theory. A stability criterion for the resulting nonlinear system is derived, and simulations are presented in order to illustrate the estimation performance.

Topical Haemostatics in Renal Trauma—An Evaluation of Four Different Substances in an Experimental Setting

BACKGROUND Damage control is valuable in hemodynamically unstable trauma patients. To improve the hemostasis of packing, topical hemostatic agents have been suggested. The effects of such agents are unclear in trauma situations. The purpose of this study was to investigate the hemostatic capacity, and the stability of the hemostatic clot, of four substances with different mode of action in an experimental traumatic bleeding model. METHODS A standardized heminefrectomy was performed in 180 heparinized and normotensive Sprauge-Dawley rats. Four different substances were studied (separately and in combinations) in a randomized fashion: gelatin (sponge and matrix), bovine thrombin, freeze-dried recombinant factor VIIa (rFVIIa), and microporous polysaccharide hemospheres. Eight treatment groups (15 animals/group) were considered, primary endpoint was hemostasis within 20 minutes of observation. The effective treatment groups were evaluated in a second set in the same experimental model, but with a prolonged observation time after hemostasis (60 minutes) to control the stability of the clot. RESULTS Those animals treated with gelatin in the comparative study, with and without thrombin or rFVIIa, obtained hemostasis. Thrombin and rFVIIa alone did not have any hemostatic capacity. Only 20% to 25% of the animals obtained hemostasis with microporous polysaccharide hemospheres alone or in combination with rFVIIa. In the prolonged observation study, gelatin alone and in combination with thrombin or rFVIIa was studied. On average, 34% (20%-54%) of the animals rebled with no significant difference between the treatment groups. CONCLUSIONS Gelatin-containing products provided a fast hemostasis in this experimental model. One third of the animals rebled, regardless of whether thrombin or rFVIIa was added. Further studies are demanded to confirm these results clinically.

Early and intermediate outcome of emergency endovascular aneurysm repair of ruptured infrarenal aortic aneurysm: a single-centre experience of 90 consecutive patients.

OBJECTIVE To evaluate the early and intermediate outcome of a consecutive series of emergency endovascular aneurysm repairs (eEVAR) of computed tomography (CT)-verified infrarenal ruptured abdominal aortic aneurysm (rAAA) at a single tertiary referral centre. METHODS Prospectively collected data of patients operated between April 2000 and October 2007 were retrospectively reviewed and all their pre-, intra- and postoperative imaging were re-evaluated. Patient and procedural data were analysed using a Cox multiregression model. RESULTS Ninety patients (86% men, aged 76 (+/-7) years), were identified and included in the analysis. Symptom duration was <3h in 22% of patients, 3-24h in 39% and >24h in 39%. Mean aneurysmal diameter was 73 (+/-14)mm. All patients were treated with the COOK Zenith stent-graft (56% bi-iliac and 44% uni-iliac). Sixty-one percent were haemodynamically unstable on presentation, and 26% required an intra-operative aortic occlusion balloon to maintain haemodynamic stability. The 30-day and 1-year mortality rates were 27% and 37%, respectively. One-year aneurysm-related mortality was 33%. Twenty-eight percent of patients required re-interventions during the follow-up. The use of an aortic occlusion balloon and the presence of cerebrovascular disease or obstructive lung disorder correlated significantly with 30-day mortality in the multivariate analysis. CONCLUSION EVAR is a valid treatment option for rAAA when used as a first-line method for all patients.