Jona T. Stahmeyer

High prevalence of hepatitis markers in immigrant populations: a prospective screening approach in a real-world setting.

Background Immigrant populations are believed to be more frequently infected with hepatitis viruses. However, limited unbiased data are available on immigrants outside of academic centres. Therefore, the aim of this study was to perform large-scale screening for hepatitis markers in primary care centres treating mainly individuals with a migrational background in Germany. Methods Between November 2010 and January 2012, we prospectively screened 1313 individuals treated by general practitioners at eight primary care centres in North-western Germany. Patients were eligible if they or their parents were not born in Germany. Serological screening for hepatitis B core protein antibodies, hepatitis B surface antigens (HBsAgs), and anti-hepatitis C virus antibodies was performed in each individual. HBsAg-positive and anti-hepatitis C virus-positive patients were further tested for molecular markers of viral replication. Results The mean age was 49.1±15.8 years. Of the patients, 45.7% were male; 87.3% had migrated to Germany from the Eastern Mediterranean area and 12.0% from Eastern Europe. Of the patients, 32.5% tested positive for hepatitis B core protein antibodies. HBsAgs were found in 3.6% of patients. Overall, hepatitis B virus DNA was detected in 2.2% of patients. Markers for hepatitis C virus infection were found in an almost similar high frequency (1.9%). Individuals with migrational background showed significant deficits in knowledge on general routes of transmission. Conclusion Hepatitis virus infections are indeed significantly more prevalent in immigrant populations as compared with the general German population. These data underline the importance of introducing screening programs in this particular risk group.

Comparison of tools for assessing the methodological quality of primary and secondary studies in health technology assessment reports in Germany.

Health care policy background Findings from scientific studies form the basis for evidence-based health policy decisions. Scientific background Quality assessments to evaluate the credibility of study results are an essential part of health technology assessment reports and systematic reviews. Quality assessment tools (QAT) for assessing the study quality examine to what extent study results are systematically distorted by confounding or bias (internal validity). The tools can be divided into checklists, scales and component ratings. Research questions What QAT are available to assess the quality of interventional studies or studies in the field of health economics, how do they differ from each other and what conclusions can be drawn from these results for quality assessments? Methods A systematic search of relevant databases from 1988 onwards is done, supplemented by screening of the references, of the HTA reports of the German Agency for Health Technology Assessment (DAHTA) and an internet search. The selection of relevant literature, the data extraction and the quality assessment are carried out by two independent reviewers. The substantive elements of the QAT are extracted using a modified criteria list consisting of items and domains specific to randomized trials, observational studies, diagnostic studies, systematic reviews and health economic studies. Based on the number of covered items and domains, more and less comprehensive QAT are distinguished. In order to exchange experiences regarding problems in the practical application of tools, a workshop is hosted. Results A total of eight systematic methodological reviews is identified as well as 147 QAT: 15 for systematic reviews, 80 for randomized trials, 30 for observational studies, 17 for diagnostic studies and 22 for health economic studies. The tools vary considerably with regard to the content, the performance and quality of operationalisation. Some tools do not only include the items of internal validity but also the items of quality of reporting and external validity. No tool covers all elements or domains. Design-specific generic tools are presented, which cover most of the content criteria. Discussion The evaluation of QAT by using content criteria is difficult, because there is no scientific consensus on the necessary elements of internal validity, and not all of the generally accepted elements are based on empirical evidence. Comparing QAT with regard to contents neglects the operationalisation of the respective parameters, for which the quality and precision are important for transparency, replicability, the correct assessment and interrater reliability. QAT, which mix items on the quality of reporting and internal validity, should be avoided. Conclusions There are different, design-specific tools available which can be preferred for quality assessment, because of its wider coverage of substantive elements of internal validity. To minimise the subjectivity of the assessment, tools with a detailed and precise operationalisation of the individual elements should be applied. For health economic studies, tools should be developed and complemented with instructions, which define the appropriateness of the criteria. Further research is needed to identify study characteristics that influence the internal validity of studies.

Cost of treating hepatitis C in Germany: a retrospective multicenter analysis.

Background Viral hepatitis is major a public health problem affecting millions of people worldwide. Estimates assume 400 000–500 000 people chronically infected with hepatitis C virus (HCV) in Germany. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. The aim of the study was to assess the costs for treating patients with chronic HCV in Germany. Methods We conducted a retrospective multicenter observational study. The design was approved by an ethics committee, and patients were asked for their informed consent. Patients were grouped in four different health states. Healthcare utilization data were extracted from doctor files of six medical centers in Germany. Results Data of 315 patients with chronic HCV were analyzed. The mean age was 49.4 years, 57.5% were male and 67.9% had a genotype 1 infection. The most common routes of transmission were injection drug use (39.0%) and infection through blood products (15.9%). The average total cost was &OV0556;19 147 including ambulatory care and diagnostics (&OV0556;1686), pharmaceuticals (&OV0556;14 875), inpatient care (&OV0556;1293), and sick leave (&OV0556;1293). For patients in stable health states (mild and moderate HCV, compensated cirrhosis), costs did not differ significantly and were mainly influenced by antiviral treatment. For patients with decompensated cirrhosis, inpatient care accounted for the largest part of the costs. Conclusion Treatment of HCV patients involves high costs, mainly associated with the length of antiviral therapy. Viral eradication can prevent severe disease stages, which are associated with high costs. It is necessary to follow current guidelines and monitor patients closely to avoid unnecessary costs.

Cost-Effectiveness of Treating Hepatitis C with Sofosbuvir/Ledipasvir in Germany.

Background Infections with the hepatitis C virus (HCV) are a global public health problem. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. Newly introduced direct acting antivirals, especially interferon-free regimens, have improved rates of sustained viral response above 90% in most patient groups and allow treating patients who were ineligible for treatment in the past. These new regimens have replaced former treatment and are recommended by current guidelines. However, there is an ongoing discussion on high pharmaceutical prices. Our aim was to assess the long-term cost-effectiveness of treating hepatitis C genotype 1 patients with sofosbuvir/ledipasvir (SOF/LDV) treatment in Germany. Material and Methods We used a Markov cohort model to simulate disease progression and assess cost-effectiveness. The model calculates lifetime costs and outcomes (quality-adjusted life years, QALYs) of SOF/LDV and other strategies. Patients were stratified by treatment status (treatment-naive and treatment-experienced) and absence/presence of cirrhosis. Different treatment strategies were compared to prior standard of care. Sensitivity analyses were performed to evaluate model robustness. Results Base-case analyses results show that in treatment-naive non-cirrhotic patients treatment with SOF/LDV dominates the prior standard of care (is more effective and less costly). In cirrhotic patients an incremental cost-effectiveness ratio (ICER) of 3,383 €/QALY was estimated. In treatment-experienced patients ICERs were 26,426 €/QALY and 1,397 €/QALY for treatment-naive and treatment-experienced patients, respectively. Robustness of results was confirmed in sensitivity analyses. Conclusions Our analysis shows that treatment with SOF/LDV is cost-effective compared to prior standard of care in all patient groups considering international costs per QALY thresholds.

Outcomes, costs and cost-effectiveness of treating hepatitis C with direct acting antivirals

Hepatitis C is a global public health burden. Long-term consequences are the development of liver cirrhosis and hepatocellular carcinoma. Introduction of different direct acting antivirals targeting the hepatitis C proteins has considerably increased rates of sustained viral response. First active substances introduced in 2011 were NS3/4A protease inhibitors telaprevir and boceprevir. In 2013/2014 the second generation of direct acting antivirals sofosbuvir, simeprevir, daclatasvir, ledipasvir and 3D therapy containing ombitasvir/paritaprevir/ritonavir and dasabuvir followed. This review focuses on treatment outcomes and costs of introduced direct acting antivirals. We provide an overview on SVR-rates in clinical trials and clinical practice, treatment costs in different countries as well as results of cost-effectiveness analyses for different treatment strategies.

Resource Utilisation and Costs of Depressive Patients in Germany: Results from the Primary Care Monitoring for Depressive Patients Trial

Background. Depression is the most common type of mental disorder in Germany. It is associated with a high level of suffering for individuals and imposes a significant burden on society. The aim of this study was to estimate the depression related costs in Germany taking a societal perspective. Materials and Methods. Data were collected from the primary care monitoring for depressive patients trial (PRoMPT) of patients with major depressive disorder who were treated in a primary care setting. Resource utilisation and days of sick leave were observed and analysed over a 1-year period. Results. Average depression related costs of €3813 were calculated. Significant differences in total costs due to sex were demonstrated. Male patients had considerable higher total costs than female patients, whereas single cost categories did not differ significantly. Further, differences in costs according to severity of disease and age were observed. The economic burden to society was estimated at €15.6 billion per year. Conclusion. The study results show that depression poses a significant economic burden to society. There is a high potential for prevention, treatment, and patient management innovations to identify and treat patients at an early stage.

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.

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 ones 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.

High resource utilization in liver transplantation—how strongly differ costs between the care sectors and what are the main cost drivers?: a retrospective study

To control treatment pathways of transplant patients across healthcare sectors, a profound knowledge of the underlying cost structure is necessary. The aim of this study was to analyze the resource utilization of patients undergoing liver transplantation. Data on resource utilization for 182 liver‐transplanted patients was investigated retrospectively. The observational period started with the entry on the waiting list and ended up to 3 years after transplantation. Median treatment cost was 144 424€. During waiting time, median costs amounted to 9466€; 72% of costs were attributed to inpatient care, 3% to outpatient care, and 26% to pharmaceuticals. During the first year after transplantation, median costs of 105 566€ were calculated; 83% were allocated for inpatient and 1% outpatient care, 14% for drugs, and 1% for rehabilitative care. During follow‐up after the first year of transplantation, median costs amounted to 20 115€; 75% of these were caused by pharmaceuticals, 21% by inpatient, 4% by outpatient, and <1% by rehabilitative services. Subgroup analyses (e.g., for labMELD scores) were done. Costs incurred by inpatient care and pharmaceuticals are the dominating cost factors. These findings encourage a debate on challenges and improvements for cost‐efficient clinical management between different healthcare sectors.

Economic study of the value of expanding HCV treatment capacity in Germany

Background Todays highly efficacious, low-toxicity interferon-free treatment regimens for chronic hepatitis C virus (HCV) can cure most patients with HCV in 12–24 weeks. The aim of this study was to understand how the introduction of shorter duration treatment regimens for HCV will impact the capacity for treatment and value to society. Methods A Markov model of HCV transmission and progression was constructed, incorporating nationally representative data on HCV prevalence, incidence and progression; mortality, treatment costs, medical expenditures, employment probabilities and disability payments in Germany. The model was stratified by HCV genotype and exposure route (1-time healthcare exposure, injection drug use and sexual activity). Treatment scenarios were based on German treatment guidelines and projected treatment capacity. The impact of different treatment scenarios on disease transmission and prevalence, quality-adjusted life years (QALYs), treatment costs, medical expenditures, employment and disability expenditures was calculated. Results Depending on their adoption profile, new treatment regimens and protocols introduced over the next several years will increase HCV treatment capacity in Germany by 8–30%, reducing disease transmission and prevalence, increasing QALYs and adding €94–310 million in discounted social value (QALYs plus medical savings net of treatment costs) over a 30-year horizon. Additional social value in the form of higher employment and lower disability would also result. Conclusions The introduction of shorter HCV treatment regimens and the resulting increased treatment capacity in Germany would result in large gains to society by reducing disease transmission and prevalence, resulting in longer, healthier, more productive lives for current and future generations.