[Caesarean section in german hospitals: validity of hospital quality report data for monitoring C-section rates]. / Kaiserschnitte in deutschen Krankenhäusern: Wie zuverlässig sind Routinedaten aus dem strukturierten Qualitätsbericht für die Bestimmung der Kaiserschnittraten?

OBJECTIVE: It is not known if "hospital quality reports" (HQR) document Caesarean (C-) section rates at the hospital level accurately enough for use as a reliable data source when it comes to explaining regional variations of C-sections in Germany by factors at the hospital level. We aimed to answer this question using HQR from hospitals in Baden-Württemberg as data source. METHOD: Diagnostic and procedure codes from HQR for the year 2008 (HQRdata), were used to calculate numbers of births, numbers of C-sections, and rates of births by C-section (CSR) for 94 of 97 hospitals in Baden-Württemberg. These numbers were compared to internal hospital (IH) data delivered upon request by 80 of 97 hospitals and stemming from vital statistics, birth registry forms, or external quality assurance datasets. RESULTS: There was no difference in the number of births between HQR data and IH data, but the number of C-sections and the CSR differed significantly (p<0.05; Wilcoxon rank sum test). CSR calculated using HQR data was 4.9 ± 17.9% higher than CSR from IH data (absolute difference 1.5 ± 5.8%). The correlation between the 2 data sources was moderate (r=0.73). Only 55% of the variance in IH data-based CSR was explained by HQR data. The proportion between highest and lowest CSR in hospitals in Baden-Württemberg was 4.9 for HQR data and 3.6 for IH data. CONCLUSION: There are significant and relevant differences between C-section rates based on ei-ther HQR or IH data. This questions routine data from HQR for 2008 as a reliable data source for research work.

[Perinatal centres in the state of Baden-Württemberg: effects of minimum volume standards and quality assessments by the Medical Service of Statutory Health Insurance (MDK)]. / Perinatalzentren in Baden-Württemberg: Auswirkungen von Mindestmengen und Qualitätsprüfungen durch den Medizinischen Dienst der Krankenversicherung (MDK).

BACKGROUND: In the year 2009 the Federal Joint Committee (G-BA) obliged neonatal units in Germany to publish yearly data on the number of preterm infants treated and their outcome in the internet. At the same time annual minimum volumes were introduced for each level of perinatal care. The exact numbers of compulsory minimum volumes are heavily discussed both scientifically and politically. METHODS: 28 perinatal centres (PNC) in the state of Baden-Württemberg published data on mortality and short-term morbidity of preterm infants with a birth weight (BW) <1,500 g admitted in the year 2008 (n=1,141). These data were analysed on the background of quality assessments of structures and processes in all hospitals performed by the Medical Service of Statutory Health Insurance (MDK). RESULTS: By the end of 2008, 8 PNC had fulfilled the quality criteria of the G-BA nearly completely and reached a numerical benchmarking value of more than 300 of 465 maximally achievable points. Introducing annual minimum volumes of 36 preterm infants with a BW <1,250 g would lead to a concentration of perinatal care in 7 PNC and minimum volumes of 50 preterm infants with a BW <1,500 g per year in 8 such centres. CONCLUSION: Further centralisation of clinical care for low birth-weight preterm infants in a limited number of PNC in the state of Baden-Württemberg would be economically reasonable and could be achieved either by the introduction of higher minimum volume standards or a stringent interpretation of quality criteria of the G-BA. Based on self-reported data of the PNC currently available in the Internet it is not possible to predict the effect of such a centralisation process on patient outcome.

Constitutive activation and accelerated maturation of peripheral blood T cells in healthy adults in Burkina Faso compared to Germany: the case of malaria?

OBJECTIVE: It is not exactly known how frequent exposure to Plasmodium falciparum shapes the peripheral blood T-cell population in healthy West Africans. METHODS: The frequency of peripheral blood CD4(+) lymphocytes responding to Plasmodium falciparum merozoite surface protein 1 (PfMSP-1) by production of interferon-gamma (IFN-γ), interleukin-2 (IL-2) or tumor necrosis factor-alpha (TNF-α) was determined using a commercially available flow cytometric activation assay (FastImmune) in 17 healthy adults in Nouna, Burkina Faso. T-cell activation and maturation in peripheral blood of healthy adults in Burkina Faso (n=40) and Germany (n=20) were compared using immunophenotyping and three-colour flow cytometry. RESULTS: Significant numbers of PfMSP-1 -specific CD4(+) lymphocytes producing IFN-γ, IL-2 and/or TNF-α were detected in 14 healthy adults in Nouna. Cytokine profiles showed predominant production of IFN-γ and TNF-α. Compared to Germans, Burkinabé showed markedly lower proportions of CCR7+ CD45RA+ naive CD4(+) cells and slightly higher frequencies of CD95(+)CD4(+) T-cells and of CD38(+) CD8(+) T-cells. The median antibody-binding capacity of CD95(dim) CD4(+) T-cells in Burkinabé was more than twice the value observed in Germans (263 vs. 108 binding sites per cell, p<0.0001). CONCLUSIONS: We hypothesize that an IFN-γ-induced increase in the expression level of CD95 on CD4(+) lymphocytes may lower the activation threshold of resting naive CD4(+) T-cells in healthy adults living in Burkina Faso. Bystander activation of these cells deserves further study as a molecular mechanism linking strong IFN-γ responses against Plasmodium falciparum to decreased susceptibility to parasitemia observed in specific ethnic groups in West Africa.

HLA class I antibodies provoke graft arteriosclerosis in human arteries transplanted into SCID/beige mice.

Antibodies toward HLA class I and/or MICA are commonly observed in transplanted patients suffering from allograft arteriosclerosis, also called chronic vascular rejection (CVR). The relative importance of cellular versus humoral alloreactivity for CVR is still disputed. We demonstrate that antibodies toward HLA class I provoke lesions typical for CVR in human arteries in vivo in the absence of cellular immunity. To show this, we grafted segments of human mesenteric arteries from 8 deceased organ donors into 36 immunodeficient SCID/beige mice in the infrarenal aortic position. Three mice died postoperatively. The remaining 33 mice received weekly i.v. injections of either a monoclonal antibody toward HLA class I, toward MICA or an irrelevant monoclonal antibody. At sacrifice after 6 weeks, mice receiving the HLA antibody showed a significant neointimal thickening in the grafted artery due to smooth muscle cell (SMC) proliferation while control mice receiving anti-MICA or irrelevant antibody showed little or no thickening. Whereas antibodies toward HLA class I were mitogenic to SMC in vitro, those directed toward MICA did not have any effect. Humoral alloreactivity toward HLA may thus play a causal role for the development of CVR and this opens new possibilities for the treatment of CVR.

FTY720 Inhibits Tumor Necrosis Factor-alpha-Induced Proliferation and Extracellular Signal-Regulated Kinase Phosphorylation of Human Smooth Muscle Cells.

We investigated the effects of the sphingolipid FTY720 on tumor necrosis factor-alpha (TNF-alpha)-induced proliferation and signal transduction in human smooth muscle cells (SMC). We showed that clinically relevant concentrations of FTY720 inhibited TNF-alpha-induced SMC proliferation and extracellular signal-regulated kinase (ERK) phosphorylation. We concluded that FTY720 may be a useful drug to inhibit chronic vascular rejection.

T-cell function in maintenance renal transplant patients receiving mycophenolate mofetil and steroids with or without tacrolimus.

Nephrotoxicity-sparing protocols, using mycophenolate mofetil (MMF) and steroids without calcineurin inhibitors (CNIs) or mammalian target rapamycin (mTOR), could be used to treat maintenance renal transplant patients. However, the risk for acute rejection seems to be high. The aim of this pharmacodynamic study was to analyze T-cell function, T-cell activation, and T-cell proliferation among patients receiving MMF and steroids (n = 15) compared with patients receiving immunosuppression with CNI-based therapy including tacrolimus, MMF, and steroids. Our data suggested that among stable maintenance patients, dual therapy with MMF and steroids might provide a similar reduction in T-cell proliferation and T-cell activation as that observed among patients on standard immunosuppressive therapy. As expected, intralymphocytic interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) expressions were higher in patients not receiving CNIs.

Effect of FTY720 on apoptosis of smooth muscle cells.

BACKGROUND: Hyperproliferation of smooth muscle cells (SMCs) plays a key role in allograft arteriosclerosis. This prompted us to investigate the effect of the novel immune modulator and synthetic sphingolipid FTY720 on apoptosis of SMCs. METHODS: Rabbit SMC cultures were treated with FTY720 and apoptosis and necrosis were detected by fluorescence microscopy. RESULTS: We investigated dose- and time-dependent effects of FTY720 and found that clinically relevant low doses of FTY720 (<1 micromol/L) did not induce apoptosis, whereas 10 micromol/L FTY720 induced apoptosis after 48 hours incubation. CONCLUSION: At doses of FTY720 used in clinics for treatment of renal allografts and multiple sclerosis. FTY720 did not induce SMC apoptosis.

Immunohematological reference values for healthy adults in Burkina Faso.

Reference ranges for peripheral blood lymphocyte subsets were generated for 186 healthy adults in Burkina Faso using single-platform flow cytometry. CD4(+) T-cell counts ranged from 631 to 1,696 cells microl(-1); they were lower in males (n = 97) than in females (n = 89), whereas natural killer cell counts were higher.

Evaluation of a simplified dual-platform flow cytometric method for measurement of lymphocyte subsets and T-cell maturation phenotypes in the population of Nouna, Burkina Faso.

In the context of a larger clinical study in Nouna, Burkina Faso, we evaluated a simplified dual-platform (DP) flow cytometric (FCM) method that allows the determination of major lymphocyte subsets in a single test tube. We compared the phenotyping of lymphocytes with DP FCM and simultaneous measurements with standard single-platform (SP) FCM for samples from 177 individuals. Analysis of the comparative measurements revealed that DP FCM systematically underestimates the proportion of NK cells, overestimates the percentage of CD3(+) CD8(+) lymphocytes, and yields proportions of B cells and CD4(+) T cells comparable with the results from SP FCM. Bland-Altman analysis showed a low bias between both methods and an acceptable precision for percent values of CD4(+) T cells (bias +/- precision, -1% +/- 6%) and CD8(+) T cells (-3% +/- 6%). The absolute cell numbers of all lymphocyte subpopulations, however, were systematically biased towards lower values being obtained by DP FCM. Reference values for the distribution of T-cell maturation phenotypes in 177 healthy adults were calculated using DP FCM. The mean +/- standard deviation (SD) CD4(+)-to-CD8(+) T-cell ratio was 1.61 +/- 0.61, the mean percentage +/- SD of CD4(+) T cells was 42% +/- 7%, and that of CD8(+) T cells 29% +/- 7%. Among CD4(+) lymphocytes, 28% +/- 7% were classified as central memory (CD45RA(low) CCR7(+)), 22% +/- 10% as naïve (CD45RA(high) CCR7(+)), 45% +/- 12% as effector memory (CD45RA(low) CCR7(-)); and 5% +/- 3% as terminally differentiated effector memory expressing CD45RA (CD45RA(high) CCR7(-)). Among CD8(bright) lymphocytes, 3% +/- 2% had a central memory phenotype, 27% +/- 13% were naïve, 37% +/- 13% had an effector memory phenotype, and 34% +/- 12% were terminally differentiated effector memory cells expressing CD45RA.

Effect of mycophenolate mofetil monotherapy on T-cell functions and inosine monophosphate dehydrogenase activity in patients undergoing a kidney transplantation.

The aim of this study was to assess the effects of 1 g of mycophenolate mofetil (MMF) on T-cell function and inosine monophosphate dehydrogenase (IMPDH) activity among patients undergoing kidney transplantation. Five patients undergoing renal transplantation from a living donor were enrolled in this study. Compared to baseline (before MMF intake), CD25 and CD71 expression were significantly decreased during the first hour following MMF intake. T-cell proliferation and IMPDH activity also decreased dramatically. Thereafter, all biomarker levels increased over time. At 4 hours, CD25 and CD71 levels, as well as IMPDH activity, returned to almost baseline values, whereas T-cell proliferation remained below baseline. Intracytoplasmic IL-2 expression remained unchanged after MMF ingestions. In conclusion, administration of 1 g of MMF was associated with a transient decrease in CD25 expression in addition to a temporary dramatic decrease in both T-cell proliferation and IMPDH activity.

[Neonatal septicemia in the G-DRG system]. / Die Neugeborenensepsis in DRG-System.

INTRODUCTION: The introduction of Diagnosis Related Groups in Germany (G-DRG) has brought forward the obligation for physicians to take into account an intricate system of medical, economical and legal implementations. Mistakes in the process of encoding the principal diagnosis or procedures may have financial consequences. Problems to determine the correct ICD-code will be most prominent for diseases with poorly defined or even inconsistent diagnostic criteria as is the case for neonatal septicemia. We decided to evaluate whether the introduction of G-DRG resulted in a change of frequency of the diagnosis "neonatal septicemia". METHODS: We analysed data derived from the quality assurance program "Neonatalerhebung" in the state of Baden-Württemberg during the years of 2001 through 2004, i. e., 2 years before and 2 years during the introduction of G-DRG. During this period an annual number of 12,316 up to 13,172 newborns were admitted to the participating hospitals. RESULTS: The mean number of diagnoses per patient increased from 2.2 to 3.8. The frequency of the diagnosis of septicemia remained constant. The percentage of newborns receiving antibiotic therapy did not change. The ratio of cases with "septicemia yes" over "antibiotics yes" did not change. Although it is difficult to determine the diagnosis of neonatal septicemia and in spite of the economic implications of this diagnosis, no change in the frequency of this diagnosis occurred during the introduction of DRG. CONCLUSIONS: Assuming that the participating hospitals used an identical database for the quality assurance program "Neonatalerhebung" and for accounting, we conclude that the DRG system is stable with respect to neonatal septicemia.

[Quality assurance of outpatient nursing services in Baden-Württemberg -- overall view of 6 years of a total survey by the Medical Services of the Statutory Health Insurance (MDK)]. / Qualitätsprüfungen ambulanter Pflegedienste in Baden-Württemberg - Uberblick über die Erfahrungen aus 6 Jahren flächendeckender Untersuchungen durch den MDK.

During the years 1997 to 2003 the medical services of the statutory health insurance in the German Federal State of Baden-Württemberg carried out a total survey regarding structure, process and outcome with regard to the quality of care of outpatients in the German long-term care insurance system. This survey provides information on the development of the quality of care. All outpatient nursing services licensed by the statutory long-term care insurance funds in Baden-Württemberg (n (1997 - 2000) = 863; n (2000 - 2003) = 779) were subjected to a uniform assessment based on a consented concept applied in all German Federal States. Our results demonstrate a tendency to fewer but larger nursing services providing care for an increasing number of patients. Qualification of head nurses and of caregiving staff in general has significantly improved. Information for the patient/consumer on the conditions of contracts which have to be made between a nursing service and the patient is still deficient in more than 20 % of cases. Adherence to proper procedures in the process of nursing has improved, especially with respect to taking a complete medical/nursing history and defining the individual resources of a patient and aims for therapy/nursing. However, only in (1/3) of the cases could we find a documentation of continuous adaptation of the planning of therapy. Efforts of in-house quality management and internal quality assurance by the outpatient nursing services have improved. Regarding the outcome of nursing there has been a decrease in the provision of stimulating care from 87 % of cases to 75 %. The majority of patients of outpatient nursing services do not receive benefits of the long-term care insurance system but of the statutory health insurance. This fact underlines the importance of a general conceptual framework for internal and external quality assurance.

[Quality indicators for ambulatory health education programme for overweight and obese children and adolescents]. / Qualitätskriterien für ambulante Schulungsprogramme für übergewichtige und adipöse Kinder und Jugendliche.

BACKGROUND: In Germany, 9 to 12 % of all children between five and seven years of age have been shown to be overweight at school entry; 2.5 to 3.5 % of them are obese. Therapeutic intervention for obese children and adolescents is considered to be indicated especially in cases where an increased body mass index (BMI) is accompanied by a disease the effective treatment of which requires weight loss. Furthermore, the child and its family must be willing to actively change their habits. OBJECTIVE: A multitude of health care providers have begun to offer multidisciplinary group programme for prevention and treatment of obesity to affected individuals and their families. The Medical Service of the Statutory Health Insurance (MDK) has therefore developed a list of quality and assessment criteria for such programme. METHODS: A systematic search for information in international and national publications was performed using standard methodology of evidence-based medicine. Data were extracted and assessed according to pre-defined criteria taking into consideration previously published clinical guidelines and opinions of expert panels. RESULTS: Nearly all available studies were of low internal validity and mostly of poor methodological quality. Therefore, no binding recommendations for the design of health education programme for overweight and obese children and adolescents can be given. Potentially successful intervention should combine the following 4 modules: nutrition, physical activity, change of eating habits, physical activity habits and life style using methods of behavioural therapy, and involvement of parents. Such combinations may have the potential to reduce or stabilise the BMI at least during a defined period of time. In younger children, the beneficial effect will be more pronounced if the parents are actively involved. CONCLUSION: Up to now informative studies have not reliably shown that the effect of ambulatory health education programmes for overweight and obese children and adolescents and their parents may last for more than one or two years. Therefore, a controlled clinical trial determining the long-term effectiveness of such programme is imperative. The decision whether a defined programmes should be included in such a study could be taken on the basis of the quality indicators and assessment criteria described here.

Cyclosporin C2hour monitoring after renal transplantation.

Therapeutic drug monitoring of cyclosporin A (CsA) is essential because of its variable pharmacokinetics in individual patients and its narrow therapeutic window. In the past, standard trough level (C0) monitoring has been used, and although this method is currently the routine strategy, it has been shown that a single blood concentration measurement 2 hours after CsA administration (C2hour) is a significantly more accurate predictor of drug exposure and clinical events than trough concentrations. The CsA absorption profiling, in particular the measurement of C2hour, is a much more sensitive approach to assessing the pharmacokinetics and predicting the clinical effect in the individual patient. However, there are limited prospective data available examining the risks and benefits of C2hour monitoring in renal transplant recipients. Most studies focus on the early post-transplant phase, but there is little experience with C2hour monitoring in maintenance patients. Our experience in 127 stable long-term renal allograft recipients suggests that the therapeutic window for C2hour levels in patients during maintenance is lower than previously anticipated. Repeat determinations of both C0 and C2hour levels in 46 patients to determine precision of C2hour monitoring showed a high intrapatient variability. We observed only a slightly better coefficient of variation for C2hour than for C0 in repeat determinations. This suggests that drug monitoring using C2hour levels in transplant patients may provide a more accurate and reliable measure of drug exposure in the individual patient. However, CsA absorption showed only a weak correlation with dose during repeated measurements, suggesting high variability in absorption in these stable patients. We conclude that an adequate C2hour level soon after transplantation is associated with a reduced risk of acute rejection in adult renal transplant recipients. It is important to identify slow and poor absorbers in the initial phase after transplantation in order to avoid inappropriate increases in CsA dose. In maintenance patients, C2hour values between 500 and 600 ng/ml are effective and safe for providing effective rejection prophylaxis. Although mean C2hour levels do not seem to identify patients at risk of rejection, they may help to identify excessive immunosuppression and to improve long-term survival by reducing CsA toxicity.

Pharmacodynamics of FTY720, the first member of a new class of immune-modulating therapeutics in transplantation medicine.

FTY is a novel immunomodulator currently undergoing clinical investigation and has the potential of improving immunosuppressive therapy after organ transplantation. Previous experimental studies in animals have shown that FTY has a unique mechanism of action. We have studied the pharmacodynamic effects of FTY in stable renal allograft recipients taking part in a phase I clinical trial. As in various animal models including non-human primates, a single oral dose of FTY (0.25 - 3.5 mg) significantly reduced peripheral lymphocyte count by 30 - 70%. The peripheral lymphocyte count returned to baseline within 24 hours. Only in those patients treated with the highest dose of FTY (3.5 mg), did peripheral lymphopenia persist for more than 96 hours. FTY reduced all lymphocyte subsets, T cells more than B cells and CD4+ cells more than CD8+ cells. The reduction in CD3+CD62L+ cell counts was more pronounced, whereas CD3+CCR5+ cell counts were less affected in comparison to the total number of CD3+ lymphocytes. We found only slightly increased apoptosis rates (< 5%) in peripheral lymphocytes, and this change does not explain the marked reduction in lymphocyte count. In cultured human lymphocytes only suprapharmacological doses of 10 microM FTY induced apoptosis (20.6 +/- 2.8%) after a 4-h incubation. More important, clinically relevant doses of 0.1 microM FTY increased lymphocyte mobility 2-fold. No effect of FTY on anti-CD3mAb-stimulated lymphocyte proliferation was detected and there was no change in phagocytosis rates in whole-blood cultures incubated with FTY. Further studies are necessary to investigate the mechanism of action of FTY in detail.