The KTx360°-study: a multicenter, multisectoral, multimodal, telemedicine-based follow-up care model to improve care and reduce health-care costs after kidney transplantation in children and adults.

BACKGROUND: Follow-up care after kidney transplantation is performed in transplant centers as well as in local nephrologist's practices in Germany. However, organized integrated care of these different sectors of the German health care system is missing. This organizational deficit as well as non-adherence of kidney recipients and longterm cardiovascular complications are major reasons for an impaired patient and graft survival. METHODS: The KTx360° study is supported by a grant from the Federal Joint Committee of the Federal Republic of Germany. The study will include 448 (39 children) incident patients of all ages with KTx after study start in May 2017 and 963 (83 children) prevalent patients with KTx between 2010 and 2016. The collaboration between transplant centers and nephrologists in private local practices will be supported by internet-based case-files and scheduled virtual visits (patient consultation via video conferencing). At specified points of the care process patients will receive cardiovascular and adherence assessments and respective interventions. Care will be coordinated by an additional case management. The goals of the study will be evaluated by an independent institute using claims data from the statutory health insurances and data collected from patients and their caregivers during study participation. To model longitudinal changes after transplantation and differences in changes and levels of immunosuppresive therapy after transplantation between study participants and historical data as well as data from control patients who do not participate in KTx360°, adjusted regression analyses, such as mixed models with repeated measures, will be used. Relevant confounders will be controlled in all analyses. DISCUSSION: The study aims to prolong patient and graft survival, to reduce avoidable hospitalizations, co-morbidities and health care costs, and to enhance quality of life of patients after kidney transplantation. TRIAL REGISTRATION: ISRCTN29416382 (retrospectively registered on 05.05.2017).

[Implementation of perinatal regionalization: frequency of high-risk deliveries outside of specialized perinatal care centres]. / Zur Regionalisierung der perinatalen Versorgung - Wie häufig sind Fehlplatzierungen von Risikogebärenden?

BACKGROUND: The concentration of high-risk deliveries in specialized perinatal care centres contributes to the reduction of infant mortality and morbidity. This study investigates the frequency of high-risk deliveries in hospitals with inadequate level of perinatal care. METHODS: From the files of a German statutory health insurance we draw a random sample of 3.967 women who gave birth april to june 2002. The women received a questionnaire and were asked to send in their "maternity logbook", a document that every pregnant woman receives and where prenatal visits and births are documented by the obstetricians in standardized form. From the 1,593 responders (response rate 40.2 %) we selected 559 high-risk cases. 83 of these (14.8 %) delivered at a specialized perinatal care centre. The remaining 476 deliveries were subjected to an individual analysis of their data. Based on published guidelines for antenatal transport and on data about the perinatal care facilities of German hospitals the adequacy of the delivery hospital was rated for each case. RESULTS: 2.4 % of the whole sample (38/1,503) were classified as "inadequate hospital of delivery". 17 of these 38 cases were considered as potentially avoidable because significant antepartal risk factors were documented. 5 (25 %) of the 20 highest risk cases (twins < 36 weeks of gestational age, singletons < 32 weeks, infants < 1.500 g) were classified as avoidable referrals to inadequate hospitals. CONCLUSIONS: Regionalization of perinatal care must be enhanced by adequate appreciation of antenatal risk factors and counselling of pregnant women on the choice of place of delivery.

[What kind of information is expected to be provided by medical information services?]. / Welche Informationen erwarten Patienten und Versicherte von medizinischen Informationsdiensten?

OBJECTIVE: The improvement of health-related information services is one major issue in reforming the German health care system to provide more transparency in health care services for patients and persons covered by the German statutory health insurance system. To meet the general need for specific medical information a telephone-based health information service may give individual advice and provide a helpful selection of information. The study aims at users expectations and preferences with regard to health information services. More particularly, users perception concerning the type of health information and the ways of choosing the information were to be explored. METHOD: The study included 160 participants of different ages. Prototypical medical advice conversations were presented to the participants consisting of/identifying the consumer's inquiry, followed by the expert's answering sequence. The answers were based on typical inquiries from medical information providers focussing on treatment methods and illnesses. Health information from these conversations with its special contents were ranked by preference judgements resulting in Thurstone scalings. RESULTS: In terms of different health questions, the participants' judgements showed general preference structures for special health information, independent from any personal attitude towards medical information services. Great emphasis was placed on the medical conversation competence of the service provider, which is evident from recognising the specific needs and selection of information of a caller. Overall such health information was preferred that strengthened the patient's and user's autonomy and ability for decision making. CONCLUSION: Patients and persons covered by German statutory health insurance are characterised as users of information by special preferences. Identifying these preferences permits a reasonable selection of information and individual advice. Therefore, these services provide a major advantage over non-interactive health information services (print media, internet sites).

[Job strain as a risk factor for occupational accidents among hospital nursing staff]. / Psychischer Stress als Risikofaktor für Arbeitsunfälle bei Pflegekräften im Krankenhaus.

In a cross-sectional questionnaire study the influence of psychological job strain and nine other factors on the occurrence of accidents at work were examined. Data were collected by a national survey of nursing personnel in Germany. The sample of this study consists of 874 nurses working in acute care hospitals. Job strain was operationalised according to Karasek's demand-control model and measured by a self-developed questionnaire. 32 % had experienced at least one accident during the 12 months preceding the survey (mostly accidental cuts or needle punctures). No association with accident risk was found for age, sex, professional status (supervising function) and hours of overtime work. The six factors significantly associated with accident risk in univariate analyses were entered into a logistic regression model: high job strain, working in a functional unit (e. g. laboratory), full-time work, less than 3 years of occupation in the present department, having children of less than 3 years of age and being a single parent. In the multivariate analyses high job strain turned out to be the most important risk factor for occupational accidents (odds ratio: 2.4, 95 % C.I.: 1.7-3.3). Significantly elevated risks were found for full-time work, less than 3 years of occupation in the present department and being a single parent (odds ratios between 1.5 and 1.8). Having at least one child of less than 3 years of age was a protective factor (odds ratio 0.5, 95-% C.I.: 0.4-0.8).

Kinetic and spectroscopic characterization of native and metal-substituted beta-lactamase from Aeromonas hydrophila AE036.

Two metal ion binding sites are conserved in metallo-beta-lactamase from Aeromonas hydrophila. The ligands of a first zinc ion bound with picomolar dissociation constant were identified by EXAFS spectroscopy as one Cys, two His and one additional N/O donor. Sulfur-to-metal charge transfer bands are observed for all mono- and di-metal species substituted with Cu(II) or Co(II) due to ligation of the single conserved cysteine residue. Binding of a second metal ion results in non-competitive inhibition which might be explained by an alternative kinetic mechanism. A possible partition of metal ions between the two binding sites is discussed.

Mono- and binuclear Zn2+-beta-lactamase. Role of the conserved cysteine in the catalytic mechanism.

When expressed by pathogenic bacteria, Zn2+-beta-lactamases induce resistance to most beta-lactam antibiotics. A possible strategy to fight these bacteria would be a combined therapy with non-toxic inhibitors of Zn2+-beta-lactamases together with standard antibiotics. For this purpose, it is important to verify that the inhibitor is effective under all clinical conditions. We have investigated the correlation between the number of zinc ions bound to the Zn2+-beta-lactamase from Bacillus cereus and hydrolysis of benzylpenicillin and nitrocefin for the wild type and a mutant where cysteine 168 is replaced by alanine. It is shown that both the mono-Zn2+ (mononuclear) and di-Zn2+ (binuclear) Zn2+-beta-lactamases are catalytically active but with different kinetic properties. The mono-Zn2+-beta-lactamase requires the conserved cysteine residue for hydrolysis of the beta-lactam ring in contrast to the binuclear enzyme where the cysteine residue is not essential. Substrate affinity is not significantly affected by the mutation for the mononuclear enzyme but is decreased for the binuclear enzyme. These results were derived from kinetic studies on two wild types and the mutant enzyme with benzylpenicillin and nitrocefin as substrates. Thus, targeting drug design to modify this residue might represent an efficient strategy, the more so if it also interferes with the formation of the binuclear enzyme.

Structure and orientation of the oxygen-evolving manganese complex of green algae and higher plants investigated by X-ray absorption linear dichroism spectroscopy on oriented photosystem II membrane particles.

X-ray absorption spectroscopy at the Mn K-edge has been performed on multilayers of photosystem II-enriched fragments of the native thylakoid membrane prepared from a higher plant (spinach) and a unicellular green alga (Scenedesmus obliquus). Spectra collected for various angles between the prevailing orientation of the thylakoid membrane normal and the X-ray electric field vector contain information on the atomic structure of the tetranuclear manganese complex of photosystem II (PS II) and its orientation with respect to the membrane normal. The previously used approach for evaluation of the dichroism of extended X-ray absorption fine structure (EXAFS) spectra [George, G. N., et al. (1989) Science 243, 789-791] is modified, and the following results are obtained for PS II in its dark-stable state (S1-state): (1) structure and orientation of the PS II manganese complexes of green algae and higher plants are highly similiar or fully identical; (2) two 2.7-A vectors, which, most likely, connect the Mn nuclei of a planar Mn2(mu-O2) structure, are at an average angle of 80 degrees +/- 10 degrees with respect to the thylakoid normal; (3) the plane of the Mn2(mu-O2) structures is rather in parallel with the thylakoid plane than perpendicular. Structural models for the oxygen-evolving manganese complex and its orientation in the thylakoid membrane are discussed within the context of the presented results.

The iron ligand sphere geometry of mammalian 15-lipoxygenases.

We investigated the geometry of the iron ligand sphere of the native rabbit 15-lipoxygenase (15-LOX) by X-ray absorption spectroscopy using synchrotron radiation. The soybean LOX-1 was used as a reference compound because its iron ligand sphere is well characterized. For structural information the X-ray absorption spectra were evaluated using the Excurve Program (CCLRC Daresbury Laboratory, Warrington, U.K.). From the positions of the absorption edges and from the intensities of the 1s-3d pre-edge transition peaks a six-coordinate ferrous iron was concluded for the rabbit 15-LOX. Evaluation of the extended region of the absorption spectra suggested six nitrogen and/or oxygen atoms as direct iron ligands, and the following binding distances were determined (means+/-S.D.; estimated accuracy is +/-0.001nm for bond distances, on the basis of more than 22 X-ray absorption spectra): 0.213+/-0.001nm, 0.213+/-0. 001 nm, 0.236+/-0.001 nm, 0.293+/-0.001 nm, 0.189+/-0.001 nm and 0. 242+/-0.001. Lyophilization of the LOX altered the binding distances but did not destroy the octahedral iron ligand sphere. For construction of a structural model of the iron ligand sphere the binding distances extracted from the X-ray spectra were assigned to specific amino acids (His-360, -365, -540, -544 and the C-terminal Ile-662) by molecular modelling using the crystal coordinates of the soybean LOX-1 and of a rabbit 15-LOX-inhibitor complex.

[Effectiveness of secondary preventive programs for patients with asthma and rhinitis in the baking industry]. / Effektivität eines Sekundär-Präventionsprogramms für asthmatisch und rhinitisch Erkrankte im Bäckerhandwerk.

Since 1992 the German industrial professional association for the food industry and gastronomy (Berufsgenossenschaft Nahrungsmittel und Gaststätten), which is responsible for statutory accident insurance has been offering a specific patient education programme to bakers suffering from occupationally induced obstructive pulmonary disease or allergic rhino-conjunctivitis, who do not quit their jobs and wish to continue working as bakers. The programme aims at preventing aggravation of the disease 74 male bakers with a mean duration of illness of 10 years on entering the programme were examined between 1 and 5 years (mean: 2.9) after participating in the patient education seminar. For a subpopulation of 55 of these patients spirometric measurements were available for the time before programme entry and at follow-up. Data on time spent at the bakehouse, prevalence of symptoms, frequency of symptoms at the site of working and during leisure hours, sleep disturbances and emergency situations were collected at the follow-up examination both for the time before programme entry and at follow-up, respectively. Direct ratings of the amount of changes in distress caused by the disease and of the quality of life were also obtained. The prevalence of 8 of the 9 most frequently reported symptoms decreased significantly, e.g. dysponoea from 70% to 42% and fear of suffocation from 30% to 3%. Participants reported on highly significant reductions in the frequency of disease-specific complaints during work and outside the working place, sleep disturbances and situations requiring immediate medical intervention. Between 64% and 85% of the patients experienced improvement of distress, physical and work performance, private and family life, and ability for self-management. Lung function did not deteriorate: mean FEV1 was 88% (+/- 23) at first and 90% (+/- 19) at second measurement. These results could not be explained by changes in medication. It is concluded that the programme is effective in reducing symptoms and distress and in improving quality of life in bakers with occupational respiratory disease who voluntarily continue to work as bakers.

[Decreasing violence in the school: study of a cooperative intervention]. / Gewaltverminderung in der Schule: Erprobung einer kooperativen Intervention.

Can physically aggressive behavior among pupils be reduced by some easily applicable interventions? The teaching staffs of four elementary schools were advised (1) to hold regular classroom meetings (on rules of behavior, helping attacked peers etc), (2) to stop acute aggressive behavior and encourage positive behavior, and (3) to change some situational factors (especially during break-time). Preliminary results suggest that a highly committed staff can reduce aggressive behavior by these interventions. Further study is needed, however, as to the contribution of individual measures and the extent and stability of the effects to be obtained.

[Current status and analysis of diagnostic and therapeutic guidelines in the area of chronic obstructive respiratory tract diseases in adulthood]. / Bestandsaufnahme und Analyse von Diagnose- und Therapieleitlinien im Bereich der chronisch obstruktiven Atemwegserkrankungen im Erwachsenenalter.

UNLABELLED: GOAL OF THE INVESTIGATION: It was investigated (1) whether guidelines for the treatment of bronchial asthma and chronic obstructive pulmonary diseases (chronic obstructive bronchitis and lung emphysema) are distributed in Germany, (2) whether they are accepted by general practitioners and physicians for internal medicine without subspecialty, and (3) how much they are used. METHODS: (1) The mostly read medical journals have been screened. (2) 1200 physicians have been questioned with regard to the main criteria of these guidelines. (3) 600 physicians were asked to write a documentation for two patients each with bronchial asthma and chronic obstructive pulmonary disease. 344 of the questionnaires (28.7%) and 544 of the documentations could be analyzed (22.7%). RESULTS: Guidelines for the treatment of bronchial asthma are published in all leading journals. Substantially less references were found for the therapy of chronic obstructive bronchitis. The main concepts of training, diagnosis of the disease's severity, and physical therapy are all known by the practitioners. The training plays a sufficient role in only half of the questioned physicians. The self-measurement of the patient is not every where accepted. The treatment according to a stage by stage pharmacological therapy cannot be seen in one third of the questioned physicians. CONCLUSIONS: Differential diagnosis and therapy are not sufficiently emphasized in the current guidelines. Practitioners should participate in the development of guidelines, to include the aspects of realization.

Mössbauer, electron-paramagnetic-resonance and X-ray-absorption fine-structure studies of the iron environment in recombinant human tyrosine hydroxylase.

Isoforms (1-4) of human tyrosine hydroxylase (TH) have been expressed in Escherichia coli and purified as apoenzymes (metal-free). Apo-human TH binds 1.0 atom Fe(II)/enzyme subunit, and iron binding is associated with an immediate and dramatic (40-fold) increase in specific activity. For X-ray absorption fine structure (XAFS) and electron paramagnetic resonance (EPR) measurements the apoenzyme was reconstituted with 56Fe and for Mössbauer measurements with 57Fe. XAFS measurements at the Fe-K edge of human TH were performed on the native form [Fe(II)-human TH], as well as after addition of stoichiometric amounts of the substrate tetrahydropterin, the inhibitor dopamine and of H2O2. The addition of dopamine or H2O2 oxidizes the ferrous iron of the native human TH to the ferric state. In both redox states the iron is octahedrally coordinated by low-Z backscatterers, thus sulfur coordination can be excluded. From the multiple scattering analysis of the EXAFS region is was surmised that part of the iron coordination is due to (3 +/- 1) imidazols. Addition of tetrahydropterin does not significantly change the iron coordination of the Fe(II) enzyme. The Mössbauer results confirm the valence states and the octahedral coordination of iron as well as the exclusion of sulfur ligation. Both the EPR spectra and the Mössbauer magnetic hyperfine pattern of dopamine- and H2O2-treated native human TH, were analyzed with the spin-Hamiltonian formalism. This analysis provides significantly different features for the two forms of human TH: the ferric iron (S = 5/2) of the H2O2-treated form exhibits a rhombic environment while that of the dopamine-treated form exhibits near-axial symmetry. The specific spectroscopic signature of dopamine-treated human TH, including that of an earlier resonance-Raman study [Michaud-Soret, I., Andersson, K. K., Que, L. Jr & Haavik, J. (1995) Biochemistry 34, 5504-5510] is most likely due to the bidentate binding of dopamine to iron.

Nitric oxide oxidises a ferrous mammalian lipoxygenase to a pre-activated ferric species.

Nitric oxide is known as an inhibitor of soybean lipoxygenase-1. Investigating the interaction of a mammalian 15-lipoxygenase with nitric oxide, we found that this enzyme is also inhibited reversibly when incubated with nitric oxide for a short time period (5 s) under anaerobic conditions. This inhibition may be due to the formation of a dissociable lipoxygenase-nitric oxide complex. With longer incubation periods the ferrous lipoxygenase is oxidised to a ferric form. This oxidation renders the enzyme more susceptible to peroxide activation, causing a time-dependent shortening of the kinetic lag phase.

X-ray absorption spectroscopy study of native and phenylphosphorodiamidate-inhibited Bacillus pasteurii urease.

X-ray absorption spectroscopy (XAS) has been applied to urease from Bacillus pasteurii, a highly ureolytic soil bacterium, with the aim of elucidating the structural details of the nickel-containing active site. The results indicate the presence of octahedrally coordinated Ni2+, in a sphere of six N/O donors at an average distance of 0.203 nm. An average of two histidine residues are bound to nickel. The experimental evidence suggests direct binding of the urease inhibitor phenylphosphorodiamidate to Ni2+. These spectroscopic results are in agreement with previous findings on both plant and microbial ureases, but differ in some respect from the results obtained by X-ray crystallography analysis of Klebsiella aerogenes urease.

EXAFS investigation of the active site of iron superoxide dismutase of Escherichia coli and Propionibacterium shermanii.

The local structure of the iron site in ferric superoxide dismutase from P. shermanii was analyzed by X-ray absorption spectroscopy. The metal-ligand cluster of the enzyme is found to be similar to the crystallographically investigated ferric superoxide dismutase from E. coli. At pH 6.4 the enzyme is five-fold coordinated with three histidines, an aspartate and a water molecule. The average bond lengths between the metal and the histidines are about 2.10 A, between metal and aspartate they are about 1.86 A and between metal and water 1.96 A. With an increase in pH a change in the coordination number from five to six is observed both in pre-edge peak and EXAFS spectra analysis. However, the bond lengths of the ligands do not change dramatically, they are conserved for the aspartate and increase slightly to 2.13 A for the average metal-histidine distance at pH 9.3. The observation of the increase in coordination number is correlated with a decrease in enzymatic activity which occurs in the high pH range. The zinc EXAFS spectra of P. shermanii superoxide dismutase have shown that zinc can be incorporated in the active center instead of the iron.

Changes in the iron coordination sphere of Fe(II) lipoxygenase-1 from soybeans upon binding of linoleate or oleate.

Fe K-edge X-ray absorption spectra of the non-heme iron constituent of lipoxygenase-1 from soybeans were obtained. The spectrum of 2.5 mM Fe(II) lipoxygenase, mixed with 1.2 M linoleate in the absence of O2, was compared to the spectrum of the native (i.e. untreated) enzyme. In the lipoxygenase-linoleate complex, an edge shift to lower energy was observed. This indicated that the iron-ligand distances in this complex are slightly longer than those in the untreated enzyme species. The extended X-ray absorption fine structure spectrum of Fe(II) lipoxygenase, prepared by anaerobic reduction of 2.5 mM Fe(II) lipoxygenase with 1.2 M linoleate, was very similar to the spectrum of the anaerobic lipoxygenase-linoleate complex. We conclude that the conformational differences between the iron coordination spheres of native and cycled Fe(II) lipoxygenase must be ascribed to the presence of linoleate, and not to changes in the enzyme that occur only after one cycle of oxidation and reduction. Furthermore, spectra of 2.5 mM Fe(II) lipoxygenase mixed with 1.2 M oleate, either in the absence or in the presence of O2, were also identical to the spectrum of the Fe(II) lipoxygenase-linoleate complex. This finding is in agreement with our observation that oleate is a competitive inhibitor of the lipoxygenase reaction. Moreover, the similarity of the lipoxygenase-oleate complexes in the presence and absence of O2 excludes the possibility that O2 binding to the iron cofactor is induced upon binding of a fatty acid to lipoxygenase.