Therapeutic conflicts in emergency department patients with multimorbidity: a cross-sectional study.

BACKGROUND: Patients with multimorbidity are an increasing concern in healthcare. Clinical practice guidelines, however, do not take into account potential therapeutic conflicts caused by co-occurring medical conditions. This makes therapeutic decisions complex, especially in emergency situations. OBJECTIVE: The aim of this study was to identify and quantify therapeutic conflicts in emergency department patients with multimorbidity. METHODS: We reviewed electronic records of all patients ≥18 years with two or more concurrent active medical conditions, admitted from the emergency department to the hospital ward of the University Hospital Zurich in January 2009. We cross-tabulated all active diagnoses with treatments recommended by guidelines for each diagnosis. Then, we identified potential therapeutic conflicts and classified them as either major or minor conflicts according to their clinical significance. RESULTS: 166 emergency inpatients with multimorbidity were included. The mean number of active diagnoses per patient was 6.6 (SD±3.4). We identified a total of 239 therapeutic conflicts in 49% of the of the study population. In 29% of the study population major therapeutic conflicts, in 41% of the patients minor therapeutic conflicts occurred. CONCLUSIONS: Therapeutic conflicts are common among multimorbid patients, with one out of two experiencing minor, and one out of three experiencing major therapeutic conflicts. Clinical practice guidelines need to address frequent therapeutic conflicts in patients with co-morbid medical conditions.

Prevalence of multimorbidity in medical inpatients.

OBJECTIVE: To validate the estimates of the prevalence of multimorbidity based on administrative hospital discharge data, with medical records and chart reviews as benchmarks. DESIGN: Retrospective cohort study. SETTING: Medical division of a tertiary care teaching hospital. PARTICIPANTS: A total of 170 medical inpatients admitted from the emergency unit in January 2009. MAIN MEASURES: The prevalence of multimorbidity for three different definitions (≥2 diagnoses, ≥2 diagnoses from different ICD-10 chapters, and ≥2 medical conditions as defined by Charlson/Deyo) and three different data sources (administrative data, chart reviews, and medical records). RESULTS: The prevalence of multimorbidity in medical inpatients derived from administrative data, chart reviews and medical records was very high and concurred for the different definitions of multimorbidity (≥2 diagnoses: 96.5%, 95.3%, and 92.9% [p = 0.32], ≥2 diagnoses from different ICD-10 chapters: 86.5%, 90.0%, and 85.9% [p = 0.46], and ≥2 medical conditions as defined by Charlson/Deyo: 48.2%, 50.0%, and 46.5% [p = 0.81]). The agreement of rating of multimorbidity for administrative data and chart reviews and administrative data and medical records was 94.1% and 93.0% (kappa statistics 0.47) for ≥2 diagnoses; 86.0% and 86.5% (kappa statistics 0.52) for ≥2 diagnoses from different ICD-10 chapters; and 82.9% and 85.3% (kappa statistics 0.69) for ≥2 medical conditions as defined by Charlson/Deyo. CONCLUSION: Estimates of the prevalence of multimorbidity in medical inpatients based on administrative data, chart reviews and medical records were very high and congruent for the different definitions of multimorbidity. Agreement for rating multimorbidity based on the different data sources was moderate to good. Administrative hospital discharge data are a valid source for exploring the burden of multimorbidity in hospital settings.

Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vascular endothelial growth factor production by taurolidine.

OBJECT: Taurolidine, a derivative of the amino acid taurin, was recently found to display a potent antineoplastic effect both in vitro and in vivo. The authors therefore initiated studies to assess the potential antineoplastic activity of taurolidine in human glioma cell lines and in ex vivo malignant cell cultures. They also studied the mechanisms that induce cell death and the impact of taurolidine on tumor-derived vascular endothelial growth factor (VEGF) production. METHODS: Cytotoxicity and clonogenic assays were performed using crystal violet staining. In the cytotoxicity assay 100% of glioma cell lines (eight of eight) and 74% of ex vivo glioma cultures (14 of 19) demonstrated sensitivity to taurolidine, with a mean median effective concentration (EC50) of 51 +/- 28 microg/ml and 56 +/- 23 microg/ml, respectively. Colony formation was inhibited by taurolidine, with a mean EC50 of 7 +/- 3 microg/ml for the cell lines and a mean EC50 of 3.5 +/- 1.7 microg/ml for the ex vivo glioma cultures. On observing this high activity of taurolidine in both assays, the authors decided to evaluate its cell death mechanisms. Fragmentation of DNA, externalization of phosphatidylserine, activation of poly(adenosine diphosphate-ribose) polymerase, loss of the mitochondrial membrane potential followed by a release of apoptosis-inducing factor, and typical apoptotic features were found after taurolidine treatment. Cell death was preceded by the generation of reactive O2 intermediates, which was abrogated by N-acetylcysteine but not by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction. CONCLUSIONS: Given all these findings, taurolidine may be a promising new agent in the treatment of malignant gliomas; it displays a combination of antineoplastic and antiangiogenic activities, inducing tumor cell apoptosis and inhibiting tumor-derived VEGF production.