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Abstract Background This study's aim was to develop a first quantification of the frequency and costs of adverse drug events (ADEs) originating in ambulatory medical practice in Germany. Methods The frequencies and costs of ADEs were quantified for a base case, building on an existing cost-of-illness model for ADEs. The model originates from the U.S. health care system, its structure of treatment probabilities linked to ADEs was transferred to Germany. Sensitivity analyses based on values determined from a literature review were used to test the postulated results. Results For Germany, the base case postulated that about 2 million adults ingesting medications have will have an ADE in 2007. Health care costs related to ADEs in this base case totalled 816 million Euros, mean costs per case were 381 Euros. About 58% of costs resulted from hospitalisations, 11% from emergency department visits and 21% from long-term care. Base case estimates of frequency and costs of ADEs were lower than all estimates of the sensitivity analyses. Discussion The postulated frequency and costs of ADEs illustrate the possible size of the health problems and economic burden related to ADEs in Germany. The validity of the U.S. treatment structure used remains to be determined for Germany. The sensitivity analysis used assumptions from different studies and thus further quantified the information gap in Germany regarding ADEs. Conclusions This study found costs of ADEs in the ambulatory setting in Germany to be significant. Due to data scarcity, results are only a rough indication.

Abstract: Aims: To evaluate costs, effects and cost‐effectiveness of increased reach of specific smoking cessation interventions in Germany. Design: A Markov‐based state transition return on investment model (EQUIPTMOD) was used to evaluate current smoking cessation interventions as well as two prospective investment scenarios. A health‐care perspective (extended to include out‐of‐pocket payments) with life‐time horizon was considered. A probabilistic analysis was used to assess uncertainty concerning predicted estimates. Setting: Germany. Participants: Cohort of current smoking population (18+ years) in Germany. Interventions: Interventions included group‐based behavioural support, financial incentive programmes and varenicline. For prospective scenario 1 the reach of group‐based behavioral support, financial incentive programme and varenicline was increased by 1% of yearly quit attempts (= 57 915 quit attempts), while prospective scenario 2 represented a higher reach, mirroring the levels observed in England. Measurements: EQUIPTMOD considered reach, intervention cost, number of quitters, quality‐of‐life years (QALYs) gained, cost‐effectiveness and return on investment. Findings: The highest returns through reduction in smoking‐related health‐care costs were seen for the financial incentive programme (€2.71 per €1 invested), followed by that of group‐based behavioural support (€1.63 per €1 invested), compared with no interventions. Varenicline had lower returns (€1.02 per €1 invested) than the other two interventions. At the population level, prospective scenario 1 led to 15 034 QALYs gained and €27 million cost‐savings, compared with current investment. Intervention effects and reach contributed most to the uncertainty around the return‐on‐investment estimates. At a hypothetical willingness‐to‐pay threshold of only €5000, the probability of being cost‐effective is approximately 75% for prospective scenario 1. Conclusions: Increasing the reach of group‐based behavioural support, financial incentives and varenicline for smoking cessation by just 1% of current annual quit attempts provides a strategy to German policymakers that improves the population's health outcomes and that may be considered cost‐effective. [ABSTRACT FROM AUTHOR]

Objective: Metformin is used as a first-line oral treatment for type 2 diabetes (T2D). However, the underlying mechanism is not fully understood. Here, we aimed to comprehensively investigate the pleiotropic effects of metformin.Research Design and Methods: We analyzed both metabolomic and genomic data of the population-based KORA cohort. To evaluate the effect of metformin treatment on metabolite concentrations, we quantified 131 metabolites in fasting serum samples and used multivariable linear regression models in three independent cross-sectional studies (n = 151 patients with T2D treated with metformin [mt-T2D]). Additionally, we used linear mixed-effect models to study the longitudinal KORA samples (n = 912) and performed mediation analyses to investigate the effects of metformin intake on blood lipid profiles. We combined genotyping data with the identified metformin-associated metabolites in KORA individuals (n = 1,809) and explored the underlying pathways.Results: We found significantly lower (P < 5.0E-06) concentrations of three metabolites (acyl-alkyl phosphatidylcholines [PCs]) when comparing mt-T2D with four control groups who were not using glucose-lowering oral medication. These findings were controlled for conventional risk factors of T2D and replicated in two independent studies. Furthermore, we observed that the levels of these metabolites decreased significantly in patients after they started metformin treatment during 7 years' follow-up. The reduction of these metabolites was also associated with a lowered blood level of LDL cholesterol (LDL-C). Variations of these three metabolites were significantly associated with 17 genes (including FADS1 and FADS2) and controlled by AMPK, a metformin target.Conclusions: Our results indicate that metformin intake activates AMPK and consequently suppresses FADS, which leads to reduced levels of the three acyl-alkyl PCs and LDL-C. Our findings suggest potential beneficial effects of metformin in the prevention of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Vascular disease, including coronary heart disease (CAD), peripheral vascular disease and cerebrovascular disease, is the major cause of morbidity and death in diabetes. A recently introduced MRI technique was used to obtain an extensive assessment (excluding coronaries) of the vascular status in 65 diabetic patients. Methods: Long-standing ≥10 years) type 1 (n=20) or type 2 (n=45) diabetic patients (35 males, 63±13.1 years) were examined on a 1.5 Tesla or 3.0 Tesla whole body MRI. Cerebral arteries, abdominal aorta, and arteries of the upper and lower extremities (including pedal arteries) were imaged in one session (MR angiogram). Atherosclerotic lesions were quantified in each vessel (6 levels ranging from normal to occlusion) and the sum divided by the number of vessels evaluated resulted in an overall score, representing the patient's vascular status. The score's association with clinical and biochemical parameters was assessed with a generalized linear model (age and sex adjusted; SAS 9.1). Results: Age (p=0.0008) and male sex (p=0.029) were significantly associated with the score (r²=0.23). Adjusted for age and sex, the score was also associated with CAD status (r²=0.32; p=0.005), retinopathy (r²=0.31; p=0.007), serum creatinine (r²=0.34; p=0.006) and somewhat with diabetes duration (r²=0.26; p=0.07). BMI, blood pressure, smoking, type of diabetes, HbA1c, LDL-concentration and medications were not associated with the score. Conclusion: Our MRI based score evaluating vascular pathology (without coronaries) is significantly associated with CAD status, indicating that atherosclerosis has a similar etiology in coronary, cerebral and peripheral arteries in diabetes. Age, male sex, retinopathy, nephropathy (and perhaps duration of diabetes) are important predictors of an elevated score, indicating high atherosclerotic burden. BMI, blood pressure, HbA1c, LDL, and medications were not important predictors (probably because single on-treatment measurements were used). Whole-body MRI is a promising method for comprehensive atherosclerotic evaluation in diabetes. [ABSTRACT FROM AUTHOR]

Atherothrombosis can present as coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral arterial disease (PAD). It is unknown whether diabetic patients with CAD differ from those with CVD or PAD regarding clinical characteristics, biochemical parameters and medication. The REACH (REduction of Atherothrombosis for Continued Health) Registry contains data on over 68,000 patients with atherosclerosis or risk factors. The registry's primary goal is to evaluate vascular endpoints. In total, 5646 patients were recruited in Germany, 2390 (42%) of which are diabetic. Of these, 852 (36%) have only CAD, 286 (12%) have only CVD and 176 (7%) have only PAD. The others have either only risk factors (18%) or multiple manifestations (27%). The baseline data of diabetic patients (80% male, 68 ± 9 years, BMI 129 ± 5 kg/m²) with only CAD, or CVD, or PAD were evaluated (generalized linear model for continuous dependent variables, logistic regression for dependent variables with 2 classes; SAS). After correcting for age, sex and BMI, CAD patients receive (OR; 95% CI) statins (4.1; 2.9-5.9), beta-blockers (4.1; 4.9-10.5), diuretics (1.9; 1.3-2.6) and nitrates (8.7; 4.5-16.8) significantly more frequently and significantly less calcium-antagonists (0.73; 0.55-0.98). There was no difference concerning other antihypertensives, antidiabetics and platelet inhibitors. Medication differences resulted in significant ((*) p<0.05) differences between CAD compared to CVD and PAD regarding clinical and laboratory parameters (Table). Overall only few patients (CAD 9.5%, CVD 8.5%, PAD 0%) reach all treatment goals (BP-systolic ≤130mmHg, BP-diastolic ≤85mmHg, LDL≤100mg/dl, HDL≥40mg/dl, triglycerides ≤150mg/dl). These data indicate considerable differences in therapy between diabetics with CAD compared to those with CVD or PAD. Diabetics with CAD are treated more aggressively and therefore reach lower lipid values and lower blood pressure values. [ABSTRACT FROM AUTHOR]