[How complete is the Germany-wide standardised medication list ("Bundeseinheitlicher Medikationsplan")? An analysis at hospital admission.] / Wie vollständig ist der Bundeseinheitliche Medikationsplan? Eine Analyse bei Krankenhausaufnahme.

BACKGROUND: At inpatient admission, the timeliness and completeness of the Germany-wide standardised medication list ("Bundeseinheitlicher Medikationsplan") often seems inappropriate. It is also unclear which characteristics of the lists increase the probability of discrepancies. METHODS: A total of 100 medication lists of elective patients of a surgical clinic were retrospectively evaluated with regard to potential discrepancies compared to the standardised medication reconciliation. The discprepancies were assigned to 7 categories: drug taken is missing on the list, drug on the list is no longer taken, strength or dosage is missing at the list or is incorrect, or the documented dosage form is different. Advice on patient safety, involved drugs and dosage forms were also recorded. Multivariate analyses were used to investigate the influence of the timeliness, number of drugs and issuing medical specialty of the lists on the type and number of discrepancies. RESULTS: Compared to the medication reconciliation, 78 % (78/100) of the lists showed discrepancies. A total of 226 deviations (2.3 ±â€Š0.6 deviations/list) were documented. Most often, a drug was missing from the list (n = 103). Of all recommendations, 64 % (83/177) concerned the perioperative management of anticoagulants (n = 55) and antidiabetics (n = 28), corresponding to 62 % (62/100) of the lists. In the multivariate analysis, only the risk of incorrect information on strength and dosage increased significantly with the age of the lists (p = 0.047) and was more than twice as high when the list was more than one month old. CONCLUSIONS: The timeliness, completeness and aspects of patient safety must be comprehensively validated. Medication lists that are older than 1 month should be checked particularly critically with regard to information on strength and dosage and the plan should be updated accordingly at regular intervals.

Structure and Chemistry of SeFx(CN)4-x Compounds.

Several new SeF2(CN)2-donor complexes with N or O based donor molecules are reported. Due to orbital overlap effects 12-crown-4 (1,4,7,10-tetraoxacyclododecane) shows unsymmetric ether oxygen coordination. Solvent coordination (secondary bonding interactions, SBI) in SeFx(CN)4-x compounds is weak and does not influence decomposition pathways (neutral and anionic). Barriers for decomposition are relatively high in SeF2(CN)2 but decrease significantly in compounds with higher cyanide content. In the presence of fluoride ions, facile substitution pathways exist; however, reductive elimination is also favored. In the absence of fluoride ions decomposition barriers are higher, but so are substitution barriers (σ-metathesis). Therefore, successful isolation of Se(CN)4 appears to be significantly hampered. In addition, previously unknown trifluoromethyliminoseleniumdifluoride was cleanly synthesized utilizing the instability of SeF(CN)3 toward reductive FCN elimination (preferred over the thermodynamically favored NCCN elimination) and subsequent FCN incorporation to SeF4 through double F-migration.

Influenza vaccine response profiles are affected by vaccine preparation and preexisting immunity, but not HIV infection.

Vaccines dramatically reduce infection-related morbidity and mortality. Determining factors that modulate the host response is key to rational vaccine design and demands unsupervised analysis. To longitudinally resolve influenza-specific humoral immune response dynamics we constructed vaccine response profiles of influenza A- and B-specific IgM and IgG levels from 42 healthy and 31 HIV infected influenza-vaccinated individuals. Pre-vaccination antibody levels and levels at 3 predefined time points after vaccination were included in each profile. We performed hierarchical clustering on these profiles to study the extent to which HIV infection associated immune dysfunction, adaptive immune factors (pre-existing influenza-specific antibodies, T cell responses), an innate immune factor (Mannose Binding Lectin, MBL), demographic characteristics (gender, age), or the vaccine preparation (split vs. virosomal) impacted the immune response to influenza vaccination. Hierarchical clustering associated vaccine preparation and pre-existing IgG levels with the profiles of healthy individuals. In contrast to previous in vitro and animal data, MBL levels had no impact on the adaptive vaccine response. Importantly, while HIV infected subjects with low CD4 T cell counts showed a reduced magnitude of their vaccine response, their response profiles were indistinguishable from those of healthy controls, suggesting quantitative but not qualitative deficits. Unsupervised profile-based analysis ranks factors impacting the vaccine-response by relative importance, with substantial implications for comparing, designing and improving vaccine preparations and strategies. Profile similarity between HIV infected and HIV negative individuals suggests merely quantitative differences in the vaccine response in these individuals, offering a rationale for boosting strategies in the HIV infected population.

Preserved antigen-specific immune response in patients with multiple sclerosis responding to IFNß-therapy.

BACKGROUND: Interferon-beta (IFNß) regulates the expression of a complex set of pro- as well as anti-inflammatory genes. In cohorts of MS patients unstratified for therapeutic response to IFNß, normal vaccine-specific immune responses have been observed. Data capturing antigen-specific immune responses in cohorts of subjects defined by response to IFNß-therapy are not available. OBJECTIVE: To assess antigen-specific immune responses in a cohort of MS patients responding clinically and radiologically to IFNß. METHODS: In 26 MS patients, clinical and MRI disease activity were assessed before and under treatment with IFNß. Humoral and cellular immune response to influenza vaccine was prospectively characterized in these individuals, and 33 healthy controls by influenza-specific Enzyme-Linked Immunosorbent Assay (ELISA) and Enzyme Linked Immuno Spot Technique (ELISPOT). RESULTS: Related to pre-treatment disease activity, IFNß reduced clinical and radiological MS disease-activity. Following influenza vaccination, frequencies of influenza-specific T cells and concentrations of anti-influenza A and B IgM and IgG increased comparably in MS-patients and in healthy controls. CONCLUSIONS: By showing in a cohort of MS-patients responding to IFNß vaccine-specific immune responses comparable to controls, this study indicates that antigen-specific immune responses can be preserved under successful IFNß-therapy.

Development and evaluation of a computerised clinical decision support system for switching drugs at the interface between primary and tertiary care.

BACKGROUND: Upon admission to a hospital patients' medications are frequently switched to alternative drugs compiled in so called hospital drug formularies. This substitution process is a laborious and error-prone task which should be supported by sophisticated electronic tools. We developed a computerised decision support system and evaluated benefit and potential harm associated with its use. METHODS: Based on a multi-step algorithm we identified drug classes suitable for exchange, defined conversion factors for therapeutic interchange, built a web-based decision support system, and implemented it into the computerised physician order entry of a large university hospital. For evaluation we compared medications manually switched by clinical pharmacists with the results of automated switching by the newly developed computer system and optimised the system in an iterative process. Thereafter the final system was tested in an independent set of prescriptions. RESULTS: After iterative optimisation of the logical framework the tool was able to switch drugs to pharmaceutical equivalents and alternatives; in addition, it contained 21 different drug classes for therapeutic substitution. In this final version it switched 91.6% of 202 documented medication consultations (containing 1,333 drugs) automatically, leaving 8.4% for manual processing by clinical professionals. No incorrect drug switches were found. CONCLUSION: A large majority (>90%) of drug switches performed at the interface between primary and tertiary care can be handled automatically using electronic decision support systems, indicating that medication errors and workload of healthcare professionals can be considerably reduced.

Antigen-specific adaptive immune responses in fingolimod-treated multiple sclerosis patients.

T cells exit secondary lymphoid organs along a sphingosine1-phosphate (S1P) gradient and, accordingly, are reduced in blood upon fingolimod-mediated S1P-receptor (S1PR)-blockade. Serving as a model of adaptive immunity, we characterized cellular and humoral immune responses to influenza vaccine in fingolimod-treated patients with multiple sclerosis (MS) and in untreated healthy controls. Although the mode of action of fingolimod might predict reduced immunity, vaccine-triggered T cells accumulated normally in blood despite efficient S1PR-blockade. Concentrations of anti-influenza A/B immunoglobulin (Ig)M and IgG also increased similarly in both groups. These results indicate that fingolimod-treated individuals can mount vaccine-specific adaptive immune responses comparable to healthy controls.

Virosomal influenza-vaccine induced immunity in HIV-infected individuals with high versus low CD4+ T-cell counts: clues towards a rational vaccination strategy.

In a prospective influenza-vaccination trial we show that HIV-infected individuals with CD4 T-cell counts less than 350 microl were distinct from HIV-infected individuals with more than 350 CD4 T-cell counts/microl, and from HIV-negative individuals, in that an influenza-specific immunoglobulin M-response was absent and expansion of interferon-gamma-secreting CD4 T cells was impaired. By contrast, immunoglobulin G-responses were induced in all study groups. These data suggest that establishing broad influenza-specific (immunoglobulin G) B-cell memory prior to severe immunodeficiency is important.