Ulrike Klein

Central venous catheter-related infections in hematology and oncology

Catheter-related infections (CRI) cause considerable morbidity in hospitalized patients. The incidence does not seem to be higher in neutropenic patients than in nonneutropenic patients. Gram-positive bacteria (coagulase-negative staphylococci, Staphylococcus aureus) are the pathogens most frequently cultured, followed by Candida species. Positive blood cultures are the cornerstone in the diagnosis of CRIs, while local signs of infection are not necessarily present. Blood cultures should be taken from peripheral blood and from the venous catheter. A shorter time to positivity of catheter blood cultures as compared with peripheral blood cultures supports the diagnosis of a CRI. In many cases, a definite diagnosis requires catheter removal and microbiological analysis. The role plate method with semiquantitative cultures has been established as standard in most laboratories. Antimicrobial treatment of CRI should be directed by the in vitro susceptibility of the isolated pathogen. Primary removal of the catheter is mandatory in S. aureus and Candida infections, as well as in case of tunnel or pocket infections. Future studies will elucidate whether the rate of CRI in neutropenic patients may be reduced by catheters impregnated with antimicrobial agents.

Chromosomal aberrations +1q21 and del(17p13) predict survival in patients with recurrent multiple myeloma treated with lenalidomide and dexamethasone

In the era of novel agents such as lenalidomide and bortezomib, risk stratification by chromosomal abnormalities may enable a more rational selection of therapeutic approaches in patients with multiple myeloma (MM).

Long-term outcome of nonmyeloablative allogeneic transplantation in patients with high-risk multiple myeloma

Summary:Conventional treatment or autologous transplantation has not been able to achieve long-term remission in patients with multiple myeloma (MM). Nonmyeloablative allogeneic transplantation might offer an option for cure without the high mortality associated with conventional conditioning. Here we present a retrospective analysis of patients with high-risk MM treated with nonmyeloablative allogeneic transplantation. In all, 52 patients with relapsed MM or high-risk features at diagnosis received 2 Gy TBI alone (n=3) or with fludarabine (n=49) as conditioning. Patients were heavily pretreated with a median of eight cycles of conventional chemotherapy and one or more autologous transplants for all but one patient. Regimen-related toxicity was low. Acute graft-versus-host disease II–IV occurred in 37% of patients, and 70% experienced chronic graft-versus-host disease (cGvHD). Median follow-up was 567 days, and transplant-related mortality was 17% in total. Estimated progression-free and overall survival at 18 months was 29.4 and 41.1%, respectively. Patients with cGvHD had a significantly higher progression-free survival, as did patients with up to eight cycles of pretreatment chemotherapy vs those with nine or more. In this highly pretreated patient group, disease control was unsatisfactory and our results suggest that a potential strategy might be to perform allogeneic transplant earlier in the course of the disease.

What, if all alerts were specific – Estimating the potential impact on drug interaction alert burden

PURPOSE Clinical decision support systems (CDSS) may potentially improve prescribing quality, but are subject to poor user acceptance. Reasons for alert overriding have been identified and counterstrategies have been suggested; however, poor alert specificity, a prominent reason of alert overriding, has not been well addressed. This paper aims at structuring modulators that determine alert specificity and estimating their quantitative impact on alert burden. METHODS We developed and summarized optimizing strategies to guarantee the specificity of alerts and applied them to a set of 100 critical and frequent drug interaction (DDI) alerts. Hence, DDI alerts were classified as dynamic, i.e. potentially sensitive to prescription-, co-medication-, or patient-related factors that would change alert severity or render the alert inappropriate compared to static, i.e. always applicable alerts not modulated by cofactors. RESULTS Within the subset of 100 critical DDI alerts, only 10 alerts were considered as static and for 7 alerts, relevant factors are not generally available in todays patient charts or their consideration would not impact alert severity. The vast majority, i.e. 83 alerts, might require a decrease in alert severity due to factors related to the prescription (N=13), the co-medication (N=11), individual patient data (N=36), or combinations of them (N=23). Patient-related factors consisted mainly of three lab values, i.e. renal function, potassium, and therapeutic drug monitoring results. CONCLUSION This paper outlines how promising the refinement of knowledge bases is in order to increase specificity and decrease alert burden and suggests how to structure knowledge bases to refine DDI alerting.

Lack of CD56 expression on myeloma cells is not a marker for poor prognosis in patients treated by high-dose chemotherapy and is associated with translocation t(11;14).

Lack of CD56 expression was reported to be associated with a poor prognosis in multiple myeloma (MM) patients treated with conventional chemotherapy. Aim of our retrospective study was to analyse whether CD56 expression on MM cells reveals as a prognostic factor in patients treated with high-dose chemotherapy. MM cells of 99 patients prior to treatment with high-dose chemotherapy were analysed for CD56 expression by flow cytometry. Multivariable analysis of event-free survival in these patients showed no statistically significant difference between the CD56− (n=28) and the CD56+ (n=71) group. The lack of CD56 expression on MM cells of these patients correlated significantly with the presence of translocation (11;14) (t(11;14)) (estimated correlation coefficient=0.655 95%, confidence interval (0.481; 0.779)). In summary, our results indicate that lack of CD56 expression on MM cells is not a prognostic marker in patients treated with high-dose chemotherapy, but is associated with t(11;14).

A web-based system for clinical decision support and knowledge maintenance for deterioration monitoring of hemato-oncological patients

We introduce a web-based clinical decision support system (CDSS) and knowledge maintenance based on rules and a set covering method focusing on the problem of detecting serious comorbidities in hemato-oncological patients who are at high risk of developing serious infections and life threatening complications. We experienced that diagnostic problems which are characterized by fuzzy, uncertain knowledge and overlapping signs, still reveal some kind of patterns that can be transferred into a computer-based decision model. We applied a multi-stage evaluation process to assess the systems diagnostic performance. Depending on how system behavior was compared to presumably correct judgment of a case the correctness rate for closed cases with all data available varied between 58% and 71%, the overall rate after critical review was 84%. However, the real time behavior of our approach which data becoming available as time passes still has to be evaluated and observational studies need to be conducted.

Development of a standardized knowledge base to generate individualized medication plans automatically with drug administration recommendations

We aimed to develop a generic knowledge base with drug administration recommendations which allows the generation of a dynamic and comprehensive medication plan and to evaluate its comprehensibility and potential benefit in a qualitative pilot study with patients and physicians.

Management of Multiple Myeloma and Myelodysplastic Syndrome: Focus on Lenalidomide

Lenalidomide belongs to a group of immunomodulatory drugs (IMiDs), fi rst known with the discovery of thalidomide in the 1950s, and which have then be tested in various malignancies for their clinical potential. It is described that these IMiDs exhibit multiple biologic effects on cytokine and cell-mediated responses. Lenalidomide was developed by chemical modifi cation of thalidomide to enhance the immunomodulatory potency but minimize the dose-limiting neu- rotoxic effects. This drug seems to have a positive clinical impact on hematologic malignancies including myelodysplastic syndrome, multiple myeloma, and chronic lymphocytic leukemia. Different potential mechanisms are discussed for lenalid- omide, including inhibition of angiogenesis, blockade of various cytokines and enhancement of immune system function. Even with strong improvement of the outcome of multiple myeloma, still most patients relapse and, therefore, drugs with new mechanisms of action are urgently needed to overcome this resistance. As for myelodysplastic syndromes, a heteroge- neous collection of hematopoietic disorders characterized by cytopenia, treatment options also have increased over the past 10 years, but still supportive care, cell-stimulating agents and chemotherapy with little impact on long-term outcome are offered to patients. In this review, we discuss the impact of lenalidomide on relapsed myeloma and transfusion dependent MDS as a novel strategy under assessment in preclinical and clinical trials. It was shown that Lenalidomide had clinical potential in both entities and its effectiveness might be enhanced by the rational combination with conventional agents.

Auf dem Weg zu nutzerzentrierten klinischen Informationssystemen

Zusammenfassung Im Rahmen einer mehrjährigen Zusammenarbeit zwischen der medizinischen Fakultät der Universität Heidelberg und dem Deutschen Forschungszentrum für Künstliche Intelligenz (DFKI) wurde die Situation aktueller medizinischer Softwaresysteme analysiert. Während eines ersten Projektes wurde gemeinsam ein Prototyp eines nutzerzentrierten Softwaresystems für die allogene Stammzelltransplantation entwickelt. Ein darauf aufbauendes zweites Projekt führte eine Befragung unter dem medizinischen Personal zum Stellenwert von IT-Anwendungen im klinischen Alltag durch und analysierte die Situation aktueller medizinischer Softwaresysteme. Neben der Vorstellung der Umfrageergebnisse und Ergebnisse des Demonstrators wird in diesem Beitrag die Frage diskutiert, ob aktuelle medizinische Softwaresysteme die Nutzer genügend bei deren täglichen Arbeit unterstützen, oder ob die Softwaresysteme nur funktionsorientiert und an der Wirklichkeit vorbei entwickelt werden.