Risk-Adjusted Capitation Payments: How Well Do Principal Inpatient Diagnosis-Based Models Work in the German Situation? Results From a Large Data Set

The Risk Adjustment Reform Act of 2001 mandates that a health-status-based risk adjustment mechanism has to be implemented in Germany's Statutory Health Insurance system by January 1, 2007. German parliament decided this as with the existing demographic risk adjustment model, that means there is cream skimming and sickness funds hesitate to engage in managing care for the chronical ill. Four approaches were used to test the feasibility of incorporating use of diagnosis as a proxy measure for health status in a German risk adjustment formula. The first two models used standard demographic and socio-demographic variables. The other two models are separately incorporating a simple binary indicator for hospitilization and Hierarchical Coexisting Conditions (HCCs: DxCG® Risk Adjustment Software Release 6.1) using inpatient diagnosis. Age and gender grouping accounted for 3.2% of the variation in total expenditures for concurrent as well as prospective models. The current German risk adjusters age, sex, and invalidity status account for 5.1% and 4.5% of the variance in the concurrent and prospective models respectively. There are substantial increases in explanatory power, however, when HCCs are added. Age, gender, invalidity status and HCC covariates explain about 37% of the variations of the total expenditures in a concurrent model and roughly 12% of the variations of total expenditures in a prospective model. For high-risk (cost) groups, substantial underprediction remains; conversely, for the low-risk group, represented by enrolees who did not show any health care expense in the base year, all of the models over-predict expenditure. --Risk Adjustment,HCCs,Germany

Contribution of ipsilesional versus contralesional pyramidal tract plasticity

Schlaganfall trägt zu erhöhter Mortalität und Morbidität trotz akut intensivmedizinischer Behandlung. Trotz vielversprechenden Ergebnisse von Seite der Akutbehandlung, die preklinische und klinische Versuche, die die Morbidität und Mortalität beim Schlaganfall in die postakute bis chronische Phase zu reduzieren versuchen, bleiben frustrierend. Nach dem Schlaganfall, das Hirnparenchym ist einem Reorganisationsprozess ausgesetzt indem vertiefte interzelluläre und zellulär-extrazelluläre Interaktionen eine wichtige Rolle spielen. Das Ontogenese Software wird „restarted“ und damit die endogene Plastizität nach dem Schlaganfall steigt. In wie fern wir diese Eigenschaft für therapeutische Zwecke „ausbeuten“ können bleibt bis jetzt unklar, allerdings man beobachtet bereits in viele Studien eine breitere Therapiefenster mit verlängertem Effekt und Erholungspotenzial nach dem Schlaganfall. In unserem Projekt haben wir mittels mehreren Readouts die Effekten von Erythropoietin (EPO) und Vascular endothelial growth factor (VEGF) auf die Neuroplastizität der langen Bahnen nach dem Schlaganfall untersucht. VEGF ist ein Wachstumsfaktor mit pleiotropen Effekte nach dem Schlaganfall und ist vor allem in die Astroglia und Mikroglia zusammen mit dem Rezeptoren VEGFR1 und VEGFR2 zu finden. In die akute Schlaganfall Phase VEGF ist für verschiedene Effekten in die Penumbra Region zuständig wie Förderung des neuronalen Überlebens, der Angiogenese Prozessen, der Proliferation von neuralen Stamzellen, deren Migration und Differenzierung. Anhalt neuen Studien wurde den VEGFR2 in den kontralesionalen Motorkortex nach dem Schlaganfall identifiziert . Diese Entdeckung weisst indirekt auf einer funktionelle Rolle der VEGF auf die kontralesionale Hemisphäre. Bis jetzt bleibt allerdings die Rolle der VEGF Therapie in die axonale Plastizität der langen Bahnen nach dem Schlaganfall unerforscht und dadurch auch seiner möglichen therapeutischen Rolle in die funktionelle Erholung. EPO ist ein Wachstumsfaktor mit einem breiten Spektrum der schon für klinische Verwendung zugelassen ist und damit zu einer schnelleren Translationsphase von preklinischen zu klinischen Experimenten geeignet ist. Die erste klinische Studie in der Erythropoietin nach dem Schlaganfall untersucht worden ist, zeigte eine Verbesserung der neurologischen Outcome mit Verkleinerung der ischämischen Schaden. In eine weitere Studie wurde dann der Effekt von EPO in 522 Patienten untersucht und zeigte dass die Verabreichung des EPO zusammen mit recombinant tissue-plasminogen activator (rt-PA) akut nach dem Schlaganfall zu einer signifikanten Nachblutung, Hirnödem und thromboembolische Ereignisse führte. Eine Falschinterpretation dieser Studie wird in die Zukunft für eine Ablehnung der EPO Therapie in Schlaganfall führen, obwohl eine alleinige Verabreichung des Epo eine Verbesserung zeigte. Unsere Studie untersucht die Effekte der Epo Therapie verabreicht drei Tage nach dem Schlaganfall mit Fokus auf die axonale Plastizität und funktionelle Erholung. Als Schlaganfall Model wurde eine 30 minutige Okklusion der A. cerebri media (MCAO) linkshemisphärisch durchgeführt. Die Verabreichung der Wachstumsfaktoren erfolgte am dritten postoperativen Tag mittels Alzet Pumpen die intraventrikulär implantiert wurden und eine kontinuierliche Verabreichung für verschiedene Zeitspannen gewährleistete. Als Kontrolle wurden die Pumpen mit NaCl 0.9% gefüllt und gemäss dem gleichen Protokoll intraventrikulär verabreicht. Sechs Wochen nach dem Schlaganfall und Therapie wurden die motorische Kortexanteile ipsi- und kontralesional mittels anterograden Tracttracers [Biotinyliertes Dextrane amid (BDA) in den kontralesionalen Motorkortex und Cascade Blue (CB) in den ipsilesionalen Motorkortex] markiert. Zwei Monate Postischämie wurden die Mäuse in Narkose getötet und das Gewebe für weitere molekularbiologische, biochemische, enzymologische, zytologische und genetische Untersuchungen verwendet. Die funktionelle Erholung als Korrelat zu Neurorehabilitation nach dem Schlaganfall wurde mittels RotaRod test, Grips strength test und Anxiety Test untersucht. Gemäss unseren Ergebnisse, VEGF und EPO Therapie verabreicht drei Tage nach dem Schlaganfall unterstützen die funktionelle Erholung durch koordinierte jedoch unterschiedliche Mechanismen die die Plastizität der langen Bahnen in der kontralesionalen Hemisphäre stimulieren. EPO zeigte vor allem eine vermehrte Translation der Plastizitätsgenen in der kontralesionalen Hemisphäre nach dem Schlaganfall die für eine erhöhte axonale Plastizität kontralesional verantwortlich waren. VEGF therapierten Tieren zeigten auch Erhöhung der axonalen Plastizität nach dem Schlaganfall kontralesional aber auf molekularer Ebene war das Effekt am besten durch eine Unterregulation von Plastizität hemmenden Substanzen in der Extrazellulären Matrix zu erklären.Stroke incidence is increasing due to the rapidly aging population in developed countries. Whereas untreated acute middle cerebral artery occlusion (MCAO) causes death in 20% of patients and long-term disability in more than 70% of patients, acute stroke therapy with rapid vessel recanalization significantly reduces mortality without influencing functional recovery beyond the acute stroke phase. This lack of functional recovery suggests a need for innovative therapies that can restore function after stroke. The purpose of these studies was to examine the effects of delayed administration of the growth factors erythropoietin (Epo) and vascular endogenous growth factor (VEGF) on functional neurological recovery and pyramidal tract plasticity in mice. The first study investigated how subacute delivery of Epo, starting at 3 days after stroke onset and continuing for 30 days (1 I.U. /day or 10 I.U. /day; via mini osmotic pump), influenced neuronal survival, axonal sprouting and neurological function recovery in C57Bl6/j mice submitted to 30-min MCAO. Epo administered in a 10 I.U. /day dose, in contrast to the 1 I.U. /day administration, showed a significant increase in neuronal survival and CD31 + newly-formed capillaries. This vascular growth enabled further neuroregeneration processes. Functional behavioral tests showed a significant improvement of motor coordination (RotaRod test) and grip strength (Grips strength test) among mice with 10 I.U. /day Epo administration, with no improvement for the low dose group. To investigate the neurological changes underlying these results, two anterograde tract tracers (dextrane amines) were injected in the motor cortex ipsilateral and contralateral to the ischemic lesion, in mice treated with the higher Epo dose. Histological evaluation of the tracers, both at the level of rubral and facial nucleus, showed that functional recovery in these animals was due to an increase of contralateral projections, accompanied by a compensatory decrease of ipsilateral projections. In the second study, VEGF was investigated due to its dual actions on vessels and neurons, which have potential for promoting long distance axonal plasticity in the ischemic brain. Mice were submitted to 30 minutes MCAO, followed by the intraventricular delivery of normal saline or VEGF (0.004 or 0.02 µg/day) starting 3 days post-ischemia. The outcome parameters were functional neurological recovery, long distance axonal plasticity by anterograde tract tracing and cellular and molecular responses examined by histochemistry, RT-PCR and Western blots. VEGF promoted neurological recovery when administered at the higher dosage, by stimulating long distance axonal plasticity in the contralesional but not ipsilesional pyramidal tract system. This observation was accompanied by deactivation of matrix metalloproteinase-9 (MMP9) in the ipsilesional brain tissue and downregulation of axonal growth inhibitors and guidance molecules in the contralesional brain tissue. The results support the concept that brain plasticity is consistent with coordinated axonal growth responses both ipsilateral and contralateral to the site of stroke. Considering that Epo is well tolerated in humans, clinical studies are now conceivable in which Epo is applied in patients in the post-acute stroke phase

Post-acute delivery of erythropoietin induces stroke recovery by promoting perilesional tissue remodelling and contralesional pyramidal tract plasticity

The promotion of post-ischaemic motor recovery remains a major challenge in clinical neurology. Recently, plasticity-promoting effects have been described for the growth factor erythropoietin in animal models of neurodegenerative diseases. To elucidate erythropoietin's effects in the post-acute ischaemic brain, we examined how this growth factor influences functional neurological recovery, perilesional tissue remodelling and axonal sprouting of the corticorubral and corticobulbar tracts, when administered intra-cerebroventricularly starting 3 days after 30 min of middle cerebral artery occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day), increased grip strength of the contralesional paretic forelimb and improved motor coordination without influencing spontaneous locomotor activity and exploration behaviour. Neurological recovery by erythropoietin was associated with structural remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival, increased angiogenesis and decreased reactive astrogliosis that resulted in reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal tract into the brainstem was observed in vehicle-treated ischaemic compared with non-ischaemic animals, as shown by injection of dextran amines into both motor cortices. Despite successful remodelling of the perilesional tissue, erythropoietin enhanced axonal sprouting of the contralesional, but not ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover, molecular biological and histochemical studies revealed broad anti-inflammatory effects of erythropoietin in both hemispheres together with expression changes of plasticity-related molecules that facilitated contralesional axonal growth. Our study establishes a plasticity-promoting effect of erythropoietin after stroke, indicating that erythropoietin acts via recruitment of contralesional rather than of ipsilesional pyramidal tract projection

Vascular endothelial growth factor induces contralesional corticobulbar plasticity and functional neurological recovery in the ischemic brain

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor, which also has neuroprotective activity. In view of these dual actions on vessels and neurons, we were interested whether VEGF promotes long distance axonal plasticity in the ischemic brain. Herein, we show that VEGF promotes neurological stroke recovery in mice when delivered in a delayed way starting 3 days after middle cerebral artery occlusion. Using anterograde tract-tracing experiments that we combined with histochemical and molecular biological studies, we demonstrate that although VEGF promoted angiogenesis predominantly in the ischemic hemisphere, pronounced axonal sprouting was induced by VEGF in the contralesional, but not the ipsilesional corticobulbar system. Corticobulbar plasticity was accompanied by the deactivation of the matrix metalloproteinase MMP9 in the lesioned hemisphere and the transient downregulation of the axonal growth inhibitors NG2 proteoglycan and brevican and the guidance molecules ephrin B1/2 in the contralesional hemisphere. The regulation of matrix proteinases, growth inhibitors, and guidance molecules offers insights how brain plasticity is controlled in the ischemic brain

Towards Patient-Oriented Diabetes Care: Results from Two KORA Surveys in Southern Germany

Objective. This study aims to examine the relationship of diabetes care processes and patient outcomes with an expanded set of indicators regarding patient-oriented care delivery, such as treatment satisfaction, the quality of patient-physician relationship, and a wider range of patient outcomes such as self-management, health behaviour, disease-related burden, and health-related quality of life (HRQL). Methods. The study population consisted of 486 participants with type 2 diabetes in two population-based follow-up surveys, conducted in 2003 to 2005 and 2006 to 2008 in Southern Germany. Data were self-reported and questionnairebased, including the SF-12 for HRQL. Multiple regression models were used to identify associations between care processes and outcomes with adjustment for confounders. Results. Frequent medical examinations increased the likelihood of self-monitoring activities, such as foot care. A positive patient experienced relationship with their physician is associated with higher adherence to medical recommendations, such as medication intake, and the score of the SF-12 mental component. Participants with diabetesrelated complications reported higher levels of medical examinations and multiprofessional care. Conclusions. Indicators of patientoriented care should become an indispensable part of diabetes clinical practice guidelines with the aim of striving for more effective support of patients

Ultrasound Perfusion Imaging for the Detection of Cerebral Hypoperfusion After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND Delayed cerebral ischemia increases mortality and morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Various techniques are applied to detect cerebral vasospasm and hypoperfusion. Contrast-enhanced ultrasound perfusion imaging (UPI) is able to detect cerebral hypoperfusion in acute ischemic stroke. This prospective study aimed to evaluate the use of UPI to enable detection of cerebral hypoperfusion after aSAH. METHODS We prospectively enrolled patients with aSAH and performed UPI examinations every second day after aneurysm closure. Perfusion of the basal ganglia was outlined to normalize the perfusion records of the anterior and posterior middle cerebral artery territory. We applied various models to characterize longitudinal perfusion alterations in patients with delayed ischemic neurologic deficit (DIND) across the cohort and predict DIND by using a multilayer classification model. RESULTS Between August 2013 and December 2015, we included 30 patients into this prospective study. The left-right difference of time to peak (TTP) values showed a significant increase at day 10-12. Patients with DIND demonstrated a significant, 4.86 times increase of the left-right TTP ratio compared with a mean fold change in patients without DIND of 0.9 times (p = 0.032). CONCLUSIONS UPI is feasible to enable detection of cerebral tissue hypoperfusion after aSAH, and the left-right difference of TTP values is the most indicative result of this finding

Exposure to ultrafine carbon particles at levels below detectable pulmonary inflammation affects cardiovascular performance in spontaneously hypertensive rats

<p>Abstract</p> <p>Background</p> <p>Exposure to particulate matter is a risk factor for cardiopulmonary disease but the underlying molecular mechanisms remain poorly understood. In the present study we sought to investigate the cardiopulmonary responses on spontaneously hypertensive rats (SHRs) following inhalation of UfCPs (24 h, 172 μg·m^-3), to assess whether compromised animals (SHR) exhibit a different response pattern compared to the previously studied healthy rats (WKY).</p> <p>Methods</p> <p>Cardiophysiological response in SHRs was analyzed using radiotelemetry. Blood pressure (BP) and its biomarkers plasma renin-angiotensin system were also assessed. Lung and cardiac mRNA expressions for markers of oxidative stress (hemeoxygenase-1), blood coagulation (tissue factor, plasminogen activator inhibitor-1), and endothelial function (endothelin-1, and endothelin receptors A and B) were analyzed following UfCPs exposure in SHRs. UfCPs-mediated inflammatory responses were assessed from broncho-alveolar-lavage fluid (BALF).</p> <p>Results</p> <p>Increased BP and heart rate (HR) by about 5% with a lag of 1–3 days were detected in UfCPs exposed SHRs. Inflammatory markers of BALF, lung (pulmonary) and blood (systemic) were not affected. However, mRNA expression of hemeoxygenase-1, endothelin-1, endothelin receptors A and B, tissue factor, and plasminogen activator inhibitor showed a significant induction (~2.5-fold; p < 0.05) with endothelin 1 being the maximally induced factor (6-fold; p < 0.05) on the third recovery day in the lungs of UfCPs exposed SHRs; while all of these factors – except hemeoxygenase-1 – were not affected in cardiac tissues. Strikingly, the UfCPs-mediated altered BP is paralleled by the induction of renin-angiotensin system in plasma.</p> <p>Conclusion</p> <p>Our finding shows that UfCPs exposure at levels which does not induce detectable pulmonary neutrophilic inflammation, triggers distinct effects in the lung and also at the systemic level in compromised SHRs. These effects are characterized by increased activity of plasma renin-angiotensin system and circulating white blood cells together with moderate increases in the BP, HR and decreases in heart rate variability. This systemic effect is associated with pulmonary, but not cardiac, mRNA induction of biomarkers reflective of oxidative stress; activation of vasoconstriction, stimulation of blood coagulation factors, and inhibition of fibrinolysis. Thus, UfCPs may cause cardiovascular and pulmonary impairment, in the absence of detectable pulmonary inflammation, in individuals suffering from preexisting cardiovascular diseases.</p