Evaluation of incompatible coadministration of continuous intravenous infusions in a pediatric/neonatal intensive care unit

OBJECTIVES: We aimed to evaluate and quantify incompatible coadministrations of continuous intravenous medication in the daily clinical practice of a PICU/NICU. METHODS: We conducted a retrospective, observational study in the setting of an 18-bed PICU/NICU. All concurrently administered continuous infusions, including blood products and parenteral nutrition, were analyzed for 2 months. Raw electronic data were retrieved and subjected to quality controls. Infusion combinations were classified as compatible, incompatible, no data, or variable according to the internal hospital charts, Trissel's database, and the Swiss summary of product characteristics. For situations with incompatible coadministrations, we assessed alternative distributions of infusions among the currently available lumen. RESULTS: Data for 100 patients were analyzed. Patients were exposed to a mean of 6.9 ± 3.6 individual continuous infusions administered through 3.8 ± 1.8 lumina. Among the 1447 coadministered continuous infusions, we detected 146 incompatible combinations (10%), resulting in 105 individually relevant incompatible situations. Furthermore, 185 combinations (13%) were not covered by internal compatibility charts, and for 207 combinations (15%) no data on compatibility were available. We found that 58% of the incompatible situations could have been avoided by a redistribution of the infusions among the available lumina. CONCLUSIONS: Most infusion combinations in the studied PICU/NICU were compatible and covered by the internal compatibility charts. However, we also identified concurrent administrations of incompatible infusions or for which compatibility data are not available. A significant reduction of coadministrations of incompatible infusions could be achieved through optimal use of available lumina

Current Approaches for Image Fusion of Histological Data with Computed Tomography and Magnetic Resonance Imaging

Classical analysis of biological samples requires the destruction of the tissue’s integrity by cutting or grinding it down to thin slices for (Immuno)-histochemical staining and microscopic analysis. Despite high specificity, encoded in the stained 2D section of the whole tissue, the structural information, especially 3D information, is limited. Computed tomography (CT) or magnetic resonance imaging (MRI) scans performed prior to sectioning in combination with image registration algorithms provide an opportunity to regain access to morphological characteristics as well as to relate histological findings to the 3D structure of the local tissue environment. This review provides a summary of prevalent literature addressing the problem of multimodal coregistration of hard- and soft-tissue in microscopy and tomography. Grouped according to the complexity of the dimensions, including image-to-volume (2D ⟶ 3D), image-to-image (2D ⟶ 2D), and volume-to-volume (3D ⟶ 3D), selected currently applied approaches are investigated by comparing the method accuracy with respect to the limiting resolution of the tomography. Correlation of multimodal imaging could position itself as a useful tool allowing for precise histological diagnostic and allow the a priori planning of tissue extraction like biopsies

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

BACKGROUND: Ribavirin (RBV) is an essential component of most current hepatitis C (HCV) treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN) to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR). METHODS: We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS) participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT) 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24) and IL28B genotype (CC versus CT/TT). RESULTS: SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80]) and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73]), regardless of treatment phase, and IL28B genotype. CONCLUSION: In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype

Rivaroxaban postmarketing risk of liver injury

BACKGROUND: Rivaroxaban is an oral direct factor Xa inhibitor that has been marketed worldwide since 2008 for the primary and secondary prevention and treatment of thromboembolic disorders. Although liver injury was observed in premarketing trials of rivaroxaban, there are no published postmarketing cases of liver injury associated with rivaroxaban. METHODS: Report of 14 cases of liver injury associated with rivaroxaban, including two with liver biopsy, and search queries in three large international pharmacovigilance databases for comparable cases. RESULTS: Formal causality assessment classified rivaroxaban as the "highly probable", "probable" and "possible" cause in 4, 7 and 3 patients, respectively. Search results from three large international pharmacovigilance databases revealed a considerable number of additional hepatic adverse events where rivaroxaban was reported as a suspected cause. CONCLUSIONS: We interpret the presented information as a relevant safety signal that should be followed by pharmacoepidemiological studies in order to reliably estimate absolute and relative risks of liver injury associated with rivaroxaban in support of rational risk-benefit assessment. Meanwhile, incident symptoms and signs of liver disease in patients treated with rivaroxaban should be considered as a potential adverse drug reaction, and if no other likely cause can be identified rivaroxaban should be stopped as soon as possible

On the Lagrangian Dynamics of Atmospheric Zonal Jets and the Permeability of the Stratospheric Polar Vortex

The Lagrangian dynamics of zonal jets in the atmosphere are considered, with particular attention paid to explaining why, under commonly encountered conditions, zonal jets serve as barriers to meridional transport. The velocity field is assumed to be two-dimensional and incompressible, and composed of a steady zonal flow with an isolated maximum (a zonal jet) on which two or more travelling Rossby waves are superimposed. The associated Lagrangian motion is studied with the aid of KAM (Kolmogorov--Arnold--Moser) theory, including nontrivial extensions of well-known results. These extensions include applicability of the theory when the usual statements of nondegeneracy are violated, and applicability of the theory to multiply periodic systems, including the absence of Arnold diffusion in such systems. These results, together with numerical simulations based on a model system, provide an explanation of the mechanism by which zonal jets serve as barriers to meridional transport of passive tracers under commonly encountered conditions. Causes for the breakdown of such a barrier are discussed. It is argued that a barrier of this type accounts for the sharp boundary of the Antarctic ozone hole at the perimeter of the stratospheric polar vortex in the austral spring.Comment: Submitted to Journal of the Atmospheric Science

6-thioguanine treatment in inflammatory bowel disease: A critical appraisal by a European 6-TG working party

Recently, the suggestion to use 6-thioguanine (6-TG) as an alternative thiopurine in patients with inflammatory bowel disease (IBD) has been discarded due to reports about possible (hepato) toxicity. During meetings arranged in Vienna and Prague in 2004, European experts applying 6-TG further on in IBD patients presented data on safety and efficacy of 6-TG. After thorough evaluation of its risk-benefit ratio, the group consented that 6-TG may still be considered as a rescue drug in stringently defined indications in IBD, albeit restricted to a clinical research setting. As a potential indication for administering 6-TG, we delineated the requirement for maintenance therapy as well as intolerance and/or resistance to aminosalicylates, azathioprine, 6-mercaptopurine, methotrexate and infliximab. Furthermore, indications are preferred in which surgery is thought to be inappropriate. The standard 6-TG dosage should not exceed 25 mg daily. Routine laboratory controls are mandatory in short intervals. Liver biopsies should be performed after 6-12 months, three years and then three-yearly accompanied by gastroduodenoscopy, to monitor for potential hepatotoxicity, including nodular regenerative hyperplasia (NRH) and veno-occlusive disease (VOD). Treatment with 6-TG must be discontinued in case of overt or histologically proven hepatotoxicity. Copyright (c) 2006 S. Karger AG, Basel

Aplastic anemia associated with interferon alpha 2a in a patient with chronic hepatitis C virus infection: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hepatitis-associated aplastic anemia is a common syndrome in patients with bone marrow failure. However, hepatitis-associated aplastic anemia is an immune-mediated disease that does not appear to be caused by any of the known hepatitis viruses including hepatitis C virus. In addition, to the best of our knowledge there are no reported cases of patients with chronic hepatitis C virus infection developing aplastic anemia associated with pegylated interferon alpha 2a treatment.</p> <p>Case presentation</p> <p>We report the case of a 46-year-old Greek man who developed severe aplastic anemia during treatment with pegylated interferon alpha 2a for chronic hepatitis C virus infection. He presented with generalized purpura and bruising, as well as pallor of the skin and mucous membranes. His blood tests showed pancytopenia. He underwent allogeneic bone marrow transplantation after completing two courses of immunosuppressive therapy with antithymocyte globulin and cyclosporin A.</p> <p>Conclusions</p> <p>The combination of a specific environmental precipitant represented by the hepatitis C virus infection, an altered metabolic detoxification pathway due to treatment with pegylated interferon alpha 2a and a facilitating genetic background such as polymorphism in metabolic detoxification pathways and specific human leukocyte antigen genes possibly conspired synergistically in the development of aplastic anemia in this patient. Our case clearly shows that the causative role of pegylated interferon alpha 2a in the development of aplastic anemia must not be ignored.</p

Hyperimmune anti-HBs plasma as alternative to commercial immunoglobulins for prevention of HBV recurrence after liver transplantation

BACKGROUND: Hepatitis B immune globulins (HBIG) in combination with nucleos(t)ide analogues (NA) are effectively used for the prevention of hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, associated treatment costs for HBIG are exceedingly high. METHODS: Fresh frozen plasma obtained from blood donors with high anti-HBs levels (hyperimmune plasma, HIP) containing at least 4,500 IU anti-HBs was used as alternative treatment for HBV recurrence prophylaxis post-LT. RESULTS: Twenty-one HBV-related LT recipients received HIP starting at transplantation, followed by long-term combination treatment with NA. Mean follow-up time was 4.5 years (range 0.5-12.6) and each patient received on average 8.2 HIP per year (range 5.8-11.4). Anti-HBs terminal elimination kinetic after HIP administration was 20.6 days (range 13.8-30.9), which is comparable to values reported for commercial HBIG products. All 21 patients remained free of HBV recurrence during follow-up and no transfusion-transmitted infection or other serious complication was observed. Seven patients developed reversible mild transfusion reactions. The cost for one HIP unit was USD 140; average yearly HBIG treatment cost was USD 1,148 per patient, as compared to USD 25,000-100,000 for treatment with commercial HBIG. CONCLUSION: The results of this study suggest that the use of HIP may be a useful and economical approach for the prevention of HBV recurrence post-LT if used in combination with NA. Additional prospective controlled studies in larger populations are needed to confirm these results