[§ 116b SGB V (social insurance code, book five) for rheumatology patients. An empirical assessment on the basis of administrative data]. / § 116b SGB V in der rheumatologischen Versorgung. Eine empirische Abschätzung anhand von Routinedaten.

BACKGROUND: The choice between outpatient and inpatient care is currently undergoing major changes within the German health care system with the amendment of § 116b SGB V. This study investigates what proportion of hitherto inpatient rheumatologic care could potentially be given on an outpatient basis. METHODS: The analysis is based on administrative inpatient data from 2004 to 2008 covering approximately 23.6 million private health insurance insurants. The selection of patients with rheumatological diseases was based on diagnosis according to ICD-10 of § 116b SGB V. RESULTS: From 2004 to 2008 the number of all rheumatologic cases increased by 13.9%, while the average length of hospital stay decreased from 9.46 days to 8.08 days and the number of attending hospitals declined by 3.1%. The number of rheumatologic cases with a short inpatient stay (≤2 days) increased by 32.3%. We define the ambulatory potential as the proportion of patients with a short length of stay to the total of inpatient rheumatologic cases; this increased from 25.7% to 29.9%. DISCUSSION: Not all patients with a short inpatient stay can be transferred problem-free to ambulatory care. No channeling of patients to specialized centres has taken place thus far in Germany. Quality of care at the hospitals studied has not been considered. Further data are needed to link administrative data with quality care data.

[Analysis of mortality and convergence tendencies in inpatient care of stroke and myocardial infarction]. / Analyse von Mortalitäten und Konzentrationstendenzen in der stationären Versorgung von Schlaganfall und Myokardinfarkt.

BACKGROUND: An increase in the convergence of medical services toward specialized hospitals with high case numbers as well as the effects on quality of care are often assumed to be the result of diagnosis-related groups (DRGs; case-based lump-sum reimbursement). Estimates of the extent to which these effects occur in emergency diagnoses are not available. METHODS: Claims data relating to approximately 23.6 million insured within the period 2004-2007 (inclusive) were analyzed. All cases with the main diagnosis of stroke (ICD-10: I63 and I64) and myocardial infarction (ICD-10: I21) were included in the study. RESULTS: Increasing case numbers could be observed for all entities within the period studied (myocardial infarction: +12.71%; stroke: +1.73%). The absolute increase in case numbers seems to affect those hospitals with case numbers >100 per year, whereas case numbers of hospital groups including hospitals with low case numbers per year remain unchanged or grow slower. No absolute trend in mortality could be seen. However, a disproportionate rate of mortality in hospitals with low case numbers per year for both diagnoses was observed. CONCLUSION: The convergence of emergency treatment in a few specialized centers has not yet been accelerated by the implementation of DRGs. Essentially, relative changes can be seen due to case number increases in large centers rather than because of service cutbacks and shifts from smaller hospitals. The reason for this could be the need to maintain emergency care in rural regions, while specialized centers are increasingly built in urban areas.

[Analysis of selection inventives for health insurances after introduction of the morbidity-oriented risk compensation scheme: an empirical analysis]. / Analyse von Selektionsanreizen für Krankenkassen nach Einführung des morbiditätsorientierten Risikostrukturausgleichs: Eine empirische Analyse.

BACKGROUND: The risk compensation scheme (RCS) in the Statutory Health Insurance (SHI) was implemented in 1994 to discourage risk selection between sickness funds. However, several expertise papers have concluded since then that the sociodemographic risk adjusters in place could not adequately curb risk selection. To minimise incentives for risk selection in the Statutory Health Insurance (SHI) further, the RCS was refined in 2009 by adding 80 diseases as additional risk adjusters. In spite of the better compensation of differences in morbidity, however, incentives for risk selection may still persist. In this study, we investigated the association of indicators such as region (number of inhabitants in the city), income, level of education and family status (children in the household) with health care costs to determine if risk selection is still attractive for sickness funds under the refined RCS. METHOD: The analysis is based on a 2002 cross-section survey comprising 75,122 individuals. Health expenditures were estimated using self-documented utilisation data and were standardised for age, sex and diagnoses covered by the risk adjustment scheme. We included costs for inpatient care, outpatient care, pharmaceuticals, rehabilitation, and medical devices. To assess the effects of the above-mentioned individual characteristics on health-care expenditure, regression analyses and analyses of variances were performed. RESULTS: Full documentation was available for 52,484 individuals (69.86%). From these the variables "family status (children in the household)", "higher educational level", and "higher income" were associated with lower costs for individuals without chronic conditions. For individuals with chronic conditions, results were mixed. "Family status", "education" and "income" showed no clear association with lower or higher costs and were not statistically significant. The variable "region" was neither significantly associated with chronically ill nor for healthy individuals. DISCUSSION: With respect to age, sex, and morbidity, individuals with high income and education and without chronic diseases apparently cause lower costs. Thus, health status, income and education remain as possible selection criteria for sickness funds in Germany. However, the refined RCS compensates for the largest proportion of cost differences between insured with and without chronic disease. Possible causes of the small but remaining differences and whether improving preventive programmes or providing awareness campaigns may be appropriate strategies to tackle this issue should be investigated in future research.

[Convergence tendencies in inpatient oncological care after implementation of diagnosis-related groups in Germany]. / Konzentrationstendenzen in der stationären onkologischen Versorgung nach Einführung von Diagnosis-Related Groups in Deutschland.

BACKGROUND: An increase of the convergence of medical services towards specialised hospitals with high case numbers is often assumed as a result of the implementation of diagnosis-related groups (DRG; case-based lump sum reimbursement). So far, estimates of the extent to which this effect occurs after the recent implementation of DRGs are not available in Germany. METHOD: Claims data of about 23,600,000 insured within the inclusive period 2004-2007 were analysed. All cases with the main diagnosis of lung cancer, prostate cancer, and colorectal cancer were included in the study. Broken down by entities and years, graphical and statistical concentration measures as well as the percentages of different hospital size classes were calculated. RESULTS: Increasing case numbers could be observed for all entities within the period (lung cancer:+25.7%; prostate cancer:+12.5%; colorectal cancer:+8.1%). The concentration measures showed hardly any changes in the course of time. The absolute increase of case numbers seems to affect those hospitals with case numbers higher than 50 per year above average [lung cancer cases in a hospital group including hospitals with more than 50 cases 2004 (percentage): 78.1% and 2007: 81.6%; prostate cancer: 67.4% and 71.7%; colorectal: 72.5% and 75.9%], whereas case numbers of hospital groups including hospitals with case numbers less than 50 per year remain unchanged or grow more slowly. DISCUSSION: The convergence of oncological services towards a few specialised centres has not yet been accelerated by the implementation of DRG's. Fundamentally, relative changes can be noticed due to case number increases in large centres, not because of service cutbacks and shifts from smaller hospitals. Reasons for this could either be the inflexibility of capacity planning or control options of the statutory health insurance. CONCLUSION: Further research of convergence tendencies and its drivers is required to be able to draw any benefit from efficiency and quality potentials.

Complement activation and fibrinolysis during infection with Theileria parva (East Coast fever) in cattle.

The role played by complement and fibrinolysis in the pathogenesis of pulmonary oedema and the disseminated, subendothelial, petechial haemorrhages in cattle infected with Theileria parva was investigated. There was a marked reduction in total haemolytic complement in animals that died of this disease whereas the survivors showed only transient changes. The reduction in C3 levels in animals with severe disease, however, was equivalent to that in the survivors. Neither circulating soluble immune complexes nor free antibody against macroschizonts were detected in sera from cattle with severe infection. In addition to the complement changes, high levels of fibrinogen degradation products (FDPs) were detected in sera from the infected animals. The rate of production of FDPs and reduction in total haemolytic complement paralleled the clinical course of the disease. It is, therefore, suggested that the pulmonary oedema and disseminated petechial haemorrhages seen in East Coast fever may be the direct result of the combined effects of complement activation and consumption of fibrinogen and fibrin.

Salivary gland of the tick vector of East Coast fever. IV. Cell type selectivity and host cell responses to Theileria parva.

Responses of cells in the tick salivary gland to parasitism by Theileria parva were studied by electron microscopy. The gland is composed of three distinct types of acini (I, II, III) which together include ten or more different cell types. Of some 30 infected cells observed in the present study, all were E-cells of acinus III. The parasite thus exhibits a high degree of selectivity for acinus and cell type. The glandular cell invaded undergoes massive hypertrophy and accumulates glycogen deposits in its cytoplasm which may serve as an energy source for the growing intracellular parasite. As synthesis of its secretory material declines the product is packaged in progressively smaller secretory granules. The extensive arrays of endoplasmic reticulum are dismantled and eliminated in autophagic vacuoles. Excess secretory granules are also broken down by crinophagy. After 4 days, sporogony is completed and the host cell contains 30,000-50,000 sporozoites in an electron-lucent cytoplasm largely devoid of cytomembranes and secretory granules. Mitochondria are still present and normal in appearance. The loss of basophilia and secretory granules observed heretofore by light microscopy have been attributed to ingestion and destruction of host organelles by the parasite. The pallid appearance of the cytoplasm has been interpreted as a sign of impending degeneration of the host cell. In electron micrographs no ingestion of organelles by the parasite or degenerative changes were found. The host cell clearly remains viable and metabolically active throughout sporogony. The striking changes in its ultrastructure result from active elimination of organelles and inclusions by the host cell itself in response to parasitism.

Salivary gland of the tick vector of East Coast fever. III. The ultrastructure of sporogony in Theileria parva.

Sporogony of the sporozoan Theileria parva in the salivary gland of the tick vector of East Coast fever was studied in electron micrographs. The findings differ in several respects from previous interpretations based upon light microscopy. Cytokinesis of the primary sporoblast to form secondary and tertiary sporoblasts is not substantiated. Instead it is suggested that the parasite develops as a ramifying, multinucleate syncytium rapidly increasing in size and complexity until it gives rise to myriad sporozoites in a terminal episode of cytoplasmic fission. The proliferating nuclei initially occupy peripheral lobules that are continuous with a central labyrinth of branching and anastomosing processes which present a very large surface area for interchange of metabolites with the host cell cytoplasm. The membrane of the labyrinth is rich in cytostomes, but no evidence if found to bulk uptake of host cytoplasmic matrix or organelles into food vacuoles. Rhoptries are the first of the polar organelles of the parasite to develop and are associated with dense plaques irregularly distributed on the inner aspect of the parasite membrane. Micronemes form independently of the rhoptries at a later stage. After 3-4 days of tick feeding, sporogeny is complete and the infected salivary gland cell contains up to 50, 000 spherical or ovoid sporozoites about 1 micrometer in diameter. These are limited by a simple plasma membrane. The inner layer of the 'pellicle', the polar ring, and the conoid described for zoites of other Apicomplexa are lacking. Maturational changes are noted in sporozoites after sporogony is completed. Micronemes appear to increase in size, and possibly in number, from days 3-5 and the majority take up positions immediately subjacent to the plasmalemma.

Salivary gland of the tick vector (R. appendiculatus) of East Coast fever. I. Ultrastructure of the type III acinus.

The brown ear tick Rhipicephalus appendiculatus is the vector for East Coast fever, a disease that seriously limits livestock production in East Africa. The sporozoites of the infectious agent Theileria parva develop in the tick salivary gland. This paper describes the organization of the type III acinus of the gland and establishes unambiguous ultrastructural criteria for identification of the three secretory cell types: the d-cell, e-cell and f-cell. These observations are basic to exploration of possible cell-type specificity of the invading theileria and other aspects of host-parasite relations.

Salivary gland of the tick vector (R. appendiculatus) of East Coast fever. II. Cellular basis for fluid secretion in the type III acinus.

Fluid balance is a major physiological problem for hematophagous ticks. To maintain osmotic balance they must conserve water for prolonged periods while seeking a mammalian host, and they must eliminate a very large volume of excess fluid taken in during a relatively short period of feeding. This is accomplished in part by modification of the salivary gland during 7-10 days of feeding to secrete a copious saliva which is pumped into the bovine host. This function has previously been attributed to certain interstitial epithelial cells of the type III acinus which differentiate in the course of feeding into cells reminiscent of those of the avian salt gland. The ultrastructural changes in the type III acinus during the blood-meal were studied. In addition to the differentiation of the interstitial cells, this paper describes a remarkable sequence of changes in external form and internal organization of the e-cells. This results in their transformation from typical protein-secreting glandular cells to transport cells having myriad basolateral processes interdigitating with those of the ablumenal interstitial cells to form a basal labyrinth comparable to that of other fluid-transporting epithelia. The findings are discussed in relation to various postulated mechanisms for fluid and electrolyte transport.

Effects of a mistletoe preparation with defined lectin content on chronic hepatitis C: an individually controlled cohort study.

Despite advances in the therapy of chronic hepatitis C for some hepatitis C virus (HCV) genotypes interferon and ribavirin combination therapy is effective in less than 50% of patients. Abnobaviscum Quercus (AQ) is a mistletoe preparation containing defined amounts of mistletoe lectins (ML). It has shown immunomodulatory properties in vitro and in vivo. In small clinical trials AQ resulted, within an anthroposophical treatment concept, in a biochemical or virological response in up to 40% of patients with chronic hepatitis C. In order to evaluate the effect of this preparation we conducted an individually controlled cohort study. 25 patients with chronic hepatitis C (mean duration 147 +/- 80 months) and elevated alanine aminotransferase (ALT) levels were included in the study. As control they were observed for 6 months pre-treatment. This pre-treatment period was followed by 6 months of active treatment in which the mistletoe preparation was subcutaneously injected three times a week. Main outcome parameters were normalization of ALT and viral load. Hepatitis C associated signs and symptoms like tiredness, fullness in the right upper abdomen and musculoskeletal pain were assessed monthly in a standardized questionnaire. All 25 patients completed the study and most of the patients wanted to continue treatment. Mean duration of treatment was 9.1 months. None of the patients had complete or partial normalization of ALT or HCV RNA levels during pre-treatment or treatment period. Mean ALT did not change during the study. Tiredness, fullness in the right upper abdomen and musculoskeletal pain were present in 18, 8 and 4 patients respectively. They significantly improved within two months of treatment. A significant eosinophilia (p=0.0001) occurred between month 2 and 6 during treatment. 9 month treatment with a ML containing mistletoe preparation has no effect on viral load or ALT as markers of activity in patients with chronic hepatitis C. However, frequency and intensity of clinical signs and symptoms in our patients decreased significantly, similar to reports of improved quality of life in tumour patients treated with such preparations. A significant eosinophilia suggests that ML containing mistletoe preparations induce a T-helper 2 immune response.

The early events of infection with Theileria parva in cattle: infectivity for cattle of leukocytes incubated in vitro with sporozoites.

Leukocytes were isolated from bovine blood and, after short periods of incubation in vitro with sporozoites of Theileria parva, were washed thoroughly, and their infectivity tested in autologous and allogeneic hosts. Using a standard inoculum of 10(6) viable cells, it was found that, after incubation in vitro for either 1 or 24 h, the cells initiated lethal infections in autologous cattle, but failed to infect allogeneic animals. Autologous and allogeneic erythrocytes and mouse lymphocytes similarly incubated with sporozoites failed to infect cattle. The supernatant from bovine lymphocyte suspensions incubated with sporozoites for 1 h produced lethal infections whereas after 24 h of incubation the supernatant was non-infective. All cattle which did not develop detectable infection were fully susceptible to subsequent challenge with a stabilate of sporozoites. By inoculating cattle with graded doses of autologous blood leukocytes which had been incubated for 24 h with sporozoites, it was found that as few as 2 X 10(3) cells gave rise to infection. The results indicate that this approach can be used to evaluate different cell populations as targets for infection and transformation by sporozoites of T. parva.

Titration in cattle of infectivity and immunogenicity of autologous cell lines infected with Theileria parva.

Cell lines infected with Theileria parva were derived by infection of bovine peripheral blood lymphocytes with sporozoites in vitro. Cattle were inoculated with doses of autologous infected cells ranging from 1 X 10(1) to 1 X 10(8). Infection became established in animals which received 1 X 10(2) or more cells. While 1 X 10(2) cells resulted in sub-patent infection with development of immunity to challenge with sporozoites, larger doses of cells gave rise to patent infections of increasing severity. Thus, doses of 1 X 10(5) and 1 X 10(6) cells sometimes produced lethal infections and with 1 X 10(7) and 1 X 10(8) the outcome was invariably lethal. Based on the previous observation that induction of immunity by allogeneic cells requires transfer of infection into the recipient-host cells, a comparison of the infections produced by autologous and allogeneic cells indicated that the transfer of infection from allogeneic cells occurs at a frequency of maximally 1 X 10(-5). Two pairs of cattle were identified as being mutually non-reactive in the mixed leukocyte reaction (MLR). Doses of 1 X 10(6) and 1 X 10(7) cells of cell lines derived from 1 animal of each pair were inoculated into the autologous host, the non-reactive partner and an animal which was shown to be strongly reactive to the donor in the MLR. In each instance, the reaction in the MLR non-reactive recipient was not significantly different from that of the MLR reactive recipient, but was markedly different from that of the autologous recipient.

Blast transformation of adherent macrophages infected in vitro with sporozoites of Theileria parva.

Rhipicephalus appendiculatus ticks were fed on cows with parasitemia from Theileria parva infection (East Coast fever). Homogenates of salivary glands with infective sporozoites were added to cultures of (i) monocyte-derived adherent macrophages from normal bovine peripheral blood and (ii) macrophages from spleen and bone marrow. It was shown by light, phase-contrast, and electron microscopies and by tests for lysosomal enzymes, phagocytosis of carbon particles, and cell markers (fibronectin and Fc receptors) that macrophages transformed in vitro to blast cells containing macroschizonts in 2 to 3 weeks. These blasts detached from the monolayer and grew indefinitely in suspension culture.

Efficacy of milbemycin oxime against fourth-stage larvae and adults of Ancylostoma tubaeforme in experimentally infected cats.

The efficacy of milbemycin oxime against fourth-stage (L4) larvae and adults of Ancylostoma tubaeforme was investigated in a trial involving 24 young domestic shorthair cats. The animals were inoculated with approximately 300 infective stage three (L3) larvae and divided into three groups. After 12 days, eight cats (group 1) were treated with medicated tablets containing 4 mg milbemycin and 10 mg praziquantel to test the efficacy against L4 larvae; eight cats in group 2 were treated with the same tablets after 33 days to test the efficacy against adult worms; and eight cats in group 3 were treated with a placebo tablet. Faecal egg counts were determined periodically in each cat and after 40 or 41 days the number of worms in each animal was determined postmortem. The egg count reduction was determined by comparing the geometric mean numbers of eggs per gram of faeces in the placebo and medicated groups, and the worm reduction by comparing the geometric mean numbers of worms. The egg count reduction was more than 99 per cent in both treated groups, while the number of worms in groups 1 and 2 were reduced by 94.7 per cent and 99.2 per cent, respectively.

The efficacy of triclabendazole and other anthelmintics against Fasciola hepatica in controlled studies in cattle.

In eight controlled tests 274 cattle were used to assess the efficacies of triclabendazole, albendazole, clorsulon, nitroxynil, oxyclozanide and rafoxanide against Fasciola hepatica. Against one-, two- and four-week-old early immature fluke the mean efficacies of triclabendazole given orally at 12 mg/kg were 88.1, 95.3 and 90.7 per cent, respectively. Clorsulon, nitroxynil and rafoxanide administered at recommended dose rates showed negligible activity against these stages of the parasite. Against six- and eight-week-old infections the mean efficacies of triclabendazole at 12 mg/kg were 87.5 per cent and 95.7 per cent, respectively. Against F hepatica aged six weeks, albendazole and oxyclozanide showed no activity and clorsulon, nitroxynil and rafoxanide had only slight to moderate activity. The efficacies of triclabendazole, clorsulon, nitroxynil and rafoxanide against 10- or 12-week-old parasites were 100, 99.0, 99.1 and 90.1 per cent, respectively. Albendazole and oxyclozanide showed poor efficacy against 12-week-old infections.

Life prolonging of disease management programs in patients with type 2 diabetes is cost-effective.

AIM: Our objective was to examine the cost-effectiveness of disease management programs (DMPs) for type 2 diabetes mellitus (T2DM) taking into account their life prolonging effect. METHODS: We compared real life costs in 19,888 propensity score matched pairs of T2DM DMP participants and T2DM patients in routine care (RC) according to sickness funds data. We estimated mean annual costs for survivors, last year of life costs for decedents, the influence of ageing on costs, incremental cost-effectiveness ratio and effects on hospitalization. RESULTS: Annual costs for survivors were 3,318€ (DMP) and 3,570€ (RC). The mean costs in the last year of life were 16,911€ (DMP) and 15,763€ (RC). Ageing had a cost triggering effect for survivors (30€/36€ per year in DMP-/RC-group; p<0.001) and a cost decreasing effect in the last year of life (546€/483€ per year in DMP-/RC-group; p<0.001). The incremental cost-effectiveness ratio of the DMP vs. RC was -1396€ per life-year gained. Hospitalizations increased with age in case of survival and decreased with age in case of death but were always lower in the DMP-group. CONCLUSION: Despite increase in costs due to longer life DMPs are cost-effective.