The treatment of chronic hepatitis C has considerably changed with the introduction of recent direct acting antivirals. These antivirals have sustained virologic response (SVR) rates above 90 % as ...well as reduced toxicity and treatment duration. Therefore, current German guidelines recommend these interferon-free regimens as first-choice treatment. Nevertheless, recent developments were accompanied by a significant increase in treatment costs, which led to extensive discussions on reasonable pharmaceutical prices. The aim of the current study was to analyze the average treatment costs and costs per patient cured for guideline treatment recommendations. Analyses were stratified according to genotype, treatment status (naive/experienced), and presence/absence of cirrhosis. Costs were separated in (1.) basic diagnostic procedures, (2.) monitoring, and (3.) pharmaceuticals. The calculation is based on a remuneration scheme in the statutory health insurance system. In treatment-naïve non-cirrhotic patients, the average cost is 41 766 €/SVR for the treatment with SOF/LDV calculated (PTV/r/OMV+DSV: 53 129 €/SVR). In treatment-naive cirrhotic patients, costs were 60 323 €/SVR (SOF/LDV+RBV) and 80 604 €/SVR (PTV/r/OMV+DSV+RBV). Treatment-experienced genotype 1 patients had average costs of 60 366 €/SVR for SOF/LDV treatment as well as 53 134 €/SVR for PTV/r/OMV+DSV±RBV treatment (cirrhotic patients: 62 208 €/SVR for SOF/LDV+RBV; 80 824 €/SVR for PTV/r/OMV+DSV+RBV). The average treatment costs per SVR in treatment-naive genotype 1 patients are comparable to previous standard of care treatments and lower in treatment-experienced patients. In other genotypes, treatment costs and costs per cure are significantly higher compared to previous standard of care. However, long-term modelling studies show that new regimens are cost-effective.
Summary
Viral hepatitis is a major public health problem affecting millions of people worldwide. Long‐term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The aim of ...the study was to assess outcomes and costs of treating patients with chronic hepatitis C in clinical practice in Germany. We carried out a prospective noninterventional study. Information on treatment outcomes, resource utilization and quality of life was provided by 281 physicians throughout Germany. Data of 3708 monoinfected HCV‐patients treated between 2008 and 2011 were analysed. Therapy consisted of peginterferon/ribavirin. Mean age of patients was 43.7 years, 60.3% were male and estimated duration of infection was 13.6 years. Predominantly genotype 1 (61.3%) or 3 (28.5%) infections were observed. Sustained viral response (SVR)‐rates in most frequently observed genotypes were 49.2% in GT‐1 and 61.9% in GT‐3 treatment‐naive patients (Relapser: GT‐1: 35.3% and GT‐3: 57.3%; Nonresponder: GT‐1: 25.0% and GT‐3: 33.3%). Average treatment costs were lowest in treatment‐naive patients (€18 965) and higher in patients who failed previous treatments (relapsers: €24 753; nonresponders: €19 511). Differences according to genotype were observed. Average costs per SVR in treatment‐naive patients were €44 744 for GT‐1 and €22 218 for GT‐3. Treatment was associated with a decrease in quality of life; post‐treatment quality of life was higher in patients achieving SVR. Our insight on real‐life treatment outcomes and costs can serve as a reference for a comparison with other treatments. There is high need for short‐term and long‐term cost‐effectiveness analysis in real‐life settings as newly introduced treatment strategies with direct acting antivirals result in high SVR‐rates but are more costly.
In medically ill patients, no contemporary double-blind head-to-head evaluation of low molecular weight heparin vs. unfractionated heparin (UFH) for the prevention of venous thromboembolic events is ...available.
To compare the efficacy and safety of certoparin with those of UFH.
In this double-blind, randomized, controlled trial, acutely ill, non-surgical patients aged > or = 70 years were randomized to certoparin (3000 U of anti-factor Xa once daily) or to UFH (5000 IU t.i.d.). The primary endpoint was the composite of proximal deep vein thrombosis as assessed by bilateral compression ultrasonography, symptomatic non-fatal pulmonary embolism and venous thromboembolism-related death, and was assessed by a blinded central adjudication committee. Non-inferiority margins were set at 1.8 for the odds ratio (OR) and 3.45% for the absolute difference.
Three thousand two hundred and thirty-nine patients aged 78.8 + or - 6.3 years were treated for 9.1 + or - 3.4 days. The incidence of the primary endpoint was 3.94% in the certoparin group and 4.52% in the UFH group, with a difference in proportions of - 0.59% 95% confidence interval (CI) -2.09 to 0.92; P < 0.0001 for non-inferiority, and an OR of 0.87 (95% CI 0.60-1.26; P = 0.0001 for non-inferiority). Major bleeding occurred in 0.43% of certoparin-treated patients and 0.62% of UFH-treated patients (OR 0.69; 95% CI 0.26-1.83). Any bleeding occurred at 3.20% in certoparin-treated patients vs. 4.58% in UFH-treated patients (OR 0.69; 95% CI 0.48-0.99; P < 0.05), and 5.73% of certoparin-treated patients and 6.63% of UFH-treated patients experienced serious adverse events. All-cause mortality was 1.27% in certoparin-treated patients and 1.36% in UFH-treated patients.
In acutely ill, non-surgical elderly patients, thromboprophylaxis with certoparin (3000 U of anti-FXa once daily) was non-inferior to 5000 IU of UFH t.i.d., with a favorable safety profile.
In Germany up to 800,000 persons are chronically infected with the hepatis C virus. This chronic disease is correlated with a significant morbidity and mortality. This is a consequence of the ...development of liver cirrhosis and hepatocellular carcinoma in a substantial proportion of the patients. Health quality of life is also affected by the infection. There are reliable standards available for diagnosis and treatment. Antiviral treatment is highly effective and the combination of pegylated interferon alpha with ribavirin leads to a sustained viral eradication in about 60% of the cases. The treatment is also cost-effective and results in an increased life expectancy. Costs for HCV treatment are favourable in comparison to other well accepted therapies and interventions and a reduction of future costs can be expected.Thus, active screening for HCV infected persons should be intensified to improve the quality of medical care. Early and broad treatment is potentially able to reduce the future burden of HCV-related diseases.
Subarachnoidal release of inflammatory cytokines (interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α) was characterised in 35 patients with subarachnoid haemorrhage (SAH) and control ...subjects and compared with development of complicating haemodynamic abnormalities in basal cerebral arteries and clinical outcome. Serial analysis allowed the observation of a subacute response profile of these key mediators of inflammation in the subarachnoidal space. This compartmentalised inflammatory host response was closely associated in time and extent with development of increased blood flow velocities in the basal cerebral vessels as recorded by transcranial Doppler sonography. Moreover, intrathecal secretion of inflammatory cytokines was significantly increased in patients with poor clinical outcome. Together, these findings suggest a role of excessive compartmentalised inflammatory host response in pathogenesis of cerebrovascular complications after SAH.
The costs of a guideline-based treatment in chronic hepatitis C infected people are unknown. The goal of HCV therapy is to achieve a sustained viral response and thereby to reduce morbidity and ...mortality due to complications of liver cirrhosis and hepatocellular carcinoma. This study analyses the costs of a guideline-based treatment based on the German guideline on the management of HCV infection. In addition, costs of newly introduced protease inhibitors were calculated. Costs for baseline diagnostics, monitoring and medical treatment were calculated according to the stage of the disease, the HCV genotype and viral response. Costs for baseline diagnostics account for € 302.75 and monitoring accounts for € 596 to € 1173. Dual therapy with pegylated interferon and ribavirin results in average costs of € 7709 to € 34 692. Total costs of a guideline-based treatment range between € 8,608 and € 36 167 depending on HCV genotype and length of therapy. With the introduction of protease inhibitors for HCV genotype 1 patients, costs of pharmaceuticals have increased further. Triple-therapy with telaprevir accounts for € 43 280 respectively € 54 844. Costs for Boceprevir treatment range from € 34 143 to € 60 990. Due to increasing costs, health-economic evaluations gain significant relevance and should be considered when implementing new treatment strategies.
SUMMARY
Butyrate, a short‐chain fatty acid released by colonic bacteria and administered therapeutically in inflammatory bowel diseases, exerts immunomodulatory properties. The aim of the study was ...to determine the functional consequences of butyrate exposure on the proinflammatory responsiveness of human intestinal epithelial cells (IEC). IL‐8 promoter activity in IEC pretreated with butyrate then exposed to proinflammatory stimuli was assayed by transfection of luciferase constructs. IL‐8 secretion was determined by ELISA and neutrophil migration by flow cytometry. Receptor mRNA was assessed by reverse transcriptase–polymerase chain reaction (RT‐PCR). Butyrate modulated proinflammatory IL‐8 secretion differentially in Caco‐2 and HT‐29 cells on the transcriptional level. Pointing to the potentially underlying mechanism of increased IL‐1β‐stimulated IL‐8 secretion in HT‐29 cells, butyrate up‐regulated IL‐1RI mRNA but not IL‐1RII. Butyrate pretreatment of IEC lines stimulated by IL‐1β modulated neutrophil migration significantly: reduction towards Caco‐2 and enhancement towards HT‐29/p cells. Pharmacological inhibition of protein tyrosine phosphatases or treatment with mesalamine or sulphasalazine diminished IL‐1β‐stimulated IL‐8 secretion by butyrate‐exposed HT‐29 cells substantially. Immunomodulatory effects of butyrate on IEC are functionally relevant for neutrophil migration. Pharmacological inhibition of enhanced IL‐1β‐mediated IL‐8 secretion in a subpopulation of IEC may improve the clinical efficacy of butyrate.
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