Costs and outcomes of treating chronic hepatitis C patients in routine care - results from a nationwide multicenter trial.

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.

[Costs of a guideline-based treatment of patients with chronic hepatitis C in the era of interferon-free treatment]. / Kosten einer leitliniengerechten Versorgung von Hepatitis-C-Patienten im Zeitalter Interferon-freier Therapien.

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.

[Health and Prevention Behaviour of Persons with and without Migration Background]. / Gesundheits- und Präventionsverhalten von Personen mit und ohne Migrationshintergrund.

Based on a sample of the Hannover registration office this project analyses the health and prevention behaviour of Russian- and Turkish-language migrants compared to natives. The project analysis revealed considerable differences, particularly concerning addiction behaviour and physical activities.

[School Development by Using Health Management: Indicator Toolbox as Quality Assurance Instrument for Self-Evaluation in Schools]. / Schulentwicklung durch Gesundheitsmanagement: Kennzahlentoolbox als Qualitätssicherungsinstrument für Selbstevaluation an Schulen.

Organisational development is crucial to health promotion in schools. The intervention "Learning to Live Healthy" is a new school health promotion strategy designed to develop schools into healthy environments for all those who work and study there. The aim of the study "School Development by using Health Management" is to introduce the management instrument balanced scorecard and to develop an indicator toolbox. This allows schools to evaluate the achievement of objectives, the implementation level of the measures and the changes in their organisation regarding health management.

[Implementing daily physical education in primary school - potentials and barriers from the involved actor's point of view]. / Täglichen Schulsport in der Grundschule implementieren - Potenziale und Barrieren aus Sicht der beteiligten Akteure.

OBJECTIVE: The objective was to determine to what extent daily physical education can be implemented in primary schools, what barriers exist and how to overcome the mentioned barriers. Moreover, it was analysed to what extent daily physical education is accepted by teachers, external trainers, parents and students. METHODS: Semi-structured interviews with parents (n=7), teachers (n=5) and external trainers (n=6) of the intervention schools. The intervention students (n=44) were surveyed within focus groups. RESULTS: All surveyed groups appraised the implementation of daily school sports as successful. The cooperation between the schools and the sports club should be maintained during a comprehensive implementation of daily physical education. Besides an improved lessons quality teachers and external trainers reported an improved social behaviour of the children. Parents perceived positive effects on the child development. All groups believe that daily physical education increases the enjoyment of children in sports. As a certain barrier a lack of resources (e. g., facilities, equipment, financial resources) in the schools were mentioned. CONCLUSIONS: The cooperation between the schools and the sports club proved to be an applicable model to implement daily physical education. The combination of teachers and external trainers can contribute to a higher lesson quality. Considering the perceived potentials of daily physical education by all surveyed groups, a comprehensive implementation of systematic daily physical activity promotion in the primary school setting should be tapped more strongly in future.

[Effectiveness and Cost-Effectiveness of Daily School Sport in the Primary School--Project: "fit for pisa"]. / Effektivität und Kosteneffektivität täglichen Schulsports in der Grundschule--das Projekt "fit für pisa".

The "fit for pisa" intervention implemented daily physical education at five primary schools in Göttingen. The results of the evaluation show an increase in physical activity among the students participating in the programme. At the same time sedentary behaviour, like watching television, decreased remarkably. In the long run the promotion of an active lifestyle had improved the body mass index. The study emphasises the need for government funding to implement the programme across the country.

[The Preventive Home Visit as a Preventive Intervention to Reach the Elderly--Effectiveness and Cost-Effectiveness of Different Ways of Approach]. / Der präventive Hausbesuch als zugehende Präventionsmaßnahme im Alter--Effektivität und Kosteneffektivität von Zugangswegen.

The aim of the study was a systematical further development of targeted approaches. Research questions were how elderly women and men could be motivated to participate in a preventive intervention and by which approaches elderly with different health risks could be reached. In several stages a specific motivational material was developed. Afterwards two different approaches to the elderly (general practice, health insurance) were tested and evaluated considering its (cost) effectiveness.

[Costs of a guideline-based treatment of patients with chronic hepatitis C in Germany]. / Kosten einer leitliniengerechten Versorgung von Hepatitis-C-Patienten in Deutschland.

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 €â€Š302.75 and monitoring accounts for €â€Š596 to €â€Š1173. Dual therapy with pegylated interferon and ribavirin results in average costs of €â€Š7709 to €â€Š34 692. Total costs of a guideline-based treatment range between €â€Š8,608 and €â€Š36 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 €â€Š43 280 respectively €â€Š54 844. Costs for Boceprevir treatment range from €â€Š34 143 to €â€Š60 990. Due to increasing costs, health-economic evaluations gain significant relevance and should be considered when implementing new treatment strategies.

[Health economic evaluation of health promotion - the example "fit for pisa"]. / Gesundheitsökonomische Evaluation der Gesundheitsförderung - am Beispiel "fit für pisa"

The increasing prevalence of risk factors associated with physical inactivity lead to an economic burden on society. The article uses the example of the prevention measure "fit for pisa" to investigate to what extent a full economic evaluation can provide a basis for decision-makers. The intervention integrated the daily physical education at 5 primary schools in Göttingen for the entire school term. The study is intended to provide information on short- and long-term potential savings. A process analysis identified the prevention performance from a societal perspective. Resource consumption was recorded in (partly) standardisedform and evaluated and also revealed the need for investment in sports halls with capacity to expand the programme to all primary schools in Göttingen. In the routine the implementation costs of half-day schools are 619 € per student year; for all-day schools 236 € per student year. The consideration of the short-term outcomes shows that TV viewing has decreased and physical activity has been strongly encouraged. The active life style promotion has shown an improvement on BMI in the medium-term. On the basis of a decision analytical model, a cost-benefit analysis of the program over the life course will be undertaken.

[Costs of guideline-based treatment of hepatitis B patients in Germany]. / Kosten einer leitliniengerechten Versorgung von Hepatitis-B-Patienten in Deutschland.

The costs of guideline-based treatment are unknown for most diseases. This also applies for economically significant infectious diseases like viral hepatitis and HIV. On the basis of the "German Guidelines for the Management of HBV Infection" from 2011 patients were grouped into HBsAg-positive, immuntolerant and chronic hepatitis patients with and without cirrhosis. Costs were divided in baseline diagnostics, monitoring and medical treatment according to the guideline. The calculation was modelled for a period of five years. Costs for virological diagnostics and imaging account for a large proportion of diagnostic costs. The main cost factors are expenses for pharmaceutical treatment with interferon or HBV polymerase inhibitors. On the assumption that only 25 % of the infected patients are diagnosed, 5-year total costs in Germany account for more than 2.5 billion Euros. Therefore, chronic hepatitis B is a disease with a very high economic burden. The aim of a guideline treatment is to prevent the development of cirrhosis with all its complications as well as the development of liver-cell carcinoma. Prophylactic vaccination against hepatitis B should be advised also considering the potential economic impact.

[Memorandum prevention research - research areas and methods]. / Memorandum zur Präventionsforschung - Themenfelder und Methoden (Langfassung).

From 2004 to 2012, the German Ministry of Education and Research (BMBF) established its first funding programme for the promotion of prevention research. 60 projects on primary prevention and health promotion and the meta-project entitled "Cooperation for Sustainable Prevention Research" (KNP) received BMBF grants under this programme during this period. The experience and knowledge gained and recommendations arising from the research funded under this programme are compiled in memorandum format. The "Memorandum on Prevention Research - Research Areas and Methods" highlights 5 research areas that are considered to be especially relevant from the perspective of the involved scientists and practice partners.The promotion of structural development and sustainability enhancement in disease prevention and health promotion are central areas that should branch out from existing nuclei of crystallization. Improving the health competence of the population and of specific subpopulations is another major area. Research in these areas should contribute to the development of theoretical concepts and to the empirical testing of these concepts. The transfer of knowledge for effective use of developed disease prevention and health promotion programmes and measures is still a scarcely researched area. Among other things, studies of the transfer of programmes from one context to another, analyses of the coop-eration between politics and science, and the continued theoretical and conceptual development of transfer research are needed. Long-term data on the effects of intervention studies are also needed for proper evaluation of sustainability. The latter dem-onstrates the importance of method development in disease prevention and health promotion research as an area that should receive separate funding and support. This research should include, in particular, studies of the efficacy of complex interventions, health economic analyses, and participative health research.

[Methods of health economic evaluation for health services research]. / Methoden der gesundheitsökonomischen Evaluation in der Versorgungsforschung.

On August 30, 2010, the German Network for Health Services Research [Deutsches Netzwerk Versorgungsforschung e. V. (DNVF e. V.)] approved the Memorandum III "Methods for Health Services Research", supported by the member societies mentioned as authors and published in this Journal [Gesundheitswesen 2010; 72: 739-748]. The present paper focuses on methodological issues of economic evaluation of health care technologies. It complements the Memorandum III "Methods for Health Services Research", part 2. First, general methodological principles of the economic evaluations of health care technologies are outlined. In order to adequately reflect costs and outcomes of health care interventions in the routine health care, data from different sources are required (e. g., comparative efficacy or effectiveness studies, registers, administrative data, etc.). Therefore, various data sources, which might be used for economic evaluations, are presented, and their strengths and limitations are stated. Finally, the need for methodological advancement with regard to data collection and analysis and issues pertaining to communication and dissemination of results of health economic evaluations are discussed.

[Newborn hearing impairment. Epidemiology and therapeutic relevance]. / Frühkindliche Hörstörungen. Epidemiologie und therapeutische Relevanz.

At last, newborn hearing screening has arrived. Hearing screening is now obligatory in Germany from 01.01.2009. Is this a reason for happiness only or will it become in those regions which do not have a setup achieved by their own initiatives for an optimal basic structure for screening and tracking, a patchwork of unorganized implementation of newborn hearing screening? By using programming models for the improvement of early detection of hearing impairment for children, the profits and debts have been identified. Multidisciplinary working groups have updated and augmented the relevant questions. At the initial start of the first screening activities it became clear that early recognition of hearing impairment in children will only be effective when this has been done in an integrated network of appropriate facilities for diagnostics and therapeutics for treatment of hearing malfunctions in children. At present tracking measures are supported in only a few federal states, while in most others both responsibilities and funding have not been organized. Some relevant cost analyses might help to avoid the coarser meanders.

[Patient education in pulmonary rehabilitation: results of an implementation study]. / Patientenschulungsprogramme in der pneumologischen Rehabilitation: Ergebnisse einer Implementationsstudie.

Patient education is considered to be a major feature of medical rehabilitation in chronic disorders. While the substantial advances in the proposition of patient education programmes in in-patient health-care remain unquestioned, there are some deficits in actually performing such programmes in clinical practice. Only few clinics adhere to the protocol and recommendations for patient education. Mostly there are deviations in the actual performance of asthma education, e. g., mixing of different education schemes or using self-developed material. The reasons why clinics hesitate to use evaluated patient education programmes is still unclear. One can assume that there are problems due to organisation, structure or staff. This project aimed at observing the process of implementation of a new asthma education programme in order to identify barriers and helpful factors for the implementation. We conducted the study in three rehabilitation centres that did not use evaluated asthma education programmes. In these clinics we implemented the new education programme. After identifying the structure of the clinic before and after the implementation, interviewing the trainers and other staff members, we could assess the specific resources and barriers. We then included these aspects into recommendations for implementation. The most important barriers we found were too few staff and problems in planning the time and rooms for the programme. There was a high level of acceptance among all staff members and patients. The entire programme causes costs of 97 euro per patient. The costs at the beginning of the implementation were higher than those for the routine use.

[Hospitalisations for acute myocardial infarction--comparing data from three different sources]. / Stationäre Behandlung des Akuten Myokardinfarktes--ein Vergleich unterschiedlicher Datenquellen.

OBJECTIVES: The aim of this study is to compare information on hospitalisations for acute myocardial infarction (AMI) from three different sources. METHODS: (A) The national hospital discharge statistics, covering all hospitalisations in Germany, is representative for this population. However, the information is limited, as data are collected case-related containing only few characteristics. (B) In contrast, claims data of sickness funds can be analysed longitudinally and contain more characteristics. The data have to be collected from single sickness funds. As for the data from registries (C) these data cannot be assumed to be representative. RESULTS: Data from the included sickness fund showed good consistency when compared to data from the national hospital discharge statistics regarding most, but not all, results. Comparisons with the register in Augsburg lead to divergent results regarding case fatality rates and rates of utilisation of technologies. CONCLUSIONS: None of the three sources can be considered ideal. Part of the differences could be explained by methodological and regional effects. More insight could be gained by comparing data at the individual level. According to recent legislation, data from all statutory sickness funds are supposed to be merged. This would simplify such comparisons and most likely would allow for more valid information regarding the incidence and treatment of AMI and many other diseases.

[Comments by the Working Group for Methods of Economic Evaluation in Health Care (AG MEG) to IQWiG's Draft Guidelines "Methods for Assessment of the Relation of Benefits to Costs in the German Statutory Health Care System"]. / Stellungnahme der AG Methoden der gesundheitsökonomischen Evaluation (AG MEG) zu dem Methodenpapier "Methodik für die Bewertung von Verhältnissen zwischen Nutzen und Kosten im System der deutschen gesetzlichen Krankenversicherung" des Instituts für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG).

Since the coming into force of the GKV-Wettbewerbsstärkungsgesetz ("Act to strengthen competition in the statutory health insurance system") in April 2007, the Gemeinsame Bundesausschuss (G-BA "Federal Joint Committee") can commission the Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG--Institute for Quality and Efficiency in Health Care") with the assessment of costs and benefits of drugs. In January 2008, IQWiG published a working document for consultation describing the proposed methods for carrying out those evaluations. This commentary by the AG Methoden der Gesundheitsökonomischen Evaluation (AG MEG--"Working Group for methods of economic evaluation in health care") provides a critical appraisal and recommendations for the further development of IQWIG's draft guidelines. The core statements of the commentary are as follows: (1) The draft guidelines are unbalanced. Instead of providing comprehensive methodological guidance for health technology assessment, which is the actual task of IQWiG, they deal predominantly with the methods of technology appraisal which is in the responsibility of the decision-making bodies, i.e. of the G-BA and the Spitzenverband Bund der Krankenkassen ("Central Federal Association of Health Insurance Funds"). (2) IQWiG intends to compare the cost-effectiveness of alternative treatment options only within a given therapeutic area. The rationale for this restriction is not clear, as the decision-makers have to determine ceiling prices across therapeutic areas and diseases and effectively the overall volume of health care expenditure, as well. (3) IQWiG aims at carrying out an economic evaluation only if in a preceding benefit assessment a drug has been judged to be superior. Therefore, it has to be assured that the benefit assessment is performed in such a way that its results may be used for the economic assessment. This requires the application of summary scores for the joint measurement of multidimensional endpoints (as, e.g., QALYs), to evaluate community effectiveness instead of efficacy, and to choose a time horizon that is sufficiently long to reflect any differences in the health benefits between the technologies being compared. Furthermore, the comment hints at some additional problems embodied in the draft guidelines and a number of key methodological issues which are not discussed at all in the working document. In summary, the methods currently proposed by IQWiG are not up to the task of conducting economic evaluations. It is strongly recommended to perform a public consultation process for the revised draft guidelines anew.

Hand hygiene in intensive care units: a matter of time?

BACKGROUND: Healthcare-associated infections are a frequent threat to patient safety and cause significant disease burden. The most important single preventive measure is hand hygiene (HH). Barriers to adherence with HH recommendations include structural aspects, knowledge gaps, and organizational issues, especially a lack of time in daily routine. AIM: To determine the number of hand hygiene opportunities (HHOs), compliance rates, and time spent on hand hygiene in intensive care units (ICUs). METHODS: We conducted an observational study in two ICUs to determine the average number of HHOs per patient. Documentation was based on the World Health Organization concept of 'five moments for hand hygiene'. HHOs were collected in 12 patient rooms for 12h each. FINDINGS: On average, 134 (internal ICU) and 182 (surgical ICU) HHOs per patient were observed during the 12h observation period. Overall HH compliance was 42.6%. Considering additional HHOs during the night shift, we estimated 218 (internal ICU) and 271 (surgical ICU) HHOs per patient-day. The average duration of hand disinfection was 7.6s. The time spent on HH was 8.3 (internal ICU) and 11.1 (surgical ICU) min during the day shift for each patient for all healthcare workers (nurses: 6.9min in the internal ICU and 8.3min in the surgical ICU). If nurses fully complied with guidelines, 58.2 (internal ICU) and 69.8 (surgical ICU) min would be spent on HH for each patient during the day shift. CONCLUSION: Complying with guidelines is time-consuming. Sufficient time for HH should be considered in staff planning.

Psychosocial determinants of self-reported hand hygiene behaviour: a survey comparing physicians and nurses in intensive care units.

BACKGROUND: Research applying psychological behaviour change theories to hand hygiene compliance is scarce, especially for physicians. AIM: To identify psychosocial determinants of self-reported hand hygiene behaviour (HHB) of physicians and nurses in intensive care units (ICUs). METHODS: A cross-sectional survey using a self-administered questionnaire that applied concepts from the Health Action Process Approach on hygienic hand disinfection was conducted in 10 ICUs and two haematopoietic stem cell transplantation units at Hannover Medical School, Germany. Self-reported compliance was operationalized as always disinfecting one's hands when given tasks associated with risk of infection. Using seven-point Likert scales, behavioural planning, maintenance self-efficacy and action control were assessed as psychological factors, and personnel and material resources, organizational problems and cooperation on the ward were assessed as perceived environmental factors. Multiple logistic regression analysis was employed. FINDINGS: In total, 307 physicians and 348 nurses participated in this study (response rates 70.9% and 63.4%, respectively). Self-reported compliance did not differ between the groups (72.4% vs 69.4%, P = 0.405). While nurses reported stronger planning, self-efficacy and action control, physicians indicated better personnel resources and cooperation on the ward (P < 0.02). Self-efficacy [odds ratio (OR) 1.4, P = 0.041], action control (OR 1.8, P < 0.001) and cooperation on the ward (OR 1.5, P = 0.036) were positively associated with HHB among physicians, but only action control was positively associated with HHB among nurses (OR 1.6, P < 0.001). CONCLUSION: The associations between action control (self-regulatory strategies where behaviour is evaluated continuously and automatically against guidelines) and compliance indicate that HHB is a habit in need of self-monitoring. The fact that perceived cooperation on the ward was the only environmental correlate of HHB among physicians stresses the importance of team-directed interventions.

2-Chloroethyl (methylsulfonyl)methanesulfonate and related (methylsulfonyl)methanesulfonates. Antineoplastic activity in vivo.

2-Haloethyl and ethyl (methylsulfonyl)methanesulfonates were prepared via sulfene intermediates. 2-Chloroethyl (methylsulfonyl)methanesulfonate is highly active against P388 leukemia in vivo; the majority of leukemic mice treated with this compound at 50 mg/kg per day, qd 1-5, survived more than 30 days and about 37% survived for more than 60 days. 2- Fluoroethyl (methylsulfonyl)methanesulfonate is also highly effective against P388 cells in vivo, but it is more toxic. Other (methylsulfonyl)methanesulfonate esters are more active than the analogous methanesulfonates and chloromethanesulfonates .

Terminal bifunctional retinoids. Synthesis and evaluations related to cancer chemopreventive activity.

Retinoids that have two functional groups at the side-chain terminus have been synthesized. The two terminal functional groups are combinations of the carboxyl, carbethoxy, and N-(ethylamino)carbonyl groups. The synthesis route is based on the sodium amide catalyzed condensation of (E,E)-beta-ionylideneacetaldehyde with diethyl isopropylidenemalonate. Ethyl 14-carboxyretinoate (6), the initial bifunctional analogue, undergoes isomerization in unbuffered aqueous ethanol and reaches a state of equilibrium with ethyl 14-carboxy-13-cis-retinoate. Both of the possible amide-esters and amide-acids were obtained. The structures of the isomeric bifunctional analogues were established by studies of nuclear Overhauser effects. The bifunctional analogues induce differentiation of mouse embryonal carcinoma cells, and those analogues that have a free carboxyl group bind to cellular retinoic acid binding protein.