Diabetes free life expectancy and years of life lost associated with type 2 diabetes: projected trends in Germany between 2015 and 2040

Background: Type 2 diabetes (T2D) causes substantial disease burden and is projected to affect an increasing number of people in coming decades. This study provides projected estimates of life years free of type 2 diabetes (T2D) and years of life lost (YLL) associated with T2D for Germany in the years 2015 and 2040. Methods: Based on an illness-death model and the associated mathematical relation between prevalence, incidence and mortality, we projected the prevalence of diagnosed T2D using currently available data on the incidence rate of diagnosed T2D and mortality rates of people with and without diagnosed T2D. Projection of prevalence was achieved by integration of a partial differential equation, which governs the illness-death model. These projected parameters were used as input values to calculate life years free of T2D and YLL associated with T2D for the German population aged 40 to 100 years in the years 2015 and 2040, while accounting for different assumptions on future trends in T2D incidence and mortality. Results: Assuming a constant incidence rate, women and men at age 40 years in 2015 will live approximately 38 years and 33 years free of T2D, respectively. Up to the year 2040, these numbers are projected to increase by 1.0 years and 1.3 years. Assuming a decrease in T2D-associated excess mortality of 2% per year, women and men aged 40 years with T2D in 2015 will be expected to lose 1.6 and 2.7 years of life, respectively, compared to a same aged person without T2D. In 2040, these numbers would reduce by approximately 0.9 years and 1.6 years. This translates to 10.8 million and 6.4 million YLL in the German population aged 40–100 years with prevalent T2D in 2015 and 2040, respectively. Conclusions: Given expected trends in mortality and no increase in T2D incidence, the burden due to premature mortality associated with T2D will decrease on the individual as well as on the population level. In addition, the expected lifetime without T2D is likely to increase. However, these trends strongly depend on future improvements of excess mortality associated with T2D and future incidence of T2D, which should motivate increased efforts of primary and tertiary prevention.Peer Reviewe

Meta-analysis of diagnostic accuracy studies with multiple thresholds – comparison of different approaches

Methods for standard meta-analysis of diagnostic test accuracy studies are well established and understood. For the more complex case in which studies report test accuracy across multiple thresholds, several approaches have recently been proposed. These are based on similar ideas, but make different assumptions. In this article, we apply four different approaches to data from a recent systematic review in the area of nephrology and compare the results. The four approaches use: a linear mixed effects model, a Bayesian multinomial random effects model, a time-to-event model and a nonparametric model, respectively. In the case study data, the accuracy of neutrophil gelatinase-associated lipocalin for the diagnosis of acute kidney injury was assessed in different scenarios, with sensitivity and specificity estimates available for three thresholds in each primary study. All approaches led to plausible and mostly similar summary results. However, we found considerable differences in results for some scenarios, for example, differences in the area under the receiver operating characteristic curve (AUC) of up to 0.13. The Bayesian approach tended to lead to the highest values of the AUC, and the nonparametric approach tended to produce the lowest values across the different scenarios. Though we recommend using these approaches, our findings motivate the need for a simulation study to explore optimal choice of method in various scenarios

Estimating the impact of tax policy interventions on the projected number and prevalence of adults with type 2 diabetes in Germany between 2020 and 2040

Introduction As a population-wide intervention, it has been proposed to raise taxes on unhealthy products to prevent diseases such as type 2 diabetes. In this study, we aimed to estimate the effect of tax policy interventions in 2020 on the projected prevalence and number of people with type 2 diabetes in the German adult population in 2040. Research design and methods We applied an illness-death model and the German Diabetes Risk Score (GDRS) to project the prevalence and number of adults with type 2 diabetes in Germany under a base case scenario and under a tax policy intervention scenario. For the base case scenario, we assumed constant age-specific incidence rates between 2020 and 2040. For the intervention scenario, we assumed a 50% price increase for sugar-sweetened beverages, tobacco and red meat products in the year 2020. Based on price elasticities, we estimated the impact on these risk factors alone and in combination, and calculated subsequent reductions in the age-specific and sex-specific GDRS. These reductions were used to determine reductions in the incidence rate and prevalence using a partial differential equation. Results Compared with the base case scenario, combined tax interventions in 2020 resulted in a 0.95 percentage point decrease in the prevalence of type 2 diabetes (16.2% vs 17.1%), which corresponds to 640 000 fewer prevalent cases of type 2 diabetes and a relative reduction by 6%. Conclusions Taxation of sugar-sweetened beverages, tobacco products and red meat by 50% modestly lowered the projected number and prevalence of adults with type 2 diabetes in Germany in 2040. Raising taxes on unhealthy products as a stand-alone measure may not be enough to attenuate the future rise of type 2 diabetes.Peer Reviewe

Establishing an MSU service in a medium-sized German urban area — clinical and economic considerations

Background and purpose: Mobile stroke units (MSU) have been demonstrated to improve prehospital stroke care in metropolitan and rural regions. Due to geographical, social and structural idiosyncrasies of the German city of Mannheim, concepts of established MSU services are not directly applicable to the Mannheim initiative. The aim of the present analysis was to identify major determinants that need to be considered when initially setting up a local MSU service. Methods: Local stroke statistics from 2015 to 2021 were analyzed and circadian distribution of strokes and local incidence rates were calculated. MSU patient numbers and total program costs were estimated for varying operating modes, daytime coverage models, staffing configurations which included several resource sharing models with the hospital. Additional case-number simulations for expanded catchment areas were performed. Results: Median time of symptom onset of ischemic stroke patients was 1:00 p.m. 54.3% of all stroke patients were admitted during a 10-h time window on weekdays. Assuming that MSU is able to reach 53% of stroke patients, the average expected number of ischemic stroke patients admitted to MSU would be 0.64 in a 10-h shift each day, which could potentially be increased by expanding the MSU catchment area. Total estimated MSU costs amounted to € 815,087 per annum. Teleneurological assessment reduced overall costs by 11.7%. Conclusion: This analysis provides a framework of determinants and considerations to be addressed during the design process of a novel MSU program in order to balance stroke care improvements with the sustainable use of scarce resources

Study protocol of the FIRE-8 (AIO-KRK/YMO-0519) trial: a prospective, randomized, open-label, multicenter phase II trial investigating the efficacy of trifluridine/tipiracil plus panitumumab versus trifluridine/tipiracil plus bevacizumab as first-line treatment in patients with metastatic colorectal cancer

Background: Initial systemic therapy for patients with metastatic colorectal cancer (mCRC) is usually based on two- or three-drug chemotherapy regimens with fluoropyrimidine (5-fluorouracil (5-FU) or capecitabine), oxaliplatin and/or irinotecan, combined with either anti-VEGF (bevacizumab) or, for RAS wild-type (WT) tumors, anti-EGFR antibodies (panitumumab or cetuximab). Recommendations for patients who are not eligible for intensive combination therapies are limited and include fluoropyrimidine plus bevacizumab or single agent anti-EGFR antibody treatment. The use of a monochemotherapy concept of trifluridine/ tipiracil in combination with monoclonal antibodies is not approved for first-line therapy, yet. Results from the phase II TASCO trial evaluating trifluridine/tipiracil plus bevacicumab in first-line treatment of mCRC patients and from the phase I/II APOLLON trial investigating trifluridine/tipiracil plus panitumumab in pre-treated mCRC patients suggest favourable activity and tolerability of these new therapeutic approaches. Methods: FIRE-8 (NCT05007132) is a prospective, randomized, open-label, multicenter phase II study which aims to evaluate the efficacy of first-line treatment with trifluridine/tipiracil (35 mg/m(2) body surface area (BSA), orally twice daily on days 1-5 and 8-12, q28 days) plus either the anti-EGFR antibody panitumumab (6 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm A] or (as control arm) the anti-VEGF antibody bevacizumab (5 mg/kg body weight, intravenously on day 1 and 15, q28 days) [arm B] in RAS WT mCRC patients. The primary objective is to demonstrate an improved objective response rate (ORR) according to RECIST 1.1 from 30% (control arm) to 55% with panitumumab. With a power of 80% and a two-sided significance level of 0.05, 138 evaluable patients are needed. Given an estimated drop-out rate of 10%, 153 patients will be enrolled. Discussion: To the best of our knowledge, this is the first phase II trial to evaluate the efficacy of trifluridine/tipiracil plus panitumumab in first-line treatment of RAS WT mCRC patients. The administration of anti-EGFR antibodies rather than anti-VEGF antibodies in combination with trifluridine/tipiracil may result in an increased initial efficacy

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]