Health economic benefits through the use of diagnostic support systems and expert knowledge.

BACKGROUND: Rare diseases are difficult to diagnose. Due to their rarity, heterogeneity, and variability, rare diseases often result not only in extensive diagnostic tests and imaging studies, but also in unnecessary repetitions of examinations, which places a greater overall burden on the healthcare system. Diagnostic decision support systems (DDSS) optimized by rare disease experts and used early by primary care physicians and specialists are able to significantly shorten diagnostic processes. The objective of this study was to evaluate reductions in diagnostic costs incurred in rare disease cases brought about by rapid referral to an expert and diagnostic decision support systems. METHODS: Retrospectively, diagnostic costs from disease onset to diagnosis were analyzed in 78 patient cases from the outpatient clinic for rare inflammatory systemic diseases at Hannover Medical School. From the onset of the first symptoms, all diagnostic measures related to the disease were taken from the patient files and documented for each day. The basis for the health economic calculations was the Einheitlicher Bewertungsmaßstab (EBM) used in Germany for statutory health insurance, which assigns a fixed flat rate to the various medical services. For 76 cases we also calculated the cost savings that would have been achieved by the diagnosis support system Ada DX applied by an expert. RESULTS: The expert was able to achieve significant savings for patients with long courses of disease. On average, the expert needed only 27 % of the total costs incurred in the individual treatment odysseys to make the correct diagnosis. The expert also needed significantly less time and avoided unnecessary examination repetitions. If a DDSS had been applied early in the 76 cases studied, only 51-68 % of the total costs would have incurred and the diagnosis would have been made earlier. Earlier diagnosis would have significantly reduced costs. CONCLUSION: The study showed that significant savings in the diagnostic process of rare diseases can be achieved through rapid referral to an expert and the use of DDSS. Faster diagnosis not only achieves savings, but also enables the right therapy and thus an increase in the quality of life for patients.

Impact of wound duration on diabetic foot ulcer healing: evaluation of a new sucrose octasulfate wound dressing.

OBJECTIVE: A common and frequent complication of diabetes is diabetic foot ulcers (DFU), which can have high treatment costs and severe adverse events. This study aims to evaluate the effects of wound duration on wound healing and the impact on costs, including treatment with a new sucrose octasulfate dressing compared with a control dressing. METHOD: Based on the Explorer study (a two-armed randomised double-blind clinical trial), a cost-effectiveness analysis compared four different patient groups distinguished by their wound duration and additionally two DFU treatment options: a sucrose octasulfate dressing and a neutral dressing (as control). Clinical outcomes and total direct costs of wound dressings were evaluated over 20 weeks from the perspective of the Social Health Insurance in Germany. Simulation of long-term outcomes and costs were demonstrated by a five cycle Markov model. RESULTS: The results show total wound healing rates between 71% and 14.8%, and direct treatment costs for DFU in the range of €2482-3278 (sucrose octasulfate dressing) and €2768-3194 (control dressing). Patients with a wound duration of ≤2 months revealed the highest wound healing rates for both the sucrose octasulfate dressing and control dressing (71% and 41%, respectively) and had the lowest direct treatment costs of €2482 and €2768, respectively. The 100-week Markov model amplified the results. Patients with ≤2 months' wound duration achieved wound healing rates of 98% and 88%, respectively and costs of €3450 and €6054, respectively (CE=€3520, €6864). Sensitivity analysis revealed that the dressing changes per week were the most significant uncertainty factor. CONCLUSION: Based on the findings of this study, early treatment of DFU with a sucrose octasulfate dressing is recommended from a health economic view due to lower treatment costs, greater cost-effectiveness and higher wound healing rates.

Cost-effectiveness of TLC-sucrose octasulfate versus control dressings in the treatment of diabetic foot ulcers.

OBJECTIVE: Diabetes is one of the most widespread diseases in Germany. Common complications are diabetic foot ulcers (DFU), which are associated with a cost-intensive treatment and serious adverse events, such as infections, amputations. This cost-effectiveness analysis compares two treatment options for patients with DFU: a TLC-NOSF dressing versus a neutral dressing, assessed through a European double-blind randomised controlled trial (RCT), Explorer. METHODS: The evaluation of the clinical outcomes was associated to direct costs (costs for dressings, nursing time, hospitalisation etc.) of both dressings, from the perspective of the statutory health insurance in Germany. Due to the long mean healing time of a DFU, the observation period was extended from 20 to 100 weeks in a Markov model. RESULTS: After 20 weeks, and with complete closure as a primary endpoint, the model revealed direct treatment costs for DFU of €2,864.21 when treated with a TLC-NOSF dressing compared with €2,958.69 with the neutral control dressing (cost-effectiveness: €6,017.25 versus €9,928.49). In the Markov model (100 weeks) the costs for the TLC-NOSF dressing were €5,882.87 compared with €8,449.39 with the neutral dressing (cost-effectiveness: €6,277.58 versus €10,375.56). The robustness of results was underlined by several sensitivity analyses for varying assumptions. The frequency of weekly dressing changes had the most significant influence in terms of parameter uncertainty. CONCLUSION: Overall, the treatment of DFU with a TLC-NOSF dressing is supported from a health economic perspective, because both the treatment costs and the cost-effectiveness were superior compared with the neutral wound dressing.

Hospitalization rates and resource utilization of schizophrenic patients switched from oral antipsychotics to aripiprazole-depot in Germany.

OBJECTIVE: Examine cost-driving factors of schizophrenia in Germany for patients prior- and post-switch from an oral antipsychotic therapy to aripiprazole-depot and perform a budget impact analysis (BIA) referring to the context of German health care. METHODS: A single-armed, retrospective, non-interventional pre-post comparison study with 132 patients to compare the total psychiatric hospitalization rates and the associated costs of both, the treatment with oral antipsychotics and aripiprazole-depot. The BIA was performed to compare both treatment periods with respect to health-related costs. A subsequent univariate sensitivity analysis examined the robustness of the results. RESULTS: After switching the treatment to aripiprazole-depot, the total psychiatric hospitalization rates for the 6-month treatment period were significantly (p < 0.001) lower (14%) compared to the hospitalization rates when treated with oral antipsychotics (55.1%). 18.2% of the patients reported to be employed, with 29.2% having work incapacities. The mean number of schizophrenia episodes was 2.58 episodes per patient during the oral-antipsychotic treatment compared to 0.41 episodes per patient during the aripiprazole-depot phase (p < 0.001). The treatment with aripiprazole-depot also significantly reduced the mean number of hospitalizations per patient (0.63 to 0.16, p < 0.001) and the mean number of hospitalized days (27.39 to 5.56, p < 0.001) compared to the oral antipsychotic treatment. Additionally a significant reduction of the mean stay in day-clinics and psychiatric institute ambulances (PIAs) was observed (46.13 days to 7.29 days, p < 0.01). Treatment of a patient suffering from schizophrenia with oral antipsychotics produced costs of 9935.38€ (direct costs: 9498.36 €), while aripiprazole-depot generated costs of 4557.56€ (direct costs: 4449.83 €) per patient for a one-year observation period. This resulted in total costs of 6,517,606,265.43€ for the oral antipsychotic treatment and 2,989,756,603.05€ for aripiprazole-depot treatment from the perspective of the German health care system. The results remained robust during sensitivity analysis, with aripiprazole-depot being the more cost-effective strategy. CONCLUSIONS: The results suggest that aripiprazole-depot treatment for schizophrenia patients has major potential in terms of cost savings for the German statutory health insurance.

Elevating the use of sugar-free chewing gum in Germany: cost saving and caries prevention.

OBJECTIVE: To analyse the lifetime monetary and health related effects of the consumption of sugar-free chewing gum. MATERIAL AND METHODS: Using a Markov model we assumed that the German consumption of sugar-free chewing gum (111 gums/year) could be elevated to the level of Finland (202 gums/year). The calculation was based on a model patient representing the development of oral health from the age of 12 to 74 years and clinical data on the effectiveness of chewing sugar-free gum. Lifetime and yearly costs for the 'Finland-scenario' were determined and compared with the actual German expenses of the statutory health insurance companies for dental health. RESULTS: The actual total lifetime expenditures of the statutory health insurance companies are 17,199.96€ per capita and would be 12,188.94€ in the scenario with elevated consumption of sugar-free chewing gum in Germany. Thus, 5011.02€ per capita could be saved in a lifetime and 80.82€ per year. CONCLUSIONS: On a national scale, the elevation of the consumption of sugar-free chewing gum in Germany to the level of Finland would lead to a considerable benefit for cost saving and oral health for the statutory health insurance companies.

A global approach to assess the economic benefits of increased consumption of sugar-free chewing gum.

PURPOSE: To analyze the influence of increasing the average consumption of sugar-free gum (SFG) in 25 industrialized countries on dental expenditures due to caries by the national health care systems. It was assumed that large cost savings were possible, because the regular consumption of SFG significantly reduces the relative risk of caries and therefore, improves dental health, which reduces expenditures on dental treatments. METHODS: A budget impact analysis (BIA) was performed to model the decrease in the relative risk of caries and the subsequent cost savings for dental care. Annual consumption of SFG, dental expenditures due to caries, chewing frequencies by age groups and the relative risk reduction for caries due to the consumption of SFG were identified and used as model parameters. Three different scenarios for the increase in the number of SFG were calculated. Besides overall results for all countries together, analyses were conducted for countries grouped by regions and the Human Development Index (HDI). RESULTS: For the entity of all 25 analyzed countries together, possible annual cost savings range from US$805.77 M in the scenario with the lowest increase of SFG consumption up to US$18,248 billion in the scenario with the biggest increase of SFG consumption. Europe and the USA show potential cost savings of US$1,061 billion and US$2,071 billion per year, respectively, if all chewers increase their consumption of SFG by 1 piece per day. The analysis showed the potential cost savings in dental expenditures due to caries that can be achieved by only slightly increasing the consumption of SFG. The regular consumption of SFG cannot replace good dental hygiene like tooth brushing, but can have a significant impact on dental health, which can lead to increased cost savings for health care systems worldwide. CLINICAL SIGNIFICANCE: Based on the fact that a regular consumption of sugar-free chewing gum has the beneficial effect of reducing caries prevalence, an increased consumption may not only lead to improved dental health but significant cost savings in expenditures for dental treatment worldwide.

[Improvement of Stress Resistance and Quality of Life of Adults with Nervous Restlessness after Treatment with a Passion Flower Dry Extract].

BACKGROUND: The passion flower dried ethanolic extract investigated in this non-interventional study has well-documented calmative effects and good tolerability. We investigated the effects of this extract on the stress resistance (resilience) and quality of life (QoL) of patients suffering from nervous restlessness. The addiction potential of the drug and the course of symptoms were also evaluated. METHODS: Adult patients aged ≤ 95 years with the diagnosis 'nervous restlessness' were treated for 12 weeks with a dried ethanolic extract of passion flower (Passiflora incarnata L.). Standardized questionnaires were used to evaluate the resilience (RS-13), QoL (EQ-5D including EQ-VAS), and the addiction potential (BDEPQ). RESULTS: After 12 weeks of treatment, significant (p < 0.001) improvements were measured in the patients' resilience (RS-13: from 52.1 to 67.7 points) and QoL (EQ-VAS: from 47.9 to 75.0 points). Also, the mean BDEPQ score was significantly (p < 0.001) reduced (from 23.0 to 19.3 points). The mean values of all accompanying symptoms (inner restlessness, sleep disturbance, exhaustion, fear, lack of concentration, transpiration, nausea, trembling, and palpitation) improved significantly (p < 0.001). Tolerability of treatment was rated as 'very good' or 'good' by the majority of the patients. Three cases of mild adverse events (tiredness) were reported. CONCLUSION: The passion flower extract investigated in the present study appears to be effective in improving resilience and QoL in patients suffering from nervous restlessness and is well tolerated.

[Medical care and costs in the last year of life - propensity score matching of AAPV and SAPV insurants]. / Medizinische Versorgung und Kosten im letzten Lebensjahr.

INTRODUCTION: Patients with life limiting diseases need special medical treatments at the end of life. In Germany, since 2007 there is specialized outpatient palliative care (SAPV) available for patients in need of special treatments additional to regular outpatient palliative care (AAPV). Distribution of specialized palliative care is not homogenous in german regions and there is no evidence about medical gain and total costs yet. METHODS: Deceased patients from both groups are compared by propensity score matching with regard to their medical biographies of their last year of life. This retrospective study uses data of the health insurance company DAK. The data set contains information about items of medical care including their particular costs. RESULTS: Results show significant higher costs for patients in specialized care settings with exception of nursing costs. The most striking difference was found for drug expenditures which were twice as much for patients in specialized care than for patients treated with regular outpatient palliative care. CONCLUSION: The specialty of care is represented by the average costs of specialized outpatient palliative care in patients last year of life. A proportion of 75% of the costs for specialized outpatient palliative care follow from temporary inpatient care and drug expenditures. Further investigations should measure to what extend higher costs are resulting from additional benefits of care and how they could be interpreted in terms of cost efficiency.

Quality of life and costs of spasticity treatment in German stroke patients.

OBJECTIVE: To gather data about the medical and non-medical health service in patients suffering from post-stroke spasticity of the upper limb and evaluate treatment effectiveness and tolerability as well as costs over the treatment period of one year. METHODS: Prospective, non-interventional, multicenter, parallel-group study comparing effectivenessand costs of incobotulinumtoxinA (INCO) treatment (n = 118) to conventional (CON) antispastic therapy (n = 110) for upper limb spasticity after stroke in 47 clinical practices across Germany over a 1-year treatment period. IncobotulinumtoxinA was applied according to the individual treatment algorithms of each participating site and additional antispastic treatments were allowed. Primary efficacy objective was the reduction of the muscle tone measured by Ashworth scale. Responder analyses and logistic regressions were performed. Quality of life, measured by SF-12 questionnaire and functional disability were assessed. Besides calculating treatment costs, a cost-utility analysis was performed. RESULTS: Responder rates of all muscle groups of the upper extremities were significantly higher in the treatment group (62.9-86.2 % vs. 15.5-26.9 %, p < 0.01). Total health service costs were twice as high in the INCO group, however cost-utility ratios were consistently superior compared to the control group. Lowest incremental costs were documented to improve the "physical health" dimension in quality of life. CONCLUSION: Higher responder rates, higher increases in quality of life and superior cost-utility ratios in the BoNT/A-treatment group underline guideline recommendations for botulinum toxin A treatment in focal or segmental spasticity. Results may partially be influenced by different patient demographics or disease severity at study entry.

Cost-effectiveness of treating vascular leg ulcers with UrgoStart(®) and UrgoCell(®) Contact.

Although chronic wounds have a high socio-economic impact, data on comparative effectiveness of treatments are rare. UrgoStart(®) is a hydroactive dressing containing a nano-oligosaccharide factor (NOSF). This study aimed at evaluating the cost-effectiveness of this NOSF-containing wound dressing in vascular leg ulcers compared with a similar neutral foam dressing (UrgoCell(®) Contact) without NOSF. Cost-effectiveness analysis from the perspective of the German statutory health care system was performed using a decision tree model for a period of 8 weeks. Cost and outcome data were derived from the clinical study 'Challenge' suggesting a response rate (≥40% wound size reduction) of UrgoStart(®) of 65·6% versus 39·4% for the comparator. In the treatment model, effect-adjusted costs of €849·86 were generated after 8 weeks for treatment with UrgoStart(®) versus €1335·51 for the comparator resulting in an effect-adjusted cost advantage of €485·64 for UrgoStart(®) . In linear sensitivity analyses, the outcomes were stable for varying assumptions on prices and response rates. In an 8-week period of treatment for vascular leg ulcers, UrgoStart(®) shows superior cost-effectiveness when compared with the similar neutral foam dressing without any active component (NOSF). As demonstrated within a randomised, double-blind clinical trial, UrgoStart(®) is also more effective in wound area reduction than the neutral foam dressing. Wound healing was not addressed in this clinical trial. Follow-up data of 12 months to allow for reulceration assessment were not generated.

Long-term efficacy and safety of incobotulinumtoxinA and conventional treatment of poststroke arm spasticity: a prospective, non-interventional, open-label, parallel-group study.

OBJECTIVE: To compare the efficacy and safety of incobotulinumtoxinA with conventional antispastic therapy for poststroke arm spasticity in routine clinical practice over a 1-year period. DESIGN: Prospective, non-interventional, open-label, parallel-group study. SETTING: 47 centres in Germany. PARTICIPANTS: Patients with poststroke arm spasticity; 108 receiving incobotulinumtoxinA, 110 conventional therapy. INTERVENTION: Conventional antispastic treatment including oral antispastic medications, physiotherapy and occupational therapy or 3-monthly incobotulinumtoxinA injections plus conventional therapy if required. MAIN OUTCOME MEASURES: The main outcome measure was changes in muscle tone (Ashworth Scale) over the 1-year treatment period. Changes in functional disability (Disability Assessment Scale) and quality of life (Short-Form-12 Health Survey) were additionally assessed. Ratings for therapy outcome (Goal Attainment Scale), and efficacy and tolerability of treatment (Global Clinical Impression Scale) were also obtained. RESULTS: Muscle tone improved for all spasticity patterns with the Ashworth Scale responder rates between 63% and 86% (incobotulinumtoxinA) and 16-27% (conventional therapy). Median improvement in functional disability was -1.0 (incobotulinumtoxinA) and 0.0 (conventional measures) for all domains. Treatment goals were attained by 93% of incobotulinumtoxinA patients and 30% of patients under conventional therapy. Most physicians (93%) and patients (90%) rated efficacy as good or very good under incobotulinumtoxinA; the proportions were much lower under conventional therapy (36% and 37%). Tolerability under incobotulinumtoxinA was considered good or very good by 99% of physicians and patients (76% and 66%, respectively, under conventional therapy). Quality of life under incobotulinumtoxinA improved by 8.0 (physical score) and 10.8 (mental score) and by 0.8 and 5.7, respectively, under conventional therapy. CONCLUSIONS: IncobotulinumtoxinA combined with rehabilitation and oral medication produces a much more robust improvement in all aspects of arm spasticity than conventional antispastic treatment. Effects are stable over a period of 1 year, whereas adverse effects are negligible. IncobotulinumtoxinA should be considered the treatment of choice for poststroke arm spasticity.

Pancreatic enzyme replacement therapy in patients with exocrine pancreatic insufficiency due to chronic pancreatitis: a 1-year disease management study on symptom control and quality of life.

OBJECTIVE: Exocrine pancreatic insufficiency (EPI) is frequent in patients with chronic pancreatitis (CP). This 1-year, prospective, multicenter, observational, disease management study aimed to assess symptom improvement and quality of life in patients with CP with EPI who were receiving pancreatic enzyme replacement. METHODS: Patients with CP and chronic EPI were either assigned to cohort 1 that consisted of patients already taking pancreatin (Kreon; Abbott Arzneimittel GmbH, Hannover, Germany) or cohort 2 that consisted of patients with newly diagnosed EPI without prior pancreatic enzyme treatment. Symptoms were documented, and quality of life was assessed using the gastrointestinal quality of life index (GIQLI) at baseline, 6 months, and 1 year. RESULTS: A total of 294 patients were evaluated (cohort 1, n = 206; cohort 2, n = 88). The proportion of patients experiencing gastrointestinal symptoms and recurrent pain after 1 year was significantly reduced in both cohorts (P < 0.001). The alleviation of symptoms was reflected in GIQLI score improvements at 1 year in both cohorts (P < 0.001), independent of CP severity and etiology. Improvements in GIQLI score were more pronounced in cohort 2 (P < 0.001). CONCLUSIONS: Pancreatin demonstrated symptom relief and improvement in quality of life in patients with CP-related EPI in this disease management study.

Cost-effectiveness analysis, prevention of atopic dermatitis by oral application of bacterial lysate in newborns/small children.

OBJECTIVES: The aim of this analysis was to determine the cost-effectiveness compared to placebo of prophylactic treatment with sterile bacterial lysate (Escherichia coli and Enterococcus faecalis) (verum) of newborns/small children with heredity for atopy [atopic dermatitis (AD)]. Infants were followed from the age of 5 weeks until 3 years of age. During this time, the number of children with AD who were treated with verum or placebo was observed at eight visits. Cost-effectiveness analyses were performed at different time points. METHODS: A randomized, double-blind placebo-controlled clinical trial performed in Germany included 606 newborns. After randomization, n = 303 patients were classified in the placebo group and n = 303 in the verum group. A total of 119 participants left the study, so data from n = 250 patients of the placebo group and n = 237 patients of the verum group were available for analysis. At the beginning of the study, newborns were treated prophylactically with bacterial lysate or placebo for 26 weeks. After this, children were observed until the age of 3 years. A systematic literature research was done to evaluate treatment costs of atopic eczema in newborn/small children. Finally, 17 publications were included and checked for searched treatment costs of AD. A study was then initiated to evaluate the direct costs to statutory health insurance. Based on the described clinical trial, a decision tree model was developed. Using the evaluated direct costs and prevalence according to the clinical trial, the developed model can be used in cost-effectiveness analyses. RESULTS: The focus of the analyses was on the subgroup "single heredity for atopy" in clinical trials. Cost-effectiveness analysis showed an advantage for bacterial lysate after 3 years. To further support this result a model extension was executed; the model was expanded from 3 to 6 years. Cost-effectiveness of bacterial lysate was also proven after 6 years. CONCLUSION: Prophylactic treatment with bacterial lysate of infants with single heredity for atopy for 26 weeks in the 1st year of life is cost-effective at the age of 3 and 6 years, i.e. prophylactic use of bacterial lysate generated lower costs by leading to lower prevalence compared to placebo.

Direct costs of Alzheimer's disease in Germany.

OBJECTIVES: The aim of this analysis was to determine the direct costs for patients with Alzheimer's disease (AD) based on data supplied by a large German statutory health insurance (BARMER). Focus of the present evaluation is the exposure of total direct costs, survival rates and the types of care distribution of patients with AD. METHODS: The analysis was based on anonymised data of patients with Alzheimer's disease who were insured by a large German statutory health insurance (Barmer Ersatzkasse-BEK) in 2005 over 12 months (n = 35.684). The study population was classified into three treatment groups: patients who received memantine and no other antidementia drugs, psychotropic drugs or sedatives/hypnotics (memantine group); patients who neither received memantine nor other antidementia drugs but psychotropic drugs and/or sedatives/hypnotics (PHS group); and patients who received no antidementia drugs and no psychotropic drugs or sedatives/hypnotics (no AT group). A Markov model was designed to assess the costs of each treatment group depending on the type of care over a 5-year period. RESULTS: The results obtained for the PHS group were the following: after 5 years, 25.1% were in inpatient health care, 1.1% in partial inpatient care, 5.4% in outpatient care, and 64.5% of patients died. Only 3.9% did not require care. On average, direct costs to the amount of 7.948 € incurred per patient and year and 13.099 € per surviving patient. In the group without pharmacotherapy, 20.6% were in inpatient care, 0.3% in partial inpatient care, 12.8% in outpatient care, and 52.5% of the patients died. For 13.8% of the patients, care was not necessary. The annual costs amounted to 6.760 € per patient and 9.926 € per surviving patient. The results obtained for the memantine group were more beneficial: annual costs per patient amounted to 6.100 € and to 8.376 € per surviving patient. CONCLUSIONS: The results demonstrate that non-antidementive therapy for Alzheimer's disease causes higher costs especially for care. The memantine group proved to be superior compared to PHS group and no AT group, despite higher costs in the specific drug category.

[Cost of illness in Alzheimer's disease]. / Krankheitskosten bei Alzheimer-Demenz.

PURPOSE: The aim of this analysis was to generate cost data of provider services, drug acquisition, hospitalization, nursing care services, and adjuvants for patients with Alzheimer's disease, as well as to describe the distribution and development of care levels. MATERIAL AND METHODS: The analysis is based on anonymized data of patients with Alzheimer's disease who were insured by a large German statutory health insurance (Barmer Krankenkasse [BARMER]) in 2005 (n = 48,322). The study population was classified into three treatment groups: patients, who received memantine and no other antidementives, psychotropic drugs or hypnotics/sedatives (memantine group); patients who neither received memantine nor other antidementives, but psychotropic drugs and hypnotics/ sedatives (PHS group); and patients who received no antidementives or symptomatic therapy at all ("no dementia-specific AM"). Costs were fully assessed for patients in each treatment group and correlated with the care level. RESULTS: In the memantine group, fewer patients needed care than in the other two groups. Total costs per patient averaged 7,028 Euros in the memantine group, 13,549 Euros in the PHS group, and 8,817 Euros in the group with no specific medication. Higher costs in the PHS group and in the group without drug treatment were mainly caused by a considerably higher rate of patients in need of care, of which nursing care made up the highest proportion. Fewer costs for medical treatment could not compensate the additional expenditures for nursing care. Patients in the PHS group had the highest average costs in all cost categories except for specific drug cost. CONCLUSION: The results demonstrate that non-antidementive therapy for Alzheimer's disease causes higher costs especially in nursing care. The memantine group proved superior even though it had the highest costs in the specific drug category.

New-onset diabetes and antihypertensive treatment.

INTRODUCTION: Chronic diseases substantially contribute to the continuous increase in health care expenditures, including type-2 diabetes mellitus as one of the most expensive chronic diseases. Arterial hypertension presents a risk factor for the development of type-2 diabetes mellitus. Numerous analyses have demonstrated that antihypertensive therapies promote the development of type-2-diabetes mellitus. Studies indicate, that the application of angiotensin converting enzyme (ACE) inhibitors and angiotensin-receptor-blockers (ARB) lead to less new-onset diabetes compared to beta-blockers, diuretics and placebo. Given that beta-blockers and diuretics impair the glucose metabolism, the metabolic effects of different antihypertensive drugs should be regarded; otherwise not only the disease itself, but also antihypertensive therapies may promote the development of new-onset diabetes. Even though, the cost of ACE inhibitors and ARB are higher, the use in patients with metabolic disorders could be cost-effective in the long-term if new-onset diabetes is avoided. OBJECTIVES: To evaluate which class of antihypertensive agents promote the development or the manifestation of type-2 diabetes mellitus. How high is the incidence of new-onset diabetes during antihypertensive therapy and how is treatment-induced type-2 diabetes mellitus evaluated clinically? Which agents are therefore cost-effective in the long term? Which ethical, social or legal aspects should be regarded? METHODS: A systematic literature review was conducted including clinical trials with at least ten participants which reported new-onset diabetes in the course of antihypertensive treatment. The trials had to be published after 1966 (after 2003 for economic publications) in English or German. RESULTS: A total of 34 clinical publications meet the inclusion criteria. Of these, eight publications focus on the development of diabetes mellitus under treatment with diuretic and/or beta-blockers, six publications focused on ACE inhibitors alone or in combination with calcium-channel-blockers, ten publications on ARB and/or ACE inhibitors with respect to their effects on new-onset diabetes or their preventive aspects. Furthermore, five publications investigate the role of calcium-channel-antagonists in the development of diabetes, and five publications indicate the development of new-onset diabetes with different antihypertensive agents amongst each other or in comparison to no antihypertensive treatment. The clinical trials show a significant difference in the development of new-onset diabetes. Therapies with diuretics and/or beta-blockers result in a higher incidence of new-onset diabetes. ARB as well as ACE inhibitors have a preventive effect and calcium-channel-blockers show a neutral position regarding the development of new-onset diabetes. Two publications report on economic results. The first one evaluates the cost-effectiveness of ARB alone or in combination with calcium-channel-blockers in comparison to diuretics alone or in combination with beta-blockers. The second publication compares economic outcomes of calcium-channel-blockers and beta-blockers considering the development of new-onset diabetes. Treatment with the ARB candesartan lead to savings in total costs of 549 US-Dollar per patient and in incremental costs of 30,000 US-Dollar per diabetes mellitus avoided. In the second publication, costs to the amount of 18,965 Euro in Great Britain and 13,210 Euro in Sweden are quoted for an avoided event. The treatment with calcium-channel-blockers compared to beta-blockers is proven to be more cost-effective. No publications were identified regarding ethical, social and legal aspects. DISCUSSION: The available meta-analyses allow for a high clinical evidence level. A few studies vary in terms of diabetes definition and study duration. In most of the trials, the incidence of new-onset diabetes is not an endpoint. The evaluation of treatment-induced diabetes mellitus cannot be conducted, due to the lack of sufficient results in the identified literature. The two economic studies do not address all the objectives sufficiently. Ethical, social and legal aspects are discussed but not analysed systematically. CONCLUSION: Based on these studies, sufficient evidence to confirm the presumption that diuretics and/or beta-blockers promote the development of new-onset diabetes compared to other antihypertensive agents, especially in patients who are predisposed, is presented with this report. Trials reflecting the clinical relevance of treatment-induced diabetes mellitus compared to existing diabetes mellitus regarding cardiovascular outcomes are required. Also health economic evaluations considering the development of new-onset diabetes should be conducted for the different classes of antihypertensive agents.