[From Model to Regional Regular Care - Long-Term Effects of a Regional Budget]. / Vom Modell zur Regionalen Regelversorgung.

AIM: Model projects of a regional budget or a model project according to §â€Š64b SGB V have been for more than 18 years. The structural, economic, and therapeutic long-term effects are described in this paper. METHODOLOGY: The model project in the Steinburg district (Schleswig-Holstein) describes the developments between 2002 (index year) and 2020 that have developed through the regional budget. The article describes the situation and its specific changes in the first german model region. There is no comparable control group. RESULTS: In the observed period, the number of people treated was stable within a corridor that has been in the contract with the stakeholders. Care has shifted relevantly from fully inpatient to outpatient and day clinic treatment. The costs have remained stable and thus differ significantly from the overall increase in health care costs. New supply concepts could be implemented. CONCLUSION: The model projects described lead to setting-independent care and are suitable for standard care in a defined region.

Study protocol for a randomised controlled trial evaluating an evidence-based, stepped and coordinated care service model for mental disorders (RECOVER).

INTRODUCTION: Healthcare systems around the world are looking for solutions to the growing problem of mental disorders. RECOVER is the synonym for an evidence-based, stepped and cross-sectoral coordinated care service model for mental disorders. RECOVER implements a cross-sectoral network with managed care, comprehensive psychological, somatic and social diagnostics, crisis resolution and a general structure of four severity levels, each with assigned evidence-based therapy models (eg, assertive community treatment) and therapies (eg, psychotherapy). The study rationale is the investigation of the effectiveness and efficiency of stepped and integrated care in comparison to standard care. METHODS AND ANALYSIS: The trial is conducted in accordance to the Standard Protocol Items: Recommendations for Interventional Trials Statement. The study aims to compare the RECOVER model with treatment as usual (TAU). The following questions are examined: Does RECOVER reduce healthcare costs compared with TAU? Does RECOVER improve patient-relevant outcomes? Is RECOVER cost-effective compared with TAU? A total sample of 890 patients with mental disorders will be assessed at baseline and individually randomised into RECOVER or TAU. Follow-up assessments are conducted after 6 and 12 months. As primary outcomes, cost reduction, improvement in symptoms, daily functioning and quality of life as well as cost-effectiveness ratios will be measured. In addition, several secondary outcomes will be assessed. Primary and secondary outcomes are evaluated according to the intention-to-treat principle. Mixed linear or logistic regression models are used with the direct maximum likelihood estimation procedure which results in unbiassed estimators under the missing-at-random assumption. Costs due to healthcare utilisation and productivity losses are evaluated using difference-in-difference regressions. ETHICS AND DISSEMINATION: Ethical approval from the ethics committee of the Hamburg Medical Association has been obtained (PV5672). The results will be disseminated to service users and their families via the media, to healthcare professionals via professional training and meetings and to researchers via conferences and publications. TRIAL REGISTRATION NUMBER AND REGISTRY NAME: ClinicalTrials.gov (NCT03459664), RECOVER PROTOCOL VERSION: 19 March 2020 (V.3.0).

Costs of regulating ammonia emissions from livestock farms near Natura 2000 areas - analyses of case farms from Germany, Netherlands and Denmark.

Natura 2000 areas are designated according to the EU's Birds and Habitats Directives in order to protect particular habitats and species. A variety of these habitats and species are particularly sensitive to deposition of nitrogen caused by ammonia emissions. Livestock farming is the primary source of this pollution. The purpose of this paper is to compare the costs of reaching the ammonia emission targets for different livestock farms near Natura 2000 sites in the Netherlands, Germany (Schleswig-Holstein), and Denmark. These countries have some of the highest NH3 deposition rates in Europe, and Germany in particular will have to implement new measures to reach the NEC requirements for 2030. This will also benefit nature sites in Denmark as a large share of the ammonia emissions is dispersed over long distances. The general regulation includes implementation of BAT technologies and emission ceilings. The analysis looks at regulatory aspects, the emission requirements and the cost of implementing the technologies to reduce emissions further. The selected case farms are a finisher farm and a dairy farm, and the distance to a Natura 2000 site is 400 and 2000 m. In all three countries, relatively few livestock farms are situated near or inside Natura 2000 areas. The regulatory approach is very different in the three countries and key issues are: additional deposition from projects, neighbouring livestock farms (cumulation), the inclusion of background deposition and the use of the critical loads concept. The Dutch PAS system is interesting as projected reductions in emissions are distributed as additional "room for development" today. The costs for the case farm with finishers in Schleswig-Holstein are the highest as the Filter Decree requires the use of air scrubbers. The findings suggest that farms 400 m from a Natura 2000 site in the Netherlands face lower and less costly constraints than in the other countries, whereas the opposite is the case for farms 2000 m from Natura 2000 sites. The requirements near Natura 2000, where strict requirements apply, are so high that farms will expand at a different site instead.

Coaggregation of Two Anionic Azo Dyestuffs: A Combined Static Light Scattering and Small-Angle X-ray Scattering Study.

The formation of azo dyestuff aggregates in dilute aqueous solution induced by the addition of Mg2+, Ca2+, Sr2+, or Ba2+ ions is followed by time-resolved static light scattering (SLS) and time-resolved small-angle X-ray scattering (SAXS). Time-dependent molar mass data of the growing aggregates is interpreted by means of a kinetic model introduced by Lomakin et al. ( Proc. Natl. Acad. Sci. U.S.A. 1996 , 93 , 1125 ) for the description of ß-amyloid aggregation. This interpretation reveals significant trends within the homologous series of alkaline earth cations. The trends refer to the nucleation and the growth rate of the dyestuff fibers. Time-resolved SAXS experiments indicate that these first two stages are followed by a third one during which a network forms by partial lateral alignment of fibers. At high enough dyestuff concentrations, this network formation even leads to a gel-like phase. Anomalous SAXS (ASAXS) on such a gel phase formed upon the addition of Sr2+ revealed the extent of neutralization of the dyestuff molecules within the gel by the specifically interacting alkaline earth cations.

Long-term comparison of sirolimus-eluting and bare-metal stents in ST-segment elevation myocardial infarction.

OBJECTIVES: We aimed to investigate, in patients with ST-segment elevation myocardial infarction (STEMI), whether the previously reported clinical benefits of sirolimus-eluting stent(s) (SES) in terms of reducing a major adverse cardiac and cerebrovascular event (MACCE) compared with bare-metal stent(s) (BMS) were maintained over a 5-year time period. BACKGROUND: In the prospective single-centre randomized DEBATER trial, SES significantly reduced the rate of MACCE in STEMI patients within 1 year compared with BMS, mainly driven by a reduction of target lesion revascularization. Randomized data on the long-term safety and efficacy of SES in STEMI patients are conflicting and limited. PATIENTS AND METHODS: Between January 2006 and May 2008, a total of 907 STEMI patients were randomized to receive SES or BMS. The primary endpoint was MACCE defined as the composite of death, myocardial infarction, stroke, repeat revascularization and bleeding. Five-year follow-up data were collected by reviewing hospital records, telephone calls and a written questionnaire. RESULTS: At 5 years, the rate of MACCE between the SES group and the BMS group was no longer significantly different (33.3 vs. 39.3%, P=0.12). The cumulative incidence of death and myocardial infarction was similar in both groups (11.0 vs. 9.7%, P=0.51). Repeat revascularization was performed in 21.1 and 25.8% of patients, respectively (P=0.12). The rate of very late stent thrombosis (1-5 years of follow-up) was very low in both groups (2.0 vs. 0.7%, P=0.12). CONCLUSION: The benefits of SES in STEMI patients in terms of reducing MACCE faded over time. We found no safety concerns in terms of SES in the long term, with extremely low rates of very late stent thrombosis.

Kinetic and structural features of a dyestuff coaggregation studied by time-resolved static light scattering.

A binary dyestuff aggregate with a distinct stoichiometry is formed in dilute aqueous solution upon addition of Mg(2+) ions. The aggregation process was investigated with time-resolved multiangle static light scattering resulting in a sequence of static scattering curves. The scattering curves were analyzed with respect to the aggregation kinetics as well as the structure of the growing aggregates. The aggregation kinetics was based on the time evolution of the weight-averaged molar mass values extracted from the intercepts of the static scattering curves. A kinetic model that considers solely a nucleation step and monomer addition in its most simple form was developed in order to describe the evolution of time-dependent mass data. In addition, a kinetic model introduced by Lomakin et al. (Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 1125) for the description of ß-amyloid aggregation was adapted to the same experimental data. Application of the two kinetic models offered significant information on the role of magnesium ions within the aggregation process and provided a deeper understanding of the aggregation mechanism. Correlation of the size parameters extracted from the initial slopes of the scattering curves with the respective mass data as well as direct fitting of the scattering curves with the wormlike chain model yield a consistent set of model parameters.

Co-aggregation of two anionic azo dyestuffs at a well-defined stoichiometry.

The present work investigates the formation of well-defined heteroaggregates from a binary mixture of a red and a yellow azo-dyestuff in the presence of Mg(2+) ions. Combined static and dynamic light scattering together with laser induced liquid bead ion desorption mass spectrometry (LILBID-MS) has been applied to characterize the states of the pure red dye and the pure yellow dye as well as of their mixture in aqueous solution without Mg(2+). These experiments indicated that a structural reorganization on a molecular scale takes place as soon as the two dyes are combined. Solutions of the combined red and yellow dye contain micelle-like mixed entities with a size of a few tenths of nanometers. Upon the addition of Mg(2+), these micelles vanish in favor of elongated heteroaggregates, which grow by a stepwise addition of smaller building units. As unraveled by UV/vis spectroscopy, the heteroaggregates that are formed from the red and yellow azo dye in the presence of Mg(2+) obey a stoichiometric ratio of the two components of 1:1. A new multiangle scattering instrument allowed us for the first time to follow this aggregation process at the stoichiometric ratio by time-resolved combined static and dynamic light scattering, thereby providing further aspects of the worm-like nature of the growing heteroaggregates.

Gender differences in long-term outcome after primary percutaneous intervention for ST-segment elevation myocardial infarction.

BACKGROUND: Previous studies on gender differences in outcome in patients with ST segment elevation myocardial infarction (STEMI) have been performed, but most of those are from before the current era of PCI technique and medical therapy and have a short duration of follow-up. The objective of our study is to assess the influence of gender on long-term outcome in patients with STEMI who underwent primary percutaneous intervention (PCI) between January 2006 and May 2008. METHODS: Two-year follow-up data from 202 female and 668 male patients undergoing primary PCI for STEMI were available from the DEBATER (A Comparison of Drug Eluting and Bare Metal Stents for Primary Percutaneous Coronary Intervention with or without Abciximab in ST-segment elevation Myocardial Infarction: The Eindhoven Reperfusion Study) trial database. The primary endpoint was major adverse cardiac events (MACE), defined as the composite of death, myocardial infarction, and target vessel revascularization. RESULTS: Women were older (64.7 ± 11.7 vs. 59.0 ± 10.7; P < 0.001), and had more often diabetes mellitus (15% vs. 9%; P = 0.01) and hypertension (44% vs. 25%; P < 0.001). At two years, the rate of MACE was significantly higher in women (21% vs. 14%; P = 0.02). The mortality rate in women was 8% versus 2.6% in men (P < 0.001). However, multivariate analysis after adjustment for age and the baseline characteristics hypertension, smoking, diabetes mellitus, stent diameter, and time between onset of symptoms and arrival of the ambulance showed similar MACE and mortality rates in men and women. CONCLUSION: Women have higher rates of both MACE and mortality after primary PCI for STEMI compared to men because of higher age with higher baseline risk profiles.

Variation of cardiac troponin I and T measured with sensitive assays in emergency department patients with noncardiac chest pain.

BACKGROUND: New-generation high-sensitivity assays for cardiac troponin have lower detection limits and less imprecision than earlier assays. Reference 99th-percentile cutoff values for these new assays are also lower, leading to higher frequencies of positive test results. When cardiac troponin concentrations are minimally increased, serial testing allows discrimination of myocardial infarction from other causes of increased cardiac troponin. We assessed various measures of short-term variation, including absolute concentration changes, reference change values (RCVs), and indices of individuality (II) for 2 cardiac troponin assays in emergency department (ED) patients. METHODS: We collected blood from patients presenting with cardiac chest pain upon arrival in the ED and 2, 6, and 12 h later. Cardiac troponin was measured with the high-sensitivity cardiac troponin T (hs-cTnT) assay (Roche Diagnostics) and a sensitive cTnI assay (Siemens Diagnostics). Cardiac troponin results from 67 patients without acute coronary syndrome or stable angina were used in calculating absolute changes in cardiac troponin, RCVs, and II. RESULTS: The 95th percentiles for absolute change in cardiac troponin were 8.3 ng/L for hs-cTnT and 28 ng/L for cTnI. Within-individual and total CVs were 11% and 14% for hs-cTnT and 18% and 21% for cTnI, respectively. RCVs were 38% (hs-cTnT) and 57% (cTnI). The corresponding log-normal RCVs were +46%/-32% for hs-cTnT and +76%/-43% for cTnI. II values were 0.31 (cTnI) and 0.12 (hs-cTnT). CONCLUSIONS: The short-term variations and IIs of cardiac troponin were low in ED patients free of ischemic myocardial necrosis. The detection of cardiac troponin variation exceeding reference thresholds can help to identify ED patients with acute myocardial necrosis whereas variation within these limits renders acute coronary syndrome unlikely.

Comparison of drug-eluting and bare-metal stents for primary percutaneous coronary intervention with or without abciximab in ST-segment elevation myocardial infarction: DEBATER: the Eindhoven reperfusion study.

OBJECTIVES: The goal of this study was to demonstrate superiority of sirolimus-eluting stents (SES) over bare-metal stents (BMS) and of abciximab over no abciximab in primary percutaneous coronary intervention (PCI). BACKGROUND: Drug-eluting stents (DES) are increasingly used in primary PCI, but the recommendations for use in primary PCI are based on a few randomized controlled trials with selected patients. The usefulness of abciximab in primary PCI is not established. METHODS: Nine hundred seven patients referred to the Catharina Hospital were randomized to SES or BMS, and to abciximab or no abciximab in a prospective, randomized, open 2 × 2 factorial trial with blinded evaluation. Primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), defined as the composite of death, myocardial infarction (MI), stroke, repeat revascularization, and bleeding at 1 year (stent arm) and the composite of death, target vessel MI, target vessel revascularization (TVR), and bleeding at 30 days (abciximab arm). RESULTS: At 1 year, the rate of MACCE was lower in the SES arm (16.5% vs. 25.8%, p = 0.001), mainly driven by less repeat revascularization (9.8% vs. 16.8%; p = 0.003) and without influencing the cumulative incidence of death and MI (5.2% vs. 5.8%; p = 0.68). At 30 days, the rate of the composite of death, target vessel MI, TVR, and bleeding was lower in the abciximab arm (8.2% vs. 12.4%, p = 0.04), mainly driven by less TVR due to less stent thrombosis (1.2% vs.7.4%, p < 0.001). However, bleeding complications occurred more frequently in the abciximab group (5.7% vs. 2.8%, p = 0.03). CONCLUSIONS: Primary PCI with SES reduces adverse events at 1 year, mainly by reduction of repeat revascularization, whereas abciximab reduces early stent thrombosis, at the expense of more bleeding complications. (Comparison of Drug Eluting and Bare Metal Stents With or Without Abciximab in ST Elevation Myocardial Infarction [DEBATER]; NCT00986050).

Molecular recognition with 2,4-diaminotriazine-functionalized colloids.

New polymeric colloids functionalized with 2,4-diaminotriazine residues have been prepared. The functionalities provide a triple hydrogen bond motif with a donor-acceptor-donor (DAD) pattern. The colloids are based on cross-linked poly-4-methoxymethyl styrene and are polymerized by means of surfactant-free emulsion polymerization. The reaction pathway including five steps was successfully tracked and verified via (13)C CP/MAS solid-state NMR. Characterization of the colloids was done by combined static and dynamic light scattering and indicates a compact spherical particle shape. In solvents with the appropriate polarity, intercolloidal hydrogen bonding was enabled, including colloidal aggregation. In highly dilute solutions of THF, this aggregation was recordable by means of time-resolved static light scattering experiments. If THF was saturated with uracil, then aggregation could be completely inhibited. Uracil bears a triple hydrogen bond motif of the form acceptor-donor-acceptor (ADA) and is a direct antagonist of 2,4-diaminotriazine. The charging of the colloids with uracil via hydrogen bond formation as a typical molecular recognition mechanism could be confirmed by IR spectroscopy.

Self-localization of polyacrylic acid molecules on polar ZnO(0001)-Zn surfaces.

The adsorption of single polyacrylic acid (PAAc) molecules was investigated on stepped hydroxide-stabilized polar ZnO(0001)-Zn surfaces using atomic force microscope (AFM) topography and force distance spectroscopy. Stepped surfaces of ZnO(0001)-Zn were prepared by a wet chemical etching procedure and PAAc molecules were adsorbed from aqueous NaClO(4) solutions. AFM single molecule topography studies could be utilized to show that polyacrylic acid molecules specifically adsorb on the non-polar (10-10) step edge faces at low ionic strengths. The radius of gyration of the dissolved PAAc in aqueous solution was measured by means of static light scattering experiments yielding a radius of gyration of R(g)=136 nm at pH 7.4 in 50 mM NaClO(4)/NaOH solution, which is in good agreement with the size of the adsorbed PAAc molecules as measured using AFM. The obtained results could be rationalized in terms of binding-site configurations at step edges and the effect of the chemical environment on both local electric double layer charge and molecular conformation of the PAAc molecules. The point of zero charge of the ZnO(10-10) surface was measured with chemical force microscopy to be pH(PZC)=10.2 ± 0.2. The specific adsorption of polyacrylic acid at non-polar ZnO step-edges can be explained by coordinative bonds formed between the carboxylic acid group and the Zn-surface atoms. On the hydroxide stabilized polar surface only weak hydrogen bonds can be formed in addition to van-der-Waals forces. Thus a "diffusion and trapping" mechanism keeps the adsorbed PAAc molecules mobile on the ZnO(0001)-Zn surface terraces due to small interaction forces until they are trapped at the (10-10) step faces by stronger coordinative bonds from the carboxylic groups to zinc atoms located in the first atomic layer of the crystal structure.

Rapid detection of myocardial infarction with a sensitive troponin test.

Rapid identification and treatment of patients with a myocardial infarction (MI) is mandatory. We studied the diagnostic capacities of a sensitive troponin assay for detection of MI in emergency department patients within 2 hours after arrival. The study included 157 patients suspected of having non-ST-elevation acute coronary syndrome. Blood was drawn on arrival (T0) and 2 (T2), 6, and 12 hours later. At T2, a troponin concentration above the MI cutoff is 87% sensitive and 100% specific for MI detection (positive predictive value [PPV], 100%; negative predictive value [NPV], 96%). If a difference of more than 30% between the troponin measurements at T0 and T2 in the absence of an absolute troponin increase above the 99th percentile of a reference population is also considered indicative of MI, the sensitivity increases to 100% and specificity decreases to 87% (PPV, 70%; NPV, 100%). Sensitivity and specificity of creatine kinase-MB and myoglobin are lower than those of troponin. By using a sensitive troponin assay and simple algorithms, the diagnosis of MI can be determined within 2 hours after arrival at the emergency department. Measurement of myoglobin and creatine kinase-MB has no added value.

Initial results and long-term clinical follow-up of an amorphous hydrogenated silicon-carbide-coated stent in daily practice.

The hemocompatibility and biocompatibility of a stent are determined by the physical and electrochemical properties of the stent surface. The aim of this study was to determine the feasibility, safety and efficacy of implantation of a stent coated with silicon carbide. Baseline characteristics were collected prospectively. The occurrence of cardiac adverse events and the angina score were assessed at clinical follow-up. A total of 193 Tensum stents were implanted in 174 patients. In hospital, one patient experienced stent thrombosis and in 6% of the patients a creatinine kinase elevation to 240 U/l or more occurred. Long-term follow-up was performed in 172 patients, with a mean follow-up of 454 +/- 181 days. Ninety-seven per cent were still alive, 15% had undergone target-vessel revascularization, and 2% had angiographic restenosis and were treated with medication only. Seventy-one per cent of the patients were free of anginal complaints, and 20% had anginal complaints in Canadian Cardiac Society class I or II. The Tensum coronary stent showed to be a safe and efficacious device in this study, with a high primary success rate and favorable long-term clinical followup.