Evaluation of undetected cases during the COVID-19 epidemic in Austria.

BACKGROUND: Knowing the number of undetected cases of COVID-19 is important for a better understanding of the spread of the disease. This study analyses the temporal dynamic of detected vs. undetected cases to provide guidance for the interpretation of prevalence studies performed with PCR or antibody tests to estimate the detection rate. METHODS: We used an agent-based model to evaluate assumptions on the detection probability ranging from 0.1 to 0.9. For each general detection probability, we derived age-dependent detection probabilities and calibrated the model to reproduce the epidemic wave of COVID-19 in Austria from March 2020 to June 2020. We categorized infected individuals into presymptomatic, symptomatic unconfirmed, confirmed and never detected to observe the simulated dynamic of the detected and undetected cases. RESULTS: The calculation of the age-dependent detection probability ruled values lower than 0.4 as most likely. Furthermore, the proportion of undetected cases depends strongly on the dynamic of the epidemic wave: during the initial upswing, the undetected cases account for a major part of all infected individuals, whereas their share decreases around the peak of the confirmed cases. CONCLUSIONS: The results of prevalence studies performed to determine the detection rate of COVID-19 patients should always be interpreted with regard to the current dynamic of the epidemic wave. Applying the method proposed in our analysis, the prevalence study performed in Austria in April 2020 could indicate a detection rate of 0.13, instead of the prevalent ratio of 0.29 between detected and estimated undetected cases at that time.

Economic burden of stroke: a systematic review on post-stroke care.

OBJECTIVES: Stroke is a leading cause for disability and morbidity associated with increased economic burden due to treatment and post-stroke care (PSC). The aim of our study is to provide information on resource consumption for PSC, to identify relevant cost drivers, and to discuss potential information gaps. METHODS: A systematic literature review on economic studies reporting PSC-associated data was performed in PubMed/MEDLINE, Scopus/Elsevier and Cochrane databases, Google Scholar and gray literature ranging from January 2000 to August 2016. Results for post-stroke interventions (treatment and care) were systematically extracted and summarized in evidence tables reporting study characteristics and economic outcomes. Economic results were converted to 2015 US Dollars, and the total cost of PSC per patient month (PM) was calculated. RESULTS: We included 42 studies. Overall PSC costs (inpatient/outpatient) were highest in the USA ($4850/PM) and lowest in Australia ($752/PM). Studies assessing only outpatient care reported the highest cost in the United Kingdom ($883/PM), and the lowest in Malaysia ($192/PM). Fifteen different segments of specific services utilization were described, in which rehabilitation and nursing care were identified as the major contributors. CONCLUSION: The highest PSC costs were observed in the USA, with rehabilitation services being the main cost driver. Due to diversity in reporting, it was not possible to conduct a detailed cost analysis addressing different segments of services. Further approaches should benefit from the advantages of administrative and claims data, focusing on inpatient/outpatient PSC cost and its predictors, assuring appropriate resource allocation.

Cost effectiveness of personalized treatment in women with early breast cancer: the application of OncotypeDX and Adjuvant! Online to guide adjuvant chemotherapy in Austria.

A Breast Cancer Outcomes model was developed at the ONCOTYROL research center to evaluate personalized test-treatment strategies in Austria. The goal was to evaluate the cost-effectiveness of a new 21-gene assay (ODX) when used in conjunction with the Adjuvant! Online (AO) decision aid to support personalized decisions about use of adjuvant chemotherapy in early-stage breast cancer patients in Austria. We applied a validated discrete-event-simulation model to a hypothetical cohort of 50 years old women over a lifetime horizon. The test-treatment strategies of interest were defined using three-letter acronyms. The first (second, third) letter indicates whether patients with a low (intermediate, high) risk according to AO were tested using ODX (Y yes, N no). The main outcomes were life-years gained, quality-adjusted life-years (QALYs), costs and cost effectiveness. Robustness of the results was tested in sensitivity analyses. Results were compared to a Canadian analysis conducted by the Toronto Health Economics and Technology Assessment Collaborative (THETA). Five of eight strategies were dominated (i.e., more costly and less effective: NNY, NYN, YNN, YNY, YYN). The base-case analysis shows that YYY (ODX provided to all patients) is the most effective strategy and is cost effective with an incremental cost-effectiveness ratio of 15,700 EUR per QALY gained. These results are sensitive to changes in the probabilities of distant recurrence, age and costs of chemotherapy. The results of the base-case analysis were comparable to the THETA results. Based on our analyses, using ODX in addition to AO is effective and cost effective in all women in Austria. The development of future genetic tests may require alternative or additional test-treatment strategies to be evaluated.

Cost-effectiveness of primary HPV screening for cervical cancer in Germany--a decision analysis.

OBJECTIVES: To systematically evaluate the long-term effectiveness and cost-effectiveness of HPV-based primary cervical cancer screening in the German health care context using a decision-analysis approach. METHODS: A Markov-model for HPV-infection and cervical cancer was developed for the German health care context, and applied to evaluate various screening strategies that differ by screening interval and test algorithms, including HPV-testing alone or in combination with cytology. German clinical, epidemiological, and economic data, and test accuracy data from international meta-analyses were used. Outcomes predicted included the reduction in cervical cancer cases and deaths, life expectancy and discounted incremental cost-effectiveness ratios (ICER). The analysis was performed from the perspective of the healthcare system adopting a 3% annual discount rate for costs and outcomes. Extensive sensitivity analyses were performed. RESULTS: HPV-based screening is more effective than cytology alone. It results in a 71-97% reduction in cervical cancer cases as compared to 53-93% for cytology alone. The ICER range from 2600 Euro/LYG (cytology, 5-year-interval) to 155,500 Euro/LYG (annual HPV-testing starting at age 30 years, cytology age 20-29 years). Annual cytology alone, the current recommended screening strategy in Germany, is dominated by HPV-strategies. Increasing the age at screening initiation from 20 to 25 years does not result in a relevant loss in effectiveness but results in lower costs. CONCLUSIONS: Based on our analyses, HPV-based cervical cancer screening is more effective than cytology alone and could be cost-effective if performed at intervals of two years or longer. In the German context, an optimal screening strategy may be biennial HPV screening starting at age 30 years preceded by biennial cytology for women aged 25-29 years. Longer screening intervals may be considered in low-risk women with good screening adherence and in populations with low HPV-incidence.

Long-term effectiveness and cost-effectiveness of antiviral treatment in hepatitis C.

We systematically reviewed the evidence for long-term effectiveness and cost-effectiveness of antiviral treatment in patients with chronic hepatitis C. We performed a systematic literature search on the long-term effectiveness and cost-effectiveness of AVT in hepatitis C (1990-March 2007), and included health technology assessment (HTA) reports, systematic reviews, long-term clinical trials, economic studies conducted alongside clinical trials and decision-analytic modelling studies. All costs were converted to 2005euro. Antiviral therapy with peginterferon plus ribavirin in treatment-naïve patients with chronic hepatitis C was the most effective (3.6-4.7 life years gained [LYG]) treatment and was reasonably cost-effective (cost-saving to 84 700euro/quality adjusted life years [QALY]) when compared to interferon plus ribavirin. Some results also suggest cost-effectiveness (below 8400euro/(QALY) of re-treatment in nonresponders/relapsers. Results for patients with persistently normal alanine aminotransferase (ALT) levels or with special co-morbidities (e.g. HIV) or risk profiles were rare. We conclude that antiviral therapy may prolong life, improve long-term health-related quality-of-life and be reasonably cost-effective in treatment-naïve patients with chronic hepatitis C as well as in former relapsers/nonresponders. Further research is needed in patients with specific co-morbidities or risk profiles.

[Health economics of chronic infectious diseases: the example of hepatitis C]. / Gesundheitsökonomische Aspekte chronischer Infektionskrankheiten am Beispiel der chronischen Hepatitis C.

Based on the German Hepatitis C Model (GEHMO) we developed a Hepatitis C Policy Model and applied it to the heterogeneous German hepatitis C population within the German health care context. We used Markov cohort simulation to predict absolute clinical and economic outcomes for a 20-year time horizon. For the cost-effectiveness analysis, a lifelong time horizon was used. Four different strategies were compared: (1) no antiviral treatment, (2) interferon monotherapy, (3) combination therapy with interferon plus ribavirin, and (4) combination therapy with pegylated interferon plus ribavirin. Based on our model, antiviral therapy with pegylated interferon and ribavirin could prevent about 17,000 cases of cirrhosis, 580 liver transplants, and 7,600 HCV-related deaths and is expected to save about 53,000 life years at total costs of 1.3 billion Euros within the next 20 years. Pegylated interferon plus ribavirin was the most effective treatment with an incremental cost-utility ratio of 23,000 Euros per quality-adjusted life year saved.

Fractional flow reserve for the prediction of cardiac events after coronary stent implantation: results of a multivariate analysis.

OBJECTIVE: To determine the prognostic value of fractional flow reserve (FFR) measurements after coronary stent implantation including multiple clinical and angiographic parameters collected in one centre. METHODS: 119 consecutive patients were enrolled who had a stent implanted with the use of a pressure wire as a guidewire. Patients were followed up for at least six months. Any death, myocardial infarction, and target vessel revascularisation were considered major adverse cardiac events (MACE). Multivariate logistic regression was used to determine adjusted odds ratios (OR) and 95% confidence intervals (CI) for FFR and covariates. RESULTS: Complete follow up data were available for all 119 patients. Pre-interventional FFR increased from 0.65 (0.15) to 0.94 (0.06) (p < 0.0001) after stent implantation. Eighteen MACE (15%) occurred during follow up including 15 (12.6%) target vessel revascularisations. Final FFR was significantly higher in patients without than in patients with an event (0.95 (0.05) v 0.88 (0.08), p = 0.001). In the multivariate logistic regression analysis, only final FFR < 0.95 (OR 6.22, 95% CI 1.79 to 21.62, p = 0.004) and reduced left ventricular function (OR 0.95, 95% CI 092 to 0.99, p = 0.021) remained as significant independent predictors for MACE. CONCLUSION: These results including multiple parameters underline that FFR after coronary stenting is a strong and independent predictor for subsequent cardiac events after six months' follow up.

Cost effectiveness of peginterferon alpha-2b plus ribavirin versus interferon alpha-2b plus ribavirin for initial treatment of chronic hepatitis C.

BACKGROUND: Peginterferon alpha-2b plus ribavirin therapy in previously untreated patients with chronic hepatitis C yields the highest sustained virological response rates of any treatment strategy but is expensive. AIMS: To estimate the cost effectiveness of treatment with peginterferon alpha-2b plus ribavirin compared with interferon alpha-2b plus ribavirin for initial treatment of patients with chronic hepatitis C. METHODS: Individual patient level data from a randomised clinical trial with peginterferon plus ribavirin were applied to a previously published and validated Markov model to project lifelong clinical outcomes. Quality of life and economic estimates were based on German patient data. We used a societal perspective and applied a 3% annual discount rate. RESULTS: Compared with no antiviral therapy, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 4.2 and 4.7 years, respectively. Compared with standard interferon alpha-2b plus ribavirin, peginterferon plus fixed or weight based dosing of ribavirin increased life expectancy by 0.5 and by 1.0 years with incremental cost effectiveness ratios of 11,800 euros and 6600 euros per quality adjusted life year (QALY), respectively. Subgroup analyses by genotype, viral load, sex, and histology showed that peginterferon plus weight based ribavirin remained cost effective compared with other well accepted medical treatments. CONCLUSIONS: Peginterferon alpha-2b plus ribavirin should reduce the incidence of liver complications, prolong life, improve quality of life, and be cost effective for the initial treatment of chronic hepatitis C.

Efficacy, routine effectiveness, and safety of horsechestnut seed extract in the treatment of chronic venous insufficiency. A meta-analysis of randomized controlled trials and large observational studies.

BACKGROUND: Safe and effective oral therapies for chronic venous insufficiency (CVI) would provide an important alternative to mechanical compression treatment. Several narrative reviews and one systematic review have summarized the efficacy of horse chestnut seed extract (HCSE), but to our knowledge no systematic review has included data from both randomized controlled trials (RCTs) and large-scale observational studies regarding outcomes as well as adverse events. METHODS: Using a systematic literature search, we identified 13 RCTs of CVI (1,051 patients) and 3 observational studies (10,725 patients) that met our inclusion criteria. Examined outcomes were leg volume, ankle and calf circumference, edema, pain, sensation of tension, swelling, leg fatigue/heaviness, calf cramps, and itching. Random and fixed effect models were used to pool outcomes and adverse events separately for RCTs and observational studies. RESULTS: Overall, the RCTs indicated that HCSE improved symptoms in patients with CVI. Compared to placebo, HCSE reduced leg volume by 46.4 ml (95% CI, 11.3-81.4 ml) and increased the likelihood of improvement in leg pain 4.1-fold (95% CI, 0.98-16.8). Similarly, improvement probabilities were increased 1.5-fold (95% CI, 1.2-1.9) for edema and 1.7-fold (95% CI, 0.01-3.0) for itching. There was insufficient evidence to demonstrate HCSE's effect on leg fatigue/heaviness or calf cramps. Observational studies showed significant effectiveness regarding pain, edema, and leg fatigue/heaviness. No severe adverse events were reported, and HCSE did not significantly increase mild adverse events. CONCLUSIONS: Based on meta-analyses of RCTs and observational studies, HCSE appears to be an effective and safe treatment for CVI. Further RCTs and carefully conducted large-scale observational studies are required to evaluate the long-term effectiveness and safety of HCSE in routine settings.