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Liang R.,University of Heidelberg | Liang R.,Dalian Medical University | Nickkholgh A.,University of Heidelberg | Kern M.,University of Heidelberg | And 5 more authors.
Molecular Nutrition and Food Research | Year: 2011

Scope: Polyphenolic constituents of green tea (Camellia sinensis) have been shown to be potent scavengers of reactive oxygen species (ROS). Thus, this study was designed to assess its effects after liver ischemia-reperfusion. Methods and results: Fasted Sprague-Dawley rats were gavaged with different concentrations of green tea extract (GTE) 2h before 90min of warm ischemia of the left lateral liver lobe (30% of liver). Controls were given the same volume of Ringer's solution. A preparation of pentobarbital sodium (intraperitoneal) and ketamine (intramuscular) was used for anesthesia. After reperfusion, transaminases, liver histology, hepatic microcirculation, and both phagocytosis of latex bead particles as well as the expression of tumor necrosis alpha (TNF-α) to index cellular activation were investigated. Furthermore, the expression of superoxide dismutase (Mn-SOD) was assessed. After 90min of warm ischemia aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) increased dramatically to 1946±272/3244±757U/L, 1680±134/2080±379U/L, and 7857±1851/2036±1193U/L at 2/6h, respectively. GTE (200mg/kgbody weight) significantly prevented this increase in a dose-dependent manner by 21-51% at 2h and 29-34% at 6h, respectively. Histology confirmed the protective effects while both TNF-α expression and phagocytosis of latex beads by Kupffer cells (KCs) were significantly reduced. GTE intake significantly increased the expression of manganese superoxide dismutase. In vivo microscopy revealed improved acinar and sinusoidal perfusion after GTE. Conclusion: Preconditioning with a single oral dose of GTE ameliorates ischemia-reperfusion injury in liver. Decreased cellular activation and improved microcirculation are the proposed mechanisms. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Donath C.,Psychiatric University Clinic Erlangen | Grassel E.,Psychiatric University Clinic Erlangen | Grossfeld-Schmitz M.,Psychiatric University Clinic Erlangen | Menn P.,Helmholtz Center Munich | And 6 more authors.
BMC Health Services Research | Year: 2010

Background: More than 90% of dementia patients are cared for by their general practitioners, who are decisively involved in the diagnosis, therapy and recommendation of support services. Objective: To test whether special training of general practitioners alters the care of dementia patients through their systematic recommendation of caregiver counseling and support groups. Method. 129 general practitioners enrolled 390 dementia patients and their informal caregivers in a prospective, three-arm cluster-randomized 2-year study. Arm A constituted usual care, in Arm B and C support groups and caregiver counseling (in Arm B one year after baseline, in Arm C at baseline) were recommended by the general practitioners. The general practitioners received arm-specific training. Diagnostic and therapeutic behavior of physicians was recorded at baseline. Informal caregivers were questioned in follow-up after 2 years about the utilization of support services. Results. The diagnostic behavior of the general practitioners conforms to relevant guidelines. The procedure in newly-diagnosed patients does not differ from previously diagnosed patients with the exception of the rate of referral to a specialist. About one-third of the newly-diagnosed dementia patients are given an anti-dementia drug. The utilization of support groups and counseling increased five- and fourfold, respectively. Utilization of other support services remained low (< 10%), with the exception of home nursing and institutional short-term nursing. Conclusion. Trained general practitioners usually act in conformity with guidelines with respect to diagnosing dementia, and partly in conformity with the guidelines with respect to recommended drug therapy. Recommendations of support services for informal caregivers by the general practitioner are successful. They result in a marked increase in the utilization rate for the recommended services compared to offers which are not recommended by the general practitioner. © 2010 Donath et al; licensee BioMed Central Ltd.

Schneider H.,HealthEcon AG | Maheu E.,AP HP Saint Antoine Hospital | Cucherat M.,Service de Pharmacologie Clinique
Open Rheumatology Journal | Year: 2012

Objective: To perform a meta-analysis of randomized double-blind placebo-controlled clinical trials to assess the efficacy of a specific chondroitin sulfate preparation (Structum ®, Laboratoires Pierre Fabre, Castres; France) as a symptom-modifying drug in osteoarthritis (OA) of the knee. Methods: A Medline search was conducted up to October 2010 and two articles reporting two trials were identified; one additional trial was identified through contacting the producer of Structum ®. There was no evidence of heterogeneity across the trials and results were pooled using a fixed effects model. Results: Pooled results demonstrated a modest, but significant effect of Structum ® (1 g daily) over placebo on the reduction of pain during activity following a treatment period of 3-6 months of 6 mm (95% confidence interval (CI) -9.50, -1.72, p=0.005) on the visual analog scale (VAS) and a reduction in the algo-functional Index (AFI) by a weighted mean difference of -0.73 (95% CI -1.28 to -0.18, p=0.01). In addition, the pooled analysis demonstrated a statistically significant increase in OMERACT-OARSI responders in the Structum ®-treated patients by 20% (RR of 1.20 (95% CI 1.06 to 1.36, p=0.003)), compared to placebo. Conclusion: These results demonstrate that this chondroitin sulfate preparation (Structum ®) is effective on symptoms in patients with OA of the knee compared to placebo, and may therefore have a role in the management of patients with knee osteoarthritis of Kellgren-Lawrence grades II and III. © Schneider et al.

Neilson A.R.,HealthEcon AG | Sieper J.,Charité - Medical University of Berlin | Deeg M.,Pfizer
Rheumatology | Year: 2010

Objectives: To estimate the cost-effectiveness of etanercept (ETN) plus usual care (including NSAIDs) compared with usual care alone (including NSAIDs) in patients with severe AS in Germany. Methods: A mathematical model previously applied to the UK was adapted using resource use and cost data (for 2007) from the national database of the German Collaborative Arthritis Centres. Social health insurance (SHI) and societal perspectives were analysed. Assumptions on initial response and changes in health-related quality of life were based on Phase III randomized controlled trials. Initial treatment response according to British Society for Rheumatology guidelines were assumed as a conservative estimate in the German context. Long-term disease progression was based on the available literature. Incremental cost-effectiveness ratios (ICERs) were expressed as euros/quality-adjusted life year (QALY), for a cohort of 1000 patients over 25 years. Sensitivity analyses explored uncertainty in results. Results: In the base case, ETN plus usual care (including NSAIDs) yielded 1475 more QALYs at an additional cost of €80 827 668 (SHI) or €32 657 590 (societal) leading to an ICER of €54 815/QALY and €22 147/QALY, respectively. Over a shorter time horizon of 10 years, the ICERs were €59 006 and €29 815 for SHI and societal viewpoints, respectively. Assumptions having the largest impact on results included withdrawal rates from ETN, quality of life, disease costs and initial response. Conclusions: Cost-effectiveness for ETN in patients with severe AS in Germany differs according to the cost perspective. Study estimates were higher than in the UK but comparable with reported cost-effectiveness of anti-TNF treatments in patients with RA in Germany. © The Author 2010. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Starke J.,Hepathology and Nutrition | Schneider H.,HealthEcon AG | Alteheld B.,University of Bonn | Stehle P.,University of Bonn | Meier R.,Hepathology and Nutrition
Clinical Nutrition | Year: 2011

Background & aims: Strategies to treat malnutrition lack practicability in the hospital setting.The present study aimed at developing and evaluating a routinely manageable concept for an improved nutritional care of malnourished in-hospital patients. Methods: A randomized controlled intervention study was conducted. 132 risk patients defined by Nutritional Risk Screening 2002, were randomized to individualised nutrition support (intervention group [. n = 66]) or standard hospital care (control group [ n = 66]). Body weight, plasma vitamin levels, quality of life, complications, antibiotic therapies, readmissions and mortality were assessed. Results: Nutrition interventions led to higher intakes (mean [standard deviation]) in energy (1553 [341] kcal vs. 1115 [381] kcal, p < 0.001) and protein (65.4 [16.4] g vs. 43.9 [17.2] g, p < 0.001). Intervention patients (n = 66) kept their body weight in comparison to control patients (n = 66; 0.0 [2.9] kg vs. -1.4 [3.2] kg, p = 0.008). Positive effects on plasma ascorbic acid level (46.7 [26.7] μmol/l vs. 34.1 [24.2] μmol/l, p = 0.010), SF-36 function summary scale (37 [11] % vs. 32 [9] %, p = 0.030), number of complications (4/66 vs. 13/66, p = 0.035), antibiotic therapies (1/66 vs. 8/66, p = 0.033) and readmissions (17/64 vs. 28/61, p = 0.027) were recorded. Conclusions: Malnourished patients profit from nutrition support regarding nutrition status and quality of life. They have fewer complications, need fewer antibiotics and are less often re-hospitalised. © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Relja B.,Goethe University Frankfurt | Tttel E.,Goethe University Frankfurt | Breig L.,Goethe University Frankfurt | Henrich D.,Goethe University Frankfurt | And 3 more authors.
British Journal of Nutrition | Year: 2011

Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0•1 % polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2) mmHg for 60 min and resuscitated. Control groups (sham-ctrl and sham-GTE) underwent surgical procedures without H/R. At 2 h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P < 0•05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P < 0•05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanism. © 2011 The Authors.

Navarini A.A.,University of Zürich | Laffitte E.,Hopitaux Universitaires Of Geneva | Conrad C.,University of Zürich | Piffaretti P.,Wyeth Pharmaceuticals AG | And 3 more authors.
Swiss Medical Weekly | Year: 2010

Background: Evaluation of the current clinical treatment of psoriasis in Switzerland remains to be measured with the parameters cost-of-illness and quality of life. Objective: To obtain data on out-of-pocket expenses, costs of outpatient/office-based care and inpatient care for psoriasis, and to extrapolate total costs by state of severity to the entire Swiss population. Methods: 1200 retrospective surveys were distributed to patient members of the Swiss Psoriasis and Vitiligo Society, and 400 surveys to office-/hospital-based Swiss dermatologists. The reference year for data collection was 2005. Patients were stratified into three subgroups according to severity of disease. Costs of inpatient care were measured by the amount of hospital days of psoriatic patients from the Swiss Federal Hospital Statistics. Results: 383 patient questionnaires, and 170 cases documented by 57 dermatologists were analyzed. Out-of-pocket expenses/costs for ambulatory care per patient and year ranged from CHF 600-1100 for mild psoriasis to CHF 2400-9900 for severe psoriasis. Including costs for inpatient care of approximately CHF 60 million, the total annual costs for psoriasis in Switzerland in 2004/5 amounted to approximately CHF 314-458 million. Conclusions: Moderate-to-severe psoriasis is associated with a significant impact on the quality of life and at least 4-fold higher costs than mild psoriasis, indicating the need for efficient control of the disease. This cost-of-illness study provides specific health economic data for future healthcare decision making, particularly with the advent of new therapeutic agents for effective psoriasis control.

Brock E.,HealthEcon AG | Braunhofer P.,Vifor International AG | Troxler J.,Vifor Pharma AG | Schneider H.,HealthEcon AG
European Journal of Health Economics | Year: 2013

Objectives: Iron deficiency is common in pregnancy, postpartum, inflammatory bowel disease, chronic kidney disease, chronic heart failure, heavy uterine bleeding, cancer and following surgery. We estimate the budget impact (BI) on the Swiss mandatory health insurance associated with substituting iron sucrose (standard) with ferric carboxymaltose (new treatment) using real-life data.Methods: Resource use was based on recent primary data (Polyquest Prescriber Analysis, Anemia Patient Record Study in Switzerland). Personnel costs were estimated using the Swiss Tarmed fee-for-service reimbursement system. Drug costs and costs of materials used were based on official tariffs (Spezialitätenliste, MiGeL). Actual IMS sales data of both products were used to verify the BI model (1 CHF ≈ 1 USD, Jan 2013).Results: Ferric carboxymaltose was associated with cost savings of 30–44 % per patient per treatment cycle compared to iron sucrose. Costs per 200/500/1,000 mg total dosage treatment cycle were CHF 101/210/420 for ferric carboxymaltose and CHF 144/375/721 for iron sucrose. This results in cost savings of CHF 22–31 million across all indications in 2009. Savings were driven by personnel cost reductions (application time and number of applications). Sensitivity analyses confirmed these cost savings, even for the higher application costs of ferric carboxymaltose, with minimum savings of CHF 17 million per year.Conclusions: Treating iron deficiency involves substantial costs to the Swiss MHI which may be reduced by substituting iron sucrose with ferric carboxymaltose. The use of real-life data raises methodological questions about the fundamental compatibility of this data with the conceptual framework of BI analysis. © 2013, Springer-Verlag Berlin Heidelberg.

Schneider H.,HealthEcon AG | Dietrich E.S.,HealthEcon AG | Venetz W.P.,DataGen AG
International Journal of Environmental Research and Public Health | Year: 2010

In Switzerland a rapid increase in the total overweight population (BMI ? 25) from 30.3% to 37.3% and in the obese segment (BMI ? 30) from 5.4% to 8.1% was observed between 1992 and 2007. The objective of this study is to produce a projection until 2022 for the development of adult overweight and obesity in Switzerland based on four National Health Surveys conducted between 1992 and 2007. Based on the projection, these prevalence rates may be expected to stabilize until 2022 at the 2007 level. These results were compared with future projections estimated for France, UK, US and Australia using the same model. © 2010 by the authors; licensee Molecular Diversity Preservation International.

Pscherer S.,Klinikum Traunstein | Dietrich E.S.,HealthEcon AG | Dippel F.-W.,Sanofi S.A. | Neilson A.R.,HealthEcon AG
International Journal of Clinical Pharmacology and Therapeutics | Year: 2010

Objective: A one-year cost analysis comparing basal insulin analogues glargine (IG, Lantus®) versus detemir (ID, Levemir ®) in combination with oral antidiabetic drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes patients in Germany based on the results of a randomized controlled clinical trial (RCT). The trial demonstrated equivalent treatment efficacy.Materials and methods: Total direct diabetes treatment costs were estimated from the perspective of the German statutory health insurance (SHI) for the time horizon of one-year. Simulated resources included medication (insulin, oral antidiabetic drugs) and consumable items (needles, blood glucose test strips and lancets). Initial and final insulin doses per kg body weight and proportion of patients with once/twice daily insulin injection were taken from the above mentioned RCT. Unit costs were taken fromofficialGerman price lists and sources. Deterministic-(DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs were performed to test robustness of the results. Results: Average annual treatment costs per patient (base case) were € 849 for glargine and € 1,334 for detemir resulting in cost savings of € 486 per patient per year (36%). Costs of insulins were € 469 (IG) and € 746 (ID). Costs of consumable items amounted at € 380 (IG) and € 588 (ID) respectively. Sensitivity analyses confirmed the findings in favor of insulin glargine. PSA results found cost savings ranging from € 429 to € 608 (5th/95th percentiles). Conclusions: The current model estimated that insulin glargine was associated with lower annual treatment costs of € 486 (36%) compared to the use of insulin detemirwhile the same glycemic control is expected to be achieved. ©2010 Dustri-Verlag Dr. K. Feistle.

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