[Fecal Microbiota Transfer (FMT) in Germany - Status and Perspective]. / Fäkaler Mikrobiota-Transfer (FMT) in Deutschland ­ Status und Perspektive.

INTRODUCTION: Fecal microbiota transfer (FMT) is a treatment to modulate the gastrointestinal microbiota. Its use in recurrent Clostridioides difficile infection (rCDI) is established throughout Europe and recommended in national and international guidelines. In Germany, the FMT is codeable in the hospital reimbursement system. A comprehensive survey on the frequency of use based on this coding is missing so far. MATERIAL AND METHODOLOGY: Reports of the Institute for Hospital Remuneration (InEK), the Federal Statistical Office (DESTATIS), and hospital quality reports 2015-2021 were examined for FMT coding and evaluated in a structured expert consultation. RESULTS: Between 2015 and 2021, 1,645 FMT procedures were coded by 175 hospitals. From 2016 to 2018, this was a median of 293 (274-313) FMT annually, followed by a steady decline in subsequent years to 119 FMT in 2021. Patients with FMT were 57.7% female, median age 74 years, and FMT was applied colonoscopically in 72.2%. CDI was the primary diagnosis in 86.8% of cases, followed by ulcerative colitis in 7.6%. DISCUSSION: In Germany, FMT is used less frequently than in the European comparison. One application hurdle is the regulatory classification of FMT as a non-approved drug, which leads to significantly higher costs in manufacturing and administration and makes reimbursement difficult. The European Commission recently proposed a regulation to classify FMT as a transplant. This could prospectively change the regulatory situation of FMT in Germany and thus contribute to a nationwide offer of a therapeutic procedure recommended in guidelines.

[Need for improvement in the care of patients with Clostridioides difficile infections (CDI) - expert opinion in international comparison]. / Verbesserungsbedarf in der Versorgung von Patienten/-innen mit Clostridioides-difficile-lnfektionen (CDI) ­ Experten/-innenmeinung im internationalen Vergleich.

INTRODUCTION: Clostridioides difficile infection (CDI), as a nosocomial disease, is associated with high morbidity and mortality. Even though the incidence of CDI has been declining in Germany in recent years, the individual infection may pose a medical challenge despite therapeutic advances. The aim here is to clarify which gaps practitioners consider to be particularly serious in care and in the existing evidence base. METHODS: In a moderated workshop of German CDI experts the topics considered as relevant were identified. A survey already conducted in five other countries (Australia, France, Great Britain, Canada, and Italy) was adapted and processed by 27 practitioners. During the evaluation, the topics perceived as particularly important were identified, the statements of the specialist groups were compared and changes in opinion were considered. RESULTS: 27 fully completed questionnaires were evaluated. The need for improvement was primarily seen in the prevention of CDI recurrences (74.1%) and the treatment of recurrences (55.6%). Evidence deficits were noted in the treatment of recurrences (55.6%) and identification of risk factors for recurrences (48.1%). Improving care via fecal microbiota transfer (FMT) was named by 70.4%. For guidelines, more clarity (48.1%) and more regular updates (40.7%) were desired. For patients, better education on appropriate antibiotic use (52.0%) and choice of FMT were desired (48.1%). SUMMARY: The German expert view and the international assessment is similar, when asked about the need for improvement in care and evidence gaps in the treatment of patients with CDI: The focus is on prevention and therapy of recurrent CDI. The problem of access to FMT is a German peculiarity that seems to need improvement.

Trends in the epidemiology of Clostridioides difficile infection in Germany.

PURPOSES: Despite reports of a declining incidence over the last decade, Clostridioides difficile infection (CDI) is still considered the most important healthcare-associated causes of diarrhea worldwide. In Germany, several measures have been taken to observe, report, and influence this development. This report aims to analyze the development of hospital coding for CDI in Germany over the last decade and to use it to estimate the public health burden caused by CDI. METHODS: Reports from the Institute for Hospital Remuneration Systems, German Federal Statistical Office (DESTATIS), the Robert-Koch-Institute (RKI), Saxonian authorities and hospital quality reports during 2010-2021 were examined for CDI coding and assessed in a structured expert consultation. Analysis was performed using 2019 versions of Microsoft Excel® and Microsoft Access®. RESULTS: Peaks of 32,203 cases with a primary diagnosis (PD) of CDI and 78,648 cases with a secondary diagnosis (SD) of CDI were observed in 2015. The number of cases had decreased to 15,412 PD cases (- 52.1%) and 40,188 SD cases (- 48.9%) by 2021. These results were paralleled by a similar decline in notifiable severe cases. However, average duration of hospitalization of the cases remained constant during this period. CONCLUSIONS: Hospital coding of CDI and notification to authorities has approximately halved from 2015 to 2021. Potential influential factors include hospital hygiene campaigns, implementation of antibiotic stewardship programs, social distancing due to the COVID-19 pandemic, and a decrease in more pathogenic subtypes of bacteria. Further research is necessary to validate the multiple possible drivers for this development.

[Retrospective cross-sectional study based on nationwide data of drug prescriptions and contractional data of outpatient offices regarding Morbus Wilson's disease]. / Retrospektive Querschnittsstudie von bundesweiten Arzneiverordnungsdaten und vertragsärztlichen Abrechnungsdaten von Morbus Wilson.

INTRODUCTION: In this article, the prevalence of the Morbus Wilson disease in Germany is determined. This is based on nationwide data of drug prescriptions and contractional data of outpatient offices. The prevalence is set in ratio to the found prevalence of prescriptions in Germany. METHOD: The descriptive evaluation is based on the database of the Central Research Institute of Ambulatory Health Care (Zi) in Germany. Additionally, data of the Federal Office of Statistics regarding inpatient treatment are available. RESULTS: It can be seen that there is a notable difference between the prevalence of patients undergoing therapy and the patients with verified diagnoses. In total, prevalence is increasing. The incidence on hand and the given dynamic of the patient population could indicate that, possibly, there is an increased rate of misdiagnosis in the first year of diagnosis. According to data, the hepatic form is the more often diagnosed form. The human genetic diagnostic increases, on average, are most distinct. ATTRIBUTES: Wilson Disease, Prevalence, Incidence, Trientine, Trientintetrahydrochlorid, D-Penicillamin, Zinc acetat, Zinc.

Reperfusion therapy for ST elevation acute myocardial infarction 2010/2011: current status in 37 ESC countries.

AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred reperfusion therapy in ST-elevation myocardial infarction (STEMI). We conducted this study to evaluate the contemporary status on the use and type of reperfusion therapy in patients admitted with STEMI in the European Society of Cardiology (ESC) member countries. METHODS AND RESULTS: A cross-sectional descriptive study based on aggregated country-level data on the use of reperfusion therapy in patients admitted with STEMI during 2010 or 2011. Thirty-seven ESC countries were able to provide data from existing national or regional registries. In countries where no such registries exist, data were based on best expert estimates. Data were collected on the use of STEMI reperfusion treatment and mortality, the numbers of cardiologists, and the availability of PPCI facilities in each country. Our survey provides a brief data summary of the degree of variation in reperfusion therapy across Europe. The number of PPCI procedures varied between countries, ranging from 23 to 884 per million inhabitants. Primary percutaneous coronary intervention and thrombolysis were the dominant reperfusion strategy in 33 and 4 countries, respectively. The mean population served by a single PPCI centre with a 24-h service 7 days a week ranged from 31 300 inhabitants per centre to 6 533 000 inhabitants per centre. Twenty-seven of the total 37 countries participated in a former survey from 2007, and major increases in PPCI utilization were observed in 13 of these countries. CONCLUSION: Large variations in reperfusion treatment are still present across Europe. Countries in Eastern and Southern Europe reported that a substantial number of STEMI patients are not receiving any reperfusion therapy. Implementation of the best reperfusion therapy as recommended in the guidelines should be encouraged.

Adjuvant treatment of high-risk melanoma - cost-effectiveness analysis of treatment options for BRAF 600 mutated tumors.

INTRODUCTION: Until recently, adjuvant treatment options for higher stage resectable cutaneous melanoma were limited. Two studies with a similar set-up, published 2017, led to registration of targeted therapy for BRAF-mutated melanoma with dabrafenib and trametinib as well as of the immunotherapy with nivolumab irrespective of BRAF-mutation status. Both options have been positively assessed in Germany since 2019 for the adjuvant treatment of BRAF-V600 mutated melanoma. This study evaluates the cost-effectiveness of both treatment alternatives (dabrafenib/trametinib and nivolumab) against observation as a comparative therapy from the perspective of German statutory health funds. METHODS: Partitioned survival analysis based on published survival curves for the investigated treatment options was used for a cohort model for the health states relapse free survival, progression, and death. The partitioned survival analysis approach was based on the survival curves published for the key studies Combi AD and Checkmate-238. The modelling was performed for the remaining lifetime for a cohort with starting age of 50 years. For extrapolation of the survival curves, convergence to general population mortality rates was assumed in the long term. Within the progression state, a Markov model uses three levels of progressions (locoregional, distant metastases with 1st and 2nd line treatment). Lifetime treatment costs were calculated using the German statutory health fund reimbursement scheme. Quality adjusted life years (QALYs) associated to the health states were adopted from previously published utilities based on the Combi AD study. RESULTS: The treatment with dabrafenib/trametinib yielded an increase in quality adjusted life years of 2.28 QALY at an incremental lifetime cost of 86.1 T€. The incremental cost effectiveness ratio of dabrafenib/trametinib and nivolumab was comparable with 37.8 T€/QALY and 30.0 T€/QALY, respectively. Several sensitivity analyses proved the result to be insensitive. General model parameters like discount rate and length of the time horizon had stronger influence. For nivolumab, the model showed lower discounted lifetime costs (118.1 T€) compared to dabrafenib/trametinib [155.1 T€], associated with a lower gain in QALYs (1.64 years) compared to observation. CONCLUSION: Both dabrafenib/trametinib and nivolumab turned out to be cost effective within internationally accepted Incremental Cost Effectiveness Ratio (ICER) thresholds with comparable cost effectiveness ratios.

Cost-effectiveness of a photopethysmographic procedure for screening for atrial fibrillation in 6 European countries.

BACKGROUND: Strokes cause an estimated annual health care burden of 170 billion euros across Europe. Atrial fibrillation is one of the major risk factors for stroke and increases the individual risk 4.2-fold. But prevention with anticoagulants may reduce this risk by 70%. Screening methods are employed to detect previously undetected atrial fibrillation. Screening studies in various European countries show a high degree of undetected atrial fibrillation. This study aims to assess the cost-effectiveness of systematic screening with a smartphone application, named Preventicus Heartbeats. It is a hands-on screening tool for use on smartphone to diagnose AF with high sensitivity and specificity. METHODS: A previously published model for calculating screening cost-effectiveness was extended to 6 European countries covering a wide range in terms of treatment costs and epidemiologic parameters. RESULTS: The use of screening lowers the cost per case in countries with comparatively high levels of health care costs (Switzerland: -€75; UK: -€7). Moderate higher costs per case were observed in 4 countries (Greece: €6; Netherlands: €15). Low levels of health care costs result in less or no potential for further cost reduction (Poland: €20; Serbia: €33). In all countries considered, the model showed an increase in effectiveness measures both in the number of strokes avoided and the quality adjusted life years. The number of strokes avoided per 1000 participants ranged from 2.52 (Switzerland) to 4.44 (Poland). Quality-adjusted life-years per case gained from screening ranged from 0.0105 (Switzerland) to 0.0187 (Poland). The screening procedure dominated in two countries (Switzerland, UK). For the remaining countries, the incremental cost effectiveness ratio ranged from €489/QALY (Greece) to €2548/QALY (Serbia). CONCLUSION: The model results showed a strong dependence of the results on the country-specific costs for stroke treatment. The use of the investigated screening method is close to cost-neutral or cost-reducing in the Western European countries and Greece. In countries with low price levels, higher cost increases due to AF screening are to be expected. Lower costs of anticoagulation, which are expected due to the upcoming patent expiry of direct anticoagulants, have a positive effect on the cost result.

The Ecological Footprint of COVID-19 mRNA Vaccines: Estimating Greenhouse Gas Emissions in Germany.

Compared to the medical, economic and social implications of COVID-19 vaccinations, little attention has been paid to the ecological balance to date. This study is an attempt to estimate the environmental impact of two mRNA vaccines in terms of CO2 equivalents with respect to their different freezing strategies and supply chain organization. Although it is impossible to accurately calculate the actual environmental impact of the new biochemical synthesis technology, it becomes apparent that transport accounts for up to 99% of the total carbon footprint. The emissions for air freight, road transportation and last-mile delivery are nearly as 19 times the emissions generated from ultra-deep freeze technologies, the production of dry ice, glass and medical polymers for packaging. The carbon footprint of a single mRNA vaccine dose injected into a patient is about 0.01 to 0.2 kg CO2 equivalents, depending on the cooling technology and the logistic routes to the vaccination sites in Germany.

A cost-effectiveness analysis model of Preventicus atrial fibrillation screening from the point of view of statutory health insurance in Germany.

BACKGROUND: With atrial fibrillation (AF) the risk of stroke is 4.2-fold increased to a comparable population without AF. This risk decreases by up to 70% if AF is detected early enough and effective stroke preventive measures are taken as recommended by international guidelines. Long-term studies found large number of subjects with undiagnosed AF. Preventicus Heartbeats" is a hands-on screening tool for use on smartphone to diagnose AF with high sensitivity and specificity. The aim of this study is to research the cost-effectiveness of systematic screening for AF with this smartphone application. METHOD: Employing a Markov model we analysed the cost-effectiveness of the "Preventicus Heartbeats" screening for Germany, i.e. from the perspective of German statutory sick funds. RESULTS: For a cohort of 10,000 insured 75-year-old the use of the diagnostic app could avoid 60 strokes in the remaining lifetime thereof 32 strokes in the next four years. Former models have applied similar cohorts. The same cohort showed an increase in quality-adjusted life years (QALY) in the remaining lifetime of 165 QALYs in the scenario with screening versus. without screening and a decrease in discounted lifetime costs (including risk compensation effects) of €129 per participant (€148 for male, €114 for female participants). CONCLUSIONS: The modelling demonstrates the health benefits and economic effects of an implementation of a systematic screening on AF with "Preventicus Heartbeats", given the perspective of the German payer, the statutory health care system.

Short term cost effectiveness of a regional myocardial infarction network.

AIMS: Myocardial infarction networks have been shown to improve guideline adherent therapy and outcomes in patients presenting with acute ST-elevation myocardial infarction (STEMI). Our objective was to assess the short term cost effectiveness of a network structure. METHODS AND RESULTS: Outcome data and reimbursement data for the index hospital stay were gathered in consecutive patients with acute STEMI (n = 536) admitted to any of the hospitals in a 350.000 inhabitant rural network area during the years 2002 (n = 185), 2005 (n = 163) and 2008 (n = 188). Network structure was established between 2002 and 2005 aiming for identical treatment of all acute STEMI patients during 24 h/7d a week with primary angioplasty. Patient baseline characteristics in the different years were quite comparable. From 2002 to 2005 regional hospital mortality in STEMI patients decreased from 16% to 9%. Lower mortality under network conditions was confirmed in 2008. Reimbursement data of different years were standardized to exclude effects not induced by the network. The mean initial costs per saved live during the index stay were €7727 with a 95%-confidence interval of €-3.500 to €36.700 (referenced to the German reimbursement in 2005). CONCLUSION: The short term cost effectiveness of a myocardial infarction network organisation is within well accepted boundaries under conditions of the German reimbursement system.