Sex differences in skeletal muscle-aging trajectory: same processes, but with a different ranking.

Sex differences in muscle aging are poorly understood, but could be crucial for the optimization of sarcopenia-related interventions. To gain insight into potential sex differences in muscle aging, we recruited young (23 ± 2 years, 13 males and 13 females) and old (80 ± 3.5 years, 28 males and 26 females) participants. Males and females in both groups were highly matched, and vastus lateralis muscle parameters of old versus young participants were compared for each sex separately, focusing on gene expression. The overall gene expression profiles separated the sexes, but similar gene expression patterns separated old from young participants in males and females. Genes were indeed regulated in the same direction in both sexes during aging; however, the magnitude of differential expression was sex specific. In males, oxidative phosphorylation was the top-ranked differentially expressed process, and in females, this was cell growth mediated by AKT signaling. Findings from RNA-seq data were studied in greater detail using alternative approaches. In addition, we confirmed our data using publicly available data from three independent human studies. In conclusion, top-ranked pathways differ between males and females, but were present and altered in the same direction in both sexes. We conclude that the same processes are associated with skeletal muscle aging in males and females, but the differential expression of those processes in old vs. young participants is sex specific.

Survival of Escherichia coli O157:H7 and Salmonella on Bruised and Unbruised Tomatoes from Three Ripeness Stages at Two Temperatures.

Tomatoes are one of the major fresh produce commodities consumed in the United States. Harvesting tomato fruit at a later stage of development can enhance consumer acceptance but can also increase damage due to bruising. Bruising can affect the quality of whole tomatoes by causing an unacceptable appearance and accelerating decay. Bruising may also facilitate bacterial attachment to the fruit surface and support growth of pathogens. This study evaluated the survival and/or proliferation of Escherichia coli O157:H7 and Salmonella on the surface of artificially bruised and unbruised tomatoes at three ripeness stages (breaker, pink, and red) and two storage temperatures (10 and 20°C). A total of 1,440 tomatoes, 720 for each organism, were analyzed. Both E. coli O157:H7 and Salmonella counts declined significantly ( P < 0.05) on the bruised and unbruised tomatoes over the 7-day storage period, by approximately 2.5 and 2.0 log, respectively. E. coli O157:H7 was not detected on pink tomatoes on day 7, whereas Salmonella persisted on the tomato surfaces throughout the 7-day study at all ripeness stages. Bruising had no significant effect ( P > 0.05) on the survival of E. coli O157:H7 (CFU per tomato) compared with the unbruised tomatoes, in most cases. Tomatoes from the red ripeness stage showed a significant effect ( P < 0.05) of bruising on Salmonella survival at both 10 and 20°C. Similar to the colony count results, the frequency (presence or absence) of inoculated tomatoes with detectable levels of inoculated bacteria decreased significantly ( P < 0.05) over time. At the lower temperature, E. coli O157:H7 was recovered from significantly higher ( P < 0.05) numbers of breaker and pink tomatoes, whereas there was no effect of temperature on the overall survival of E. coli O157:H7 on red tomatoes. Results from this study are essential for understanding the effects of bruising on produce safety and for producers and packers to develop mitigation strategies to control pathogenic and spoilage organisms.

Loss of cAMP/CRP regulation confers extreme high hydrostatic pressure resistance in Escherichia coli O157:H7.

Application of high hydrostatic pressure (HHP) constitutes a valuable non-thermal pasteurization process in modern food conservation. Triggered by our interest in the rapid adaptive evolution towards HHP resistance in the food-borne pathogen E. coli O157:H7 (strain ATCC 43888) that was demonstrated earlier, we used genetic screening to identify specific loci in which a loss-of-function mutation would be sufficient to markedly increase HHP survival. As such, individual loss of RssB (anti RpoS-factor), CRP (catabolite response protein) and CyaA (adenylate cyclase) were each found to confer significant HHP resistance in the 300MPa range (i.e. >1,000-fold), and this phenotype invariably coincided with increased resistance against heat as well. In contrast to loss of RssB, however, loss of CRP or CyaA also conferred significantly increased resistance to 600MPa (i.e. >10,000-fold), suggesting cAMP/CRP homeostasis to affect extreme HHP resistance independently of increased RpoS activity. Surprisingly, none of the rapidly emerging HHP-resistant mutants of ATCC 43888 that were isolated previously did incur any mutations in rssB, crp or cyaA, indicating that a number of other loci can guide the rapid emergence of HHP resistance in E. coli O157:H7 as well. The inability of spontaneous rssB, crp or cyaA mutants to emerge during selective enrichment under HHP selection likely stems from their decreased competitive fitness during growth. Overall, this study is the first to shed light on the possible genetic strategies supporting the acquisition of HHP resistance in E. coli O157:H7.

Lower limb direct skeletal attachment. A Yucatan micropig pilot study.

Regardless of the type of prosthetic lower limb, successful ambulation requires proper prosthetic attachment. To help alleviate many of the problems associated with prosthetic attachment, direct skeletal attachment (DSA) has been proposed as an alternative to conventional sockets. The purpose of the current study was to evaluate the feasibility of lower limb DSA in a micropig model and to develop a systematic approach to the development and analysis of DSA systems. The DSA device consisted of two stages. The load-carrying stage embedded in the bone canal was designed using bone remodeling theory in conjunction with finite element analysis to approximate implant-induced remodeling and stabilization out to 36 months postimplantation. The skin-interfacing stage was designed to maintain an immutable infection barrier where the prosthesis exited the body. Following successful design, fabrication, and benchtop evaluation, the device was surgically implanted in a Yucatan micropig. The animal trial was successful out to 10 weeks and revealed potential flaws in the surgical protocol related to thermal necrosis. However, no signs of infection were present at the time of implant retrieval. While results of this pilot study support the feasibility of a DSA approach to prosthetic limb attachment, additional animal trials are necessary to prove long-term viability.

[Health-economic assessment of combination therapy for rheumatoid arthritis with methotrexat and etanercept based on the TEMPO Study]. / Gesundheitsökonomische Bewertung der Kombinationstherapie der rheumatoiden Arthritis mit Methotrexat und Etanercept auf der Basis der TEMPO-Studie.

BACKGROUND: The TEMPO study has shown that the combination of etanercept and methotrexat (MTX) in the treatment of rheumatoid arthritis (RA) is superior to monotherapy. It further suggested that remission of RA is a realistic treatment objective. A health-economic assessment of the combination needs to demonstrate the suitability of the combination for daily clinical practice taking economic aspects into consideration. PATIENTS AND METHODS: For the 686 patients in the TEMPO study, a re-analysis was carried out in the form of a Monte-Carlo-Markov-Chain simulation. Study types were cost-effectiveness analysis and cost-utility analysis. Comparators were combined etanercept and MTX vs. MTX alone; the perspective was that of society as a whole. RESULTS: The incremental cost-effectiveness ratio of the combination is 21,300 per life year in remission as compared with MTX alone. The incremental cost-utility ratio of the combination is 38,700 per quality-adjusted life year. CONCLUSION: Both health-economic parameters suggest to adopt the combination therapy into daily clinical practice of RA patients.

Health-economic comparison of three recommended drugs for the treatment of osteoporosis.

Osteoporosis is a large and growing disease with significant health consequences. Based on an evaluation of clinical evidence, the German osteology umbrella organization DVO (Dachverband Osteologie deutschsprachiger wissenschaftlicher Fachgesellschaften) published guidelines in March 2003 for the diagnosis and treatment of osteoporosis. For prevention of fractures in women with postmenopausal and senile osteoporosis, these guidelines recommend three treatment options as first-line therapy: risedronate, alendronate and raloxifene. No evidence is currently available for the reduction of hip fractures by raloxifene. Only risedronate and alendronate, therefore, are recommended for prevention of hip fractures. Information on the cost-effectiveness of preventing and treating osteoporosis may support decision makers in more efficient allocation of resources. Accordingly, the objective of this study is the comparative assessment of the cost-effectiveness of risedronate, alendronate and raloxifene for patient populations in Germany at high risk of osteoporotic fracture due to low bone mineral density (BMD) (i.e., T-score < -2.5) and resulting from a history of at least one previous vertebral fracture, as compared to osteoporotic patients with no treatment. Target variables for the economic comparison are costs per hip fracture avoided and costs per quality-adjusted life year (QALY) gained. Hip fractures are the most costly and best-documented complication of osteoporosis. A cost-effectiveness analysis was therefore conducted, using as criteria for evaluating intervention the incremental cost per hip fracture avoided and the cost per QALY gained. We used a fracture-incidence-based Markov model of osteoporosis, with analysis of patients' transition across outcome states over time (e.g., fracture, healthy, dead). Base-case analysis was conducted on a cohort of 1,000 women aged 70 with low spine BMD and prevalent vertebral fracture, over 3 years of treatment with risedronate, alendronate or raloxifene, and with application of a 10-year analytic time horizon. Model inputs included hip and vertebral fracture incidence rates; relative risk of fracture given low BMD and prevalent vertebral fracture, fracture cost, treatment prices/day (risedronate: 35 mg, 1.76 euro; alendronate: 70 mg, 1.82 euro; raloxifene: 60 mg, 1.82 euro); health utility; and efficacy in terms of relative-risk reduction of fracture of the hip (60% risedronate; 51% alendronate; not significant raloxifene) and vertebrae (49% risedronate; 47% alendronate; 30% raloxifene). A 5% discount rate was applied to cost and outcomes. In the base case, treatment with risedronate reduces costs from the social insurance perspective with respect to both endpoints: i.e., costs per averted hip fracture and QALY. Over the 3-year treatment period and 10-year observation, furthermore, risedronate proved superior to alendronate and raloxifene (i.e., risedronate was less expensive and more effective). From the perspective of statutory health insurance, the cost per averted hip fracture is 37,348 euro for risedronate and 48,349 euro for alendronate (costs for raloxifene were not calculated due to a nonsignificant effect on prevention of hip fractures); and cost per QALY gained is 32,092 euro for risedronate, in comparison to patients in Germany with no therapy (alendronate 41,302 euro; raloxifene 1,247,119 euro). This cost-effectiveness analysis gives evidence that bisphosphonates are cost effective. Under consideration of current prices and the published clinical evidence, risedronate dominates the comparison of DVO-recommended drugs.

[Contribution of leflunomide to the cost effectiveness of sequential DMARD therapy of rheumatoid arthritis in Germany]. / Wirtschaftlichkeit von Leflunomid bei sequentieller Basistherapie der rheumatoiden Arthritis in Deutschland.

Since November 1999, leflunomide (LEF), an innovative disease-modifying antirheumatic drug (DMARD), is available in Germany for treatment of rheumatoid arthritis (RA). LEF slows radiographic disease progression and improves functional capacity as well as healthrelated quality of life of RA patients. Resources for health care of the patients are limited in Germany as in all other countries. The purpose of the analysis therefore was to compare the cost effectiveness of the following alternatives: LEF in sequential monotherapy with other DMARDs versus sequential monotherapy of other DMARDs. The target variables of this cost-effectiveness comparison were additional direct costs per ACR20-response year (ACR20RY) gained and per quality-adjusted life year (QALY) gained, respectively, each after three years of treatment. The cost-effectiveness comparison was carried out using a modeling study after secondary analysis of relevant data. Oral methotrexate (MTX), sulphasalazine (SSZ), antimalarials (CQ/HCQ), intramuscular gold (IMG), and azathioprine (AZA) were selected as "other" DMARDs representing the current status of sequential monotherapy. Based on health care regulation in Germany-Guidelines on the Prescription of Drugs amended by the Federal Commission of Medical Practitioners and Health Insurance Funds on 10 December 1999-LEF was exclusively considered second within a DMARD sequence. Direct costs were given by outpatient and inpatient treatment, long-term care, and rehabilitation treatment. Prices relate to the period of 1998 to 2001 and were converted to Euro (euro), according to the official exchange rate of 1 euro = 1.95583 DM (1 euro approximately 0.90 US dollars; 2001 values). The comparative cost-effectiveness analysis covered a treatment period of more than one year. To estimate the net present value of future costs and effectiveness, a discount rate of 5% per year was applied. In the case of DMARD-naïve patients with RA, the sequence MTX, LEF, SSZ, IMG, AZA, CQ/HCQ was the most cost effective with direct costs of 7297 euro per ACR20RY and 6499 euro per QALY. In order to estimate the consequences of introducing LEF into the prescribing practice in Germany, the distribution of RA patients by individual DMARD in rheumatological care in 1998 was considered. This distribution was taken from the National Database of the German Collaborative Arthritis Centres. Though the sequences comprising LEF incurred 3% higher direct costs, they led to a higher effectiveness of 6% and 3% in the case of ACR20RYs and QALYs, respectively. Choosing sequences comprising LEF, there were additional direct costs of 5004 euro per ACR20RY gained and 8301 euro per QALY gained, as compared to the corresponding sequences without LEF. In comprehensive sensitivity analyses, the robustness of the model and its results was shown. The contribution of LEF to the cost effectiveness of sequential DMARD therapy is obvious. The modeling study revealed advantages for the patients and the cost carriers. Though there were initially higher medication costs of the sequences comprising LEF, these costs were nearly compensated to remaining excess costs of just 3% after three years. This was caused by cost savings in other sectors of the health care system due to the higher effectiveness of the sequences comprising LEF.

Pharmacoeconomic analysis of osteoporosis treatment with risedronate.

Hip fracture is an important and costly problem. Therapy with the bisphosphonate risedronate effectively prevents hip and other fractures among women with established osteoporosis. Risedronate is a first-choice therapy option in the German Guidelines of the Dachverband Osteologie for Osteoporosis according to evidence-based medicine criteria for the treatment of postmenopausal osteoporosis, osteoporosis of the elderly (women aged > 75 years) and glucocorticoid-induced osteoporosis. There are few published economic evaluations of bisphosphonates in Germany. Therefore, an assessment of the cost-effectiveness of risedronate utilizing a state transition Markov model of established postmenopausal osteoporosis based on randomized clinical trial data was developed. Uncertainty underlying model parameters and outcomes was dealt with using traditional sensitivity analysis and stochastic sensitivity analysis to produce quasi-95% Cls. We focused on patients aged 70 years, since this population most closely matches the randomized controlled trial and is typical of osteoporosis patients in Germany. The baseline model was a cohort of 1,000 70-year-old women, who received risedronate for 3 years and were followed up for an overall observation period of 10 years, modelling transitions through estimated health states and evaluating outcomes. Over the 3-year treatment period and 10-year observation period, risedronate dominated the current average basic treatment in Germany. In the risedronate group 33 hip fractures were averted and 32 quality-adjusted life years (QALYs) were gained (discounted values). Risedronate treatment saves costs for German social insurance: the present net value of the associated costs from the perspective of German social insurance is [symbol: see text]10.66 million if risedronate treatment is used versus [symbol: see text]11 million if basic treatment is used. Thus, net savings of [symbol: see text]340,000 for the treatment group per 1,000 treated women were calculated. Furthermore, risedronate treatment is cost effective from the perspective of the statutory health insurance with costs per averted hip fracture in the analyzed population of [symbol: see text]33,856 and cost per QALY gained of [symbol: see text]35,690. Both results demonstrate cost-effectiveness and are far below the accepted threshold level of [symbol: see text]50,000. Based on this analysis, risedronate is a cost-effective treatment for postmenopausal osteoporosis within the German health care system, offering benefits for osteoporotic patients and for budget decision-makers.

Cost effectiveness of ramipril in patients with non-diabetic nephropathy and hypertension: economic evaluation of Ramipril Efficacy in Nephropathy (REIN) Study for Germany from the perspective of statutory health insurance.

BACKGROUND: In the Ramipril Efficacy In Nephropathy (REIN) trial, ramipril significantly lowered the rate of reaching the combined end-point of doubling of baseline serum creatinine levels or end-stage renal failure (ESRF). OBJECTIVE: To determine the additional cost per patient-year of chronic (long term) dialysis avoided (PYCDA) when the ACE inhibitor, ramipril, was added to conventional treatment of patients with non-diabetic nephropathy and hypertension. STUDY PERSPECTIVE: Statutory Health Insurance (SHI) provider in Germany. DESIGN AND SETTING: Data from the REIN Study were used in a cost-effectiveness analysis (CEA). A modelling approach was used, which was based on secondary analysis of published data, and costs were those incurred by the SHI provider (i.e. SHI expenses). In the base-case analysis, average case-related SHI expenses were applied and PYCDA were quantified using the cumulative incidence of ESRF as observed in the REIN trial. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios (ICERs) of ramipril varied between about -76,700 deutschmarks (DM) and -DM81,900 per PYCDA (DM 1 approximately equals 0.55 US dollars; 1999 values), according to the treatment periods of 1 year and 3 years, respectively. In the sensitivity,analysis, the robustness of the model and its results were shown when the extent of influence of different model variables on the base-case results was investigated. First, probabilities of ESRF and PYCDA were estimated according to the Weibull method. Second, the influence of the model variables on the target variable was quantified using a deterministic model. Third, the dependency of the target variable (ICER) on random variables was described in a simulation. The cost for chronic dialysis had by far the greatest impact on the target variable, which was 28 times greater than the impact of clinical effectiveness of ramipril, i.e. the number of PYCDA. There were net savings per PYCDA with ramipril treatment after 1, 2 and 3 years: 95% of the 10,000 simulation steps resulted in savings of between DM69 500 and D94,600 per PYCDA after 3 years. CONCLUSIONS: Results from this evaluation show that ramipril offers enormous savings from the perspective of the SHI provider (third-party payer) in Germany when added to the conventional treatment of patients with non-diabetic nephropathy and hypertension.

Chlorine Concentration and the Inoculation of Tomato Fruit in Packinghouse Dump Tanks.

Chlorine concentrations (pH 6 to 7 and 22 to 27°C) that killed arthrospores (spores) of Geotrichum candidum or sporangioles (spores) of Rhizopus stolonifer, causal agents of sour rot and Rhizopus rot, respectively, in moving water within 30 to 45 s did not prevent these pathogens from inoculating wounded tomatoes (Lycopersicon esculentum) in a water flume containing chlorine and spores. Free chlorine concentrations of 20 or 25 mg/liter were lethal to spores of G. candidum within 30 s in most in vitro tests, whereas spores of R. stolonifer were slightly less sensitive. Wounded tomatoes placed in a flume with free chlorine at 30 mg/liter and then exposed to spores for 1 min developed about 50% less decay incidence during storage at 24°C for 6 days than did fruit exposed to spores and water alone. In the absence of chlorine, incidence averaged 57% (range, 15 to 95%) for R. stolonifer and 38% (range, 17 to 58%) for G. candidum. Sporadic sour rot lesions were observed among fruit that had been treated with free chlorine at 75 mg/liter, whereas chlorine at up to 180 mg/liter failed to completely protect fruit from Rhizopus rot. A water-soluble dye rapidly penetrated wounds on tomato fruit. The dye framed the outlines of cells at the wound surface and appeared to penetrate into a few intercel-lular spaces. Application of 1% sodium hypochlorite decolorized the dye on the wound surface, whereas deposits located below the wound surface remained blue. Thus, spores suspended in moving water can escape the action of chlorine if carried into intercellular spaces by diffusion or by capillary movement of cell sap and water.

Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany.

OBJECTIVE: To use published data to compare the economic consequences of specific immunotherapy (SIT) lasting 3 years with those of continuous symptomatic treatment in patients with either pollen or mite allergy. DESIGN AND SETTING: The evaluation was conducted from the following 3 perspectives in Germany: (i) society; (ii) healthcare system; and (iii) statutory health insurance (SHI) provider. A modelling approach was used which was based on secondary analysis of existing data. The follow-up period was 10 years. The break-even point of cumulated costs, their difference per patient and the additional cost per additional patient free from asthma symptoms [incremental cost-effectiveness ratio (ICER)] were used as target variables, each from the viewpoint of SIT. The types of costs were direct and indirect (society), direct (healthcare system) and those incurred by SHI (i.e. expenses). In the base-case analysis, the average values of the clinical parameters and average case-related costs/expenses were applied. MAIN OUTCOME MEASURES AND RESULTS: The break-even point was reached between year 6 and year 8 after the start of therapy, resulting in net savings of between 650 and 1190 deutschmarks (DM) per patient after 10 years. The ICERs of SIT were between -DM3640 and -DM7410, depending on study perspective and nature of the allergy (1990 values for symptomatic treatment and treatment of asthma, 1995 values for SIT; DM1 approximately $US0.58). The sensitivity analysis demonstrated the robustness of the model and its results. First, all the independent variables of the model were varied. Secondly, the influence of the model variables was quantified using a deterministic model. SIT was more likely to result in net savings than in additional costs. An economic parameter (cost for symptomatic treatment) had the highest influence on the results. CONCLUSIONS: This evaluation showed that SIT for 3 years is economically advantageous in patients who are allergic to pollen or mites and whose symptoms are inadequately controlled by continuous symptomatic treatment. After 10 years, the administration of SIT leads to net savings from the perspectives of society, the healthcare system and SHI (third-party payer) in Germany.

[Radiotherapy of humero-scapular periarthritis using ultra-hard photons. Evaluation by MRI findings]. / Strahlentherapie der Periarthritis humeroscapularis mit ultraharten Photonen. Vergleich mit kernspintomographischen Befunden.

PURPOSE: Evaluation of MRI in radiotherapy of humeroscapular periarthritis. PATIENTS AND METHODS: Seventy-seven patients with humeroscapular periarthritis prospectively underwent MRI before radiotherapy. RESULTS: Six months after radiotherapy, 34% of the patients had achieved complete pain relief, 35% major pain relief. Twenty percent had only slight improvement and 12% no improvement. Positive correlation of radiotherapy outcome and MRI findings could be shown for acute tendinitis, erosions, and complete and incomplete ruptures of the supraspinatus tendon. CONCLUSIONS: Radiotherapy is highly effective in the treatment of humeroscapular periarthritis. The indication can be improved using MRI.

The cost effectiveness of acamprosate in the treatment of alcoholism in Germany. Economic evaluation of the Prevention of Relapse with Acamprosate in the Management of Alcoholism (PRAMA) Study.

Alcoholism places a considerable economic burden on society. The rate of relapse of previously weaned alcoholics has been shown to decrease following treatment with acamprosate. Therefore, this study investigated the cost effectiveness of acamprosate in the treatment of alcoholism in Germany from the perspective of the German healthcare system. In this retrospective analysis of clinical data, the additional direct medical costs per additional abstinent alcoholic incurred by adjuvant acamprosate therapy of previously weaned alcoholics were quantified. In the base-case analysis, average case-related direct costs were applied. The cost-effectiveness ratio was -2600 deutschmarks (DM) per additional abstinent patient. Thus, the administration of acamprosate is cost saving. The cost benefit of acamprosate was also shown in a sensitivity analysis. The variance of the target variable under 'real world' conditions was simulated and the impact of the model variables on the target variable was quantified using a deterministic model. The variance was broad and the rate of abstinence under acamprosate was the independent variable with the greatest impact on the target variable. From the perspective of both the German healthcare system (i.e. direct medical costs) and the Statutory Health Insurance expenses, adjuvant acamprosate therapy led to net savings, while at the same time improved the patient's state of health. Based on the naturalistic design of the underlying clinical trial and on this economic evaluation, it can be concluded that adjuvant acamprosate therapy leads to net savings under 'real world' conditions.

Economic evaluation of the Cardiac Insufficiency Bisoprolol Study for the Federal Republic of Germany.

The Cardiac Insufficiency Bisoprolol Study (CIBIS) demonstrates that, for patients with heart failure of different aetiologies, administration of the beta 1-adrenoceptor blocker bisoprolol as an adjuvant to the standard therapy leads to a significant avoidance of hospital admissions. A pharmacoeconomic analysis of the results of the CIBIS was conducted for the Federal Republic of Germany, and was restricted to direct costs only. The costs of bisoprolol medication and inpatient treatment of heart failure were considered, the latter forming the major part of costs incurred. Per 1000 patient-years, adjuvant bisoprolol therapy resulted in overall cost savings of Deutschmarks (DM)157,272. Statutory Health Insurance had a net saving of DM186,719 in 1000 patient-years, while patients experienced additional net expenses of DM17,760 over 1000 patient-years. The economic advantage of adjuvant bisoprolol treatment was also borne out in the sensitivity analysis. Adjuvant therapy with bisoprolol was not only clinically beneficial for the patient with heart failure but was also economically advantageous.

Cost-effectiveness analysis of ramipril in heart failure after myocardial infarction. Economic evaluation of the Acute Infarction Ramipril Efficacy (AIRE) study for Germany from the perspective of Statutory Health Insurance.

OBJECTIVE: Data from the Acute Infarction Ramipril Efficacy (AIRE) study were used in a cost-effectiveness analysis to determine the incremental cost per life-year gained (LYG) when the ACE inhibitor ramipril was added to conventional treatment in patients with heart failure after acute myocardial infarction. In the AIRE trial, the addition of ramipril significantly lowered rates of total mortality and rehospitalisation due to heart failure. DESIGN AND SETTING: The cost-effectiveness analysis was conducted from the perspective of the Statutory Health Insurance (SHI) provider in Germany. A modelling approach was used which was based on secondary analysis of existing data, and costs were those incurred by SHI (i.e. expenses of SHI). In the base-case analysis, average case-related expenses of SHI were applied and LYG were quantified by the method of Kaplan and Meier. MAIN OUTCOME MEASURES AND RESULTS: The incremental cost-effectiveness ratios of ramipril varied between 2500 and 8300 deutschmarks (DM) per LYG (1993 values for inpatient and 1995 values for outpatient treatment; DM1 approximately $US0.70), according to the treatment periods of 3.8 years and 1 year, respectively. In the sensitivity analysis, the robustness of the model and its results was shown when the extent of influence of different model variables on the base-case results was investigated. First, survival probability and LYG were estimated according to the Weibull method. Second, the dependency of the target variable (i.e. incremental cost per LYG) on random variables was described in a simulation. Third, the influence of the model variables on the target variable was quantified using a deterministic model. The variance of the target variable was broad and the hospitalisation impact of adding ramipril to conventional treatment was an independent variable with much greater influence on the target variable than the parameter of clinical effectiveness, i.e. the number of LYG. CONCLUSION: Results of this evaluation showed that ramipril has a favourable incremental cost-effectiveness ratio for the treatment of heart failure in post myocardial infarction patients and can be considered an economical therapeutic agent from the perspective of SHI (third-party payer) in Germany.

[Cost effectiveness of bisoprolol in heart failure. Economic evaluation of the Cardiac Insufficiency Bisoprolol Study (CIBIS) for Germany]. / Wirtschaftlichkeit von Bisoprolol bie Herzinsuffizienz. Okonomische Bewertung der Cardiac Insufficiency Bisoprolol Study (CIBIS) für die Bundesrepublik Deutschland.

BACKGROUND: The Cardiac Insufficiency Bisoprolol Study (CIBIS) demonstrates that, for patients with heart failure of different etiologies, the administration of the beta(1)-adrenoceptor blocker bisoprolol adjuvant to the standard therapy leads to a significant avoidance of hospital admissions. PHARMACOECONOMIC EVALUATION: The results of the CIBIS were evaluated pharmacoeconomically for the Federal Republic of Germany, and were restricted to direct costs only. The costs of bisoprolol medication and in-patient treatment of heart failure were considered, the latter forming the major part of costs incurred. CONCLUSION: Adjunctive therapy with bisoprolol is not only clinically beneficial to the patient with heart failure, but also economically advantageous.

[Cost-effectiveness analysis of prevention of reinfarction using low-dose acetylsalicylic acid; model calculation]. / Kosten-Wirksamkeits-Analyse der Reinfarktprophylaxe mit niedrig dosierter Acetylsalicylsäure: Modellrechnung.

The purpose of this study is to estimate the potential of savings which can be achieved by prophylaxis of myocardial reinfarction with low-dose acetylsalicylic acid (ASA) at 75 mg per day over a treatment period of two years. After secondary analysis of published data, the effectiveness of low-dose ASA is compared to placebo by a model calculation. The difference in the effectiveness between the prophylaxis with ASA and placebo is taken from an international meta-analysis. The economic valuation of this difference is carried out by a cost-effectiveness analysis applying disease costs per case. According to the model calculation, 5535 DM can be saved per patient with a history of myocardial infarction with 75 mg ASA a day over a treatment period of two years. In 1991 there were around 740,000 patients with a history of myocardial infarction in the age group of 25-64 in the Old Bundesländer of the Federal Republic of Germany. The application of the results of the model calculation would lead to considerable savings. Even in the sensitivity analysis with different assumptions regarding costs incurred by hospital treatment and costs incurred by premature retirement, the cost advantage of the ASA-prophylaxis remains. Due to the cautious and conservative assumptions in the model calculation the potential of savings is likely underestimated. Nevertheless, there is a distinct advantage for the prophylaxis with low-dose ASA which already occurs in direct costs thus leading to advantages also for cost carriers.

Alcoholism. The cost of illness in the Federal Republic of Germany.

The purpose of this study was to estimate the direct and indirect costs of alcoholism in the Federal Republic of Germany. Direct costs comprised treatment costs, while indirect costs consisted mainly of costs incurred as a result of work time lost, as well as costs related to premature retirement and premature mortality. The costs of alcoholism were estimated using the aggregated statistics of several social security organisations and official statistics. For the purposes of this study, alcoholism was defined as alcohol dependence syndrome [9th revision of the International Classification of Diseases code (ICD) 303], alcoholic chronic liver disease and cirrhosis (ICD 571.0 to 571.3), and alcoholic psychoses (ICD 291). The reference period consisted of the years 1985 to 1991. All statistics and all analyses were limited to the so-called old states of Germany, within the boundaries as they were before 3rd October 1990. The overall monetary burden (in 1990 Deutschemarks) of alcoholism in the western part of Germany in 1990 was estimated to be DM5975 million. Alcoholism is associated with considerably more indirect costs (DM4422 million) than direct costs (DM1553 million). The predominance of indirect costs is mainly the result of the very high premature mortality of patients with alcoholism. Thus, the cost of premature mortality makes up more than half of the indirect costs of alcoholism (DM2284 million), while about a quarter of the indirect costs (DM1150 million) are associated with inability to work. Early retirement accounts for a similar amount (DM988 million). The majority of direct costs is accounted for by treatment in acute hospitals (DM869 million). Costs incurred as a result of rehabilitation treatment (DM373 million) and ambulatory care (DM331 million) are also considerable.

Decreased balance performance in cowboy boots compared with tennis shoes.

OBJECTIVE: This study was conducted to examine the relative balance performance of cowboy boots versus tennis shoes when the subject was challenged with different accelerations. The end point was the highest acceleration at which the subject could maintain full foot contact with the platform for each footwear type, ie, break acceleration. DESIGN: Crossover trial. SETTING: General community. PARTICIPANTS: Twenty-seven healthy women, 18 to 40 years old, with shoe sizes between 6 and 9, were selected in a convenience sample after their response to posted ads in a university medical center. INTERVENTION: Each subject was tested 3 times in the forward direction per acceleration on a Motionspec balance platform. A successful series was defined as keeping feet flat for 2 of 3 tests/level. MAIN OUTCOME MEASURE: The planned major outcome was the difference between the highest accelerations at which the subject was successful for each type of footwear. RESULTS: Subjects were found to have a highest sustainable acceleration in boots 10.66 +/- 6.20cm/s2 less than the highest acceleration in shoes. A period effect was found that improved the results of the second footwear tested by 7.2 +/- 6.20cm/s2. CONCLUSIONS: Cowboy boots have a decreased balance performance compared with tennis shoes. Further study should examine the specific features in the boot that contribute to this imbalance and examine the kinematic adaptations of the body to cowboy boots.