Are there differences in LDL-C target value attainment in Austrian federal states? Yes!

UNLABELLED: Low density lipoprotein (LDL-C) levels determine the cardiovascular risk. Previous studies indicated an LDL-C target attainment of around 50%, but no Austrian wide analysis on results for the federal states was available. We therefore sought to detect potential differences. DESIGN: Open-label, non-interventional, longitudinal study, registered: www.clinicaltrials.gov NCT 01381679. In all, 746 statin treated patients not at LDL-C goal received intensified therapy for 12 months. The sample was split into nine subgroups, representing the federal states of Austria.We detected an east-west gradient for baseline LDL-C. Individual target values were achieved by 37.2% (range: 26.1-57.7%). After 12 months, LDL-C < 70 mg/l was achieved by 13.5% (5.9-38.5%). Univariate ANCOVA retrieved significant differences within the states (Upper Austria and Salzburg, p = 0.001 and p = 0.0015, respectively). Furthermore, the capacity of intensified lipid lowering therapy applied in practice was as high as -42% as compared to previous standard therapy (additional LDL-C reduction after switch from baseline therapy in Vorarlberg).

Can LDL-cholesterol targets be achieved in a population at high risk? Results of the non-interventional study ACT II.

OBJECTIVE: Lowering low-density lipoprotein cholesterol (LDL-C) levels can reduce vascular clinical endpoints in outcome studies. Despite this evidence, previous cross-sectional analyses reported a mean LDL-C target attainment of <50%. This non-interventional, longitudinal study aimed to asses the rate of target attainment by intensified LDL-C lowering therapy in a high-risk population under routine medical care. DESIGN: This was an open-label, non-interventional, observational, non-comparative longitudinal study. METHODS: A total of 1682 outpatients at high cardiovascular risk, not at LDL-C target despite statin therapy, were documented. Treating physicians administered an intensified therapy at their discretion. In all, 794 patients completed all the examinations at baseline after 3 and 12 months. The achieved LDL-C reductions was evaluated based on expert consensus reflecting the 2007 guidelines issued by the European Society of Cardiology (ESC) on cardiovascular disease prevention. REGISTRATION: www.clinicaltrials.gov , identification number NCT 01381679 RESULTS: In the study, 40.3% achieved the individual LDL-C target of <.8 mmol/L (70 mg/dl) or <2.5 mmol/L (100 mg/dl); 73% received a simvastatin/ezetimibe fixed-dose combination; 3% received add-on ezetimibe and 23% statin therapy at maintained or increased doses; 1% received no drug treatment at all. LDL-C declined after 12 months by -31.0% (ratio 0.69, 95% CI 0.67-0.71, p<0.001), triglycerides by -11.8% (ratio 0.88, 95% CI 0.85-0.91, p<0.01) and high-density lipoprotein cholesterol (HDL-C) increased by 11.9% (ratio 1.12, 95% CI 1.10-1.14, p<0.01). CONCLUSION: Intensified therapy was effective, but target attainment was still low at 40.3% or 13.9% with regard to the new 2011 guidelines issued by the European Atherosclerosis Society (EAS) and the ESC on dyslipidemias. Enhanced screening of LDL-C levels and the use of statins at highest tolerated dose and concomitant combination therapy is recommended in order to achieve LDL-C targets outlined by current guidelines. Limitations include the design as a non-interventional study. However, this study reflects real life conditions.

Characteristics of health interventions: a systematic analysis of the Austrian Procedure Catalogue.

The Austrian Procedure Catalogue contains 1,500 codes for health interventions used for performance-oriented hospital financing in Austria. It offers a multiaxial taxonomy. The aim of this study is to identify characteristics of medical procedures. Therefore a definition analysis followed by a typological analysis was conducted. Search strings were generated out of code descriptions regarding the heart, large vessels and cardiovascular system. Their definitions were looked up in the Pschyrembel Clinical Dictionary and documented. Out of these definitions, types which represent characteristics of health interventions were abstracted. The three axes of the Austrian Procedure Catalogue were approved as well as new, relevant information identified. The results are the foundation of a further enhancement of the Austrian Procedure Catalogue.

Early viral load and recipient interleukin-28B rs12979860 genotype are predictors of the progression of hepatitis C after liver transplantation.

There have been few detailed studies of viral kinetics after liver transplantation (LT), and conflicting data have been reported on viral loads and the severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of interleukin-28B (IL-28B) genotypes on patient outcomes and the severity of recurrent HCV disease. The viral loads were measured 2, 4, 12, 24, and 48 weeks after LT, and the recipient/donor IL-28B genotypes of 164 patients were determined. A Cox regression analysis showed that the viral load at week 2 was an independent negative predictor of recipient outcomes. A week 2 viral load ≥ 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years, 21 of 164 patients (12.8%) developed a cholestatic type of HCV recurrence and/or rapidly progressed to cirrhosis within 1 year. A multivariate binary regression analysis showed that HCV viremia at week 2 and a non-C/C recipient IL-28B genotype were independent risk factors for cholestatic recurrent HCV. No predictive factors could be found for the occurrence of recurrent liver cirrhosis 5 and 10 years after LT. Our study shows that the HCV RNA level at week 2 and the recipient IL-28B genotype are independent, statistically significant risk factors for post-LT cholestatic HCV, and it emphasizes the importance of viral load monitoring and IL-28B genotyping for identifying HCV recipients at risk for severe HCV recurrence.

Primary percutaneous intervention of ST-elevation myocardial infarction in Austria: Results from the Austrian acute PCI registry 2005-2007.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) has become the preferred reperfusion strategy in ST-elevation myocardial infarction (STEMI). Implementation of networks of care and registries providing continuous quality assessment are key components for optimal management in patients with STEMI. AIM: To analyze procedural success and in-hospital outcome of interventional therapy of STEMI in Austria. METHODS: We evaluated a total number of 4016 consecutive STEMI patients registered in the first three years after implementation of the Austrian acute PCI registry in January 2005. RESULTS: The rate of PPCI as an indication for acute coronary intervention increased from 83.5% in 2005 to 92.4% in 2007 (P < 0.0001). During this period the median door-to-balloon time decreased from 60.0 (40.0-90.0) min to 53.0 (30.0-80.0) min (P = 0.012). The percentage of patients receiving adequate adjunctive antithrombotic therapy with ASA/heparin and clopidogrel significantly increased (78.8-85.1% and 67.8-90.3%, respectively; P < 0.001). Overall in-hospital mortality was 9.6% in rescue PCI, 6.4% in facilitated PCI and 5.1% in PPCI. On multivariate analysis, cardiogenic shock (OR: 20.21, 95% CI: 12.21-33.44, P < 0.001), resuscitation (OR: 2.62, 95% CI: 1.47-4.69, P = 0.01), age (OR: 1.04, 95% CI: 1.02-1.06, P < 0.001) and angiographic success (OR: 5.93, 95% CI: 3.33-10.57, P < 0.001) were independent predictors of in-hospital death. CONCLUSION: Continuous nationwide efforts to establish regional networks for STEMI treatment in the years 2005-2007 led to a decrease in door-to-balloon time, improved adjunctive antithrombotic therapy and an in-hospital mortality of 5%. Results of interventional STEMI treatment in Austria are in accordance with current guidelines and with other contemporary registries.

Tutorial in medical decision modeling incorporating waiting lines and queues using discrete event simulation.

In most decision-analytic models in health care, it is assumed that there is treatment without delay and availability of all required resources. Therefore, waiting times caused by limited resources and their impact on treatment effects and costs often remain unconsidered. Queuing theory enables mathematical analysis and the derivation of several performance measures of queuing systems. Nevertheless, an analytical approach with closed formulas is not always possible. Therefore, simulation techniques are used to evaluate systems that include queuing or waiting, for example, discrete event simulation. To include queuing in decision-analytic models requires a basic knowledge of queuing theory and of the underlying interrelationships. This tutorial introduces queuing theory. Analysts and decision-makers get an understanding of queue characteristics, modeling features, and its strength. Conceptual issues are covered, but the emphasis is on practical issues like modeling the arrival of patients. The treatment of coronary artery disease with percutaneous coronary intervention including stent placement serves as an illustrative queuing example. Discrete event simulation is applied to explicitly model resource capacities, to incorporate waiting lines and queues in the decision-analytic modeling example.

Regression tree construction by bootstrap: model search for DRG-systems applied to Austrian health-data.

BACKGROUND: DRG-systems are used to allocate resources fairly to hospitals based on their performance. Statistically, this allocation is based on simple rules that can be modeled with regression trees. However, the resulting models often have to be adjusted manually to be medically reasonable and ethical. METHODS: Despite the possibility of manual, performance degenerating adaptations of the original model, alternative trees are systematically searched. The bootstrap-based method bumping is used to build diverse and accurate regression tree models for DRG-systems. A two-step model selection approach is proposed. First, a reasonable model complexity is chosen, based on statistical, medical and economical considerations. Second, a medically meaningful and accurate model is selected. An analysis of 8 data-sets from Austrian DRG-data is conducted and evaluated based on the possibility to produce diverse and accurate models for predefined tree complexities. RESULTS: The best bootstrap-based trees offer increased predictive accuracy compared to the trees built by the CART algorithm. The analysis demonstrates that even for very small tree sizes, diverse models can be constructed being equally or even more accurate than the single model built by the standard CART algorithm. CONCLUSIONS: Bumping is a powerful tool to construct diverse and accurate regression trees, to be used as candidate models for DRG-systems. Furthermore, Bumping and the proposed model selection approach are also applicable to other medical decision and prognosis tasks.

Capacity constraints and cost-effectiveness: a discrete event simulation for drug-eluting stents.

BACKGROUND: Waiting times for access to care, for example, for diagnostic imaging or surgery, are a highly relevant issue in health care. Waiting or deferred treatment caused by limited resource capacities can affect treatment success, quality of life, and costs. However, when treatment alternatives are compared in economic models, often unrestricted availability of resources is assumed, and dynamic changes in waiting lines remain unconsidered. The objective of this study was to evaluate the impact of potential real-world capacity restrictions and implied waiting lines on cost-effectiveness results and additional model outcomes. METHODS: A case study of drug-eluting and bare-metal stent treatment illustrates the effect of hypothetical capacity limitations of daily stenting procedures. Therefore, a decision-analytic model which allows for explicitly defined resource capacities and dynamic waiting lines was built using discrete event simulation. Cost-effectiveness, utilization, waiting time, and budgetary impact of alternative treatment scenarios are analyzed under the assumption of limited and unlimited resource capacities. RESULTS: The compared treatment allocation scenarios in the case study demonstrate that the additional cost for waiting increases the average treatment cost per patient. The different scenarios have different impacts on waiting lines because of the number of repeated interventions. Additionally, this effect leads to changes in cost-effectiveness results for the hypothetical capacity limit. Explicitly modeled capacities allow for further analysis of capacity utilization, waiting lines, and budgetary impact. CONCLUSION: Our model shows that neglected limited capacities can cause wrong cost-effectiveness results. Therefore, capacities should be explicitly included in decision-analytic models if there is evidence of scarcity.

Alendronate in combination with calcium and vitamin D prevents bone loss after orthotopic liver transplantation: a prospective single-center study.

Bone loss is a common complication in patients before and after liver transplantation (LT). The aim of this study was to investigate the efficacy of prophylactic treatment with bisphosphonates after LT in preventing progressive bone loss in LT patients. We included 136 patients with end-stage liver diseases awaiting LT. Bone mineral density (BMD) (by dual X-ray absorptiometry) and markers of bone metabolism were determined before, and 4, 12, 24, 36, and 48 months after LT. All patients received vitamin D and calcium supplementation before and after LT, those with osteopenia or osteoporosis prior to LT were additionally treated with alendronate following LT. Decreased BMD was seen in a high percentage of patients undergoing LT (osteopenia 48.5%, osteoporosis 23.5%). Reduced BMD before LT was not related to gender, underlying liver disease, or Child-Turcotte-Pugh classification. Body mass index (BMI) prior to LT, however, correlated significantly with the fracture risk. Alendronate prevented the ubiquitously observed bone loss after LT in patients with osteoporosis and osteopenia and, in addition, led to an increase in BMD in patients with osteoporosis within 24 months after LT. In conclusion, our study suggests that alendronate is efficacious in preventing the natural course of bone loss associated with LT.

Tumor microcirculation and diffusion predict therapy outcome for primary rectal carcinoma.

PURPOSE: The aim of our study was to correlate perfusion indices and apparent diffusion coefficients with therapy outcome after chemoradiation. METHODS AND MATERIALS: In 34 patients with primary rectal carcinoma (cT3) undergoing preoperative chemoradiation, pretherapeutic perfusion indices and apparent diffusion coefficients were obtained by dynamic or diffusion-weighted magnetic resonance imaging. Therapy response was defined if the pathologic observation revealed no invasion into the perirectal fat after chemoradiation. RESULTS: In 18 patients, a response and in 16, no response was observed. Statistically significant differences were found for the mean perfusion index (p < 0.001; 7.5 +/- 1.5 mL/min/100 g vs. 10.7 +/- 2.7 mL/min/100 g) and for the intratumoral cumulative fraction of pixels with perfusion-indices > 12 mL/min/100 g (p < 0.001, 3.7 +/- 4.0% vs. 24.7 +/- 17.9%). A three-way ANOVA resulted in significant effects for therapy responder/nonresponder (p < 0.001) and for apparent diffusion coefficient and the individual patients. CONCLUSION: Perfusion indices and apparent diffusion coefficients inside the tumor region seem to be of predictive value for therapy outcome of preoperative therapy in patients with primary rectal carcinoma. Higher parameter levels in the nonresponding group could be explained by increased shunt flow or increased angiogenic activity in aggressive tumor cell clusters resulting in reduced nutrients supply and higher fraction of intratumoral necrosis respectively.

Diffusion-weighted magnetic resonance imaging for monitoring diffusion changes in rectal carcinoma during combined, preoperative chemoradiation: preliminary results of a prospective study.

PURPOSE: To evaluate the clinical value of diffusion-weighted magnetic resonance imaging (DW-MRI) to monitor response of primary carcinoma of the rectum to preoperative chemoradiation by measuring tumor apparent diffusion coefficient (ADC). MATERIALS AND METHODS: Diffusion data of nine patients undergoing preoperative combined chemoradiation for clinical staged T3, N(0-2), M(0) carcinoma of the rectum were analyzed. Diffusion-weighted echo-planar MR images were obtained prior to and at specified intervals during chemoradiation and ADCs calculated from acquired tumor images. RESULTS: Comparison of mean ADC and cumulative radiation dose showed a significant decrease of mean ADC at the 2nd (P = 0.028), 3rd (P = 0.012), and 4th (P = 0.008) weeks of treatment. Cytotoxic edema and fibrosis were considered as reasons for ADC decrease. CONCLUSION: This study demonstrated tumor ADC changes via detection of therapy-induced alterations in tumor water mobility. Our results indicate that diffusion-weighted imaging may be a valuable clinical tool to diagnose the early stage of radiation-induced fibrosis.

[Vaccine protection in the elderly: are Austrian seniors adequately protected by vaccinations?]. / Impfschutz im Alter: Sind österreichische Senioren durch Impfungen ausreichend geschützt?

OBJECTIVE: The aim of the study was to evaluate, if elderly persons are sufficiently protected against infectious diseases by vaccination. PROBANDS AND METHODS: 300 elderly (> 60 years) and 300 young (< 35 years) persons from five Austrian cities were recruited according to the criteria of a field study. Antibody concentrations against tetanus, diphtheria, tickborne encephalitis and influenza were assessed by ELISA or by haemagglutination inhibition test. Disease and vaccination histories were recorded. RESULTS: The results of the study demonstrate that protection against infectious diseases was frequently insufficient in the elderly. This was partly due to the fact that old persons were not vaccinated according to recommended strategies. However, low antibody concentration and a short duration of protective humoral immunity were also observed in many elderly persons in spite of regular vaccination. This was not only the case in frail, but also in healthy elderlies. CONCLUSION: The data demonstrate that vaccination has a relatively weak and short-lasting effect in old age. The results of the study should stimulate discussions about strategies how vaccinations can be made more effective in old age. Improved campaigns, shortened vaccination intervals as well as the design of novel vaccines tailored to fulfill the specific demands of the aging immune system are imaginable.