Jf Martinez

Compatibility of Medications With 3-in-1 Parenteral Nutrition Admixtures

BACKGROUND The absence of drug compatibility information with 3-in-1 parenteral nutrition admixtures has been problematic. The purpose of this project was to evaluate the physical compatibility of 106 selected drugs during simulated Y-site injection into nine different 3-in-1 parenteral nutrition admixture formulations. METHODS Four-milliliter samples of each of the representative 3-in-1 parenteral nutrition admixture formulations were combined in a 1:1 ratio with 4-mL samples of each of 106 drugs, including supportive care drugs, anti-infectives, and antineoplastic drugs. Six replicate samples of each combination were prepared. Two samples were evaluated initially after mixing, two more after 1 hour, and the last two after 4 hours at 23 degrees C. At each test interval, the samples were subjected to centrifugation, causing the fat to rise to the top. The top fat layer and most of the aqueous phase were removed, and the remaining liquid was diluted with about 7 mL of particle-free, high-performance liquid chromatography-grade water to facilitate observation of any particulates that might have formed. Visual examinations were performed in normal diffuse fluorescent laboratory light and under high-intensity, monodirectional light. RESULTS Most of the drugs tested were physically compatible with the 3-in-1 parenteral nutrition admixtures for 4 hours at 23 degrees C. However, 23 drugs exhibited various incompatibilities with one or more of the parenteral nutrition admixtures. Six drugs resulted in the formation of precipitate with some or all of the admixtures. Seventeen drugs caused disruption of the emulsion, usually with oiling out. CONCLUSIONS Most of the test drugs were physically compatible with the nine representative 3-in-1 parenteral nutrition admixtures. However, the 23 drugs that resulted in incompatibilities should not be administered simultaneously with the incompatible parenteral nutrition admixtures via a Y injection site.

Spatial habitat features derived from multiparametric magnetic resonance imaging data are associated with molecular subtype and 12-month survival status in glioblastoma multiforme

One of the most common and aggressive malignant brain tumors is Glioblastoma multiforme. Despite the multimodality treatment such as radiation therapy and chemotherapy (temozolomide: TMZ), the median survival rate of glioblastoma patient is less than 15 months. In this study, we investigated the association between measures of spatial diversity derived from spatial point pattern analysis of multiparametric magnetic resonance imaging (MRI) data with molecular status as well as 12-month survival in glioblastoma. We obtained 27 measures of spatial proximity (diversity) via spatial point pattern analysis of multiparametric T1 post-contrast and T2 fluid-attenuated inversion recovery MRI data. These measures were used to predict 12-month survival status (≤12 or >12 months) in 74 glioblastoma patients. Kaplan-Meier with receiver operating characteristic analyses was used to assess the relationship between derived spatial features and 12-month survival status as well as molecular subtype status in patients with glioblastoma. Kaplan-Meier survival analysis revealed that 14 spatial features were capable of stratifying overall survival in a statistically significant manner. For prediction of 12-month survival status based on these diversity indices, sensitivity and specificity were 0.86 and 0.64, respectively. The area under the receiver operating characteristic curve and the accuracy were 0.76 and 0.75, respectively. For prediction of molecular subtype status, proneural subtype shows highest accuracy of 0.93 among all molecular subtypes based on receiver operating characteristic analysis. We find that measures of spatial diversity from point pattern analysis of intensity habitats from T1 post-contrast and T2 fluid-attenuated inversion recovery images are associated with both tumor subtype status and 12-month survival status and may therefore be useful indicators of patient prognosis, in addition to providing potential guidance for molecularly-targeted therapies in Glioblastoma multiforme.

Rapid loss of fentanyl citrate admixed with fluorouracil in polyvinyl chloride containers.

Objective To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with fentanyl citrate 12.5 μg/mL in dextrose 5% and in sodium chloride 0.9% injection. Design Test solutions of the drugs in dextrose 5% injection and in sodium chloride 0.9% injection were prepared in triplicate and stored at −20, 4, 23, and 32 °C. Samples were removed immediately and at various times over 7 days and stored at −70 °C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter; particle content was measured with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. Results Fentanyl citrate was rapidly lost when admixed with fluorouracil in polyvinyl chloride (PVC) containers, losing about 25% in the first 15 minutes and about 50% in the first hour. The loss of fentanyl citrate was so rapid that accurate time zero determinations were not possible. The extent of fentanyl loss increased with time and occurred more rapidly at the higher temperatures (i.e., 23,32 °C). Losses of 70% or more occurred in all samples within 24 hours. Fentanyl underwent rapid sorption to the containers at the high pH (9.0–9.5) of the fluorouracil admixtures. Adjusting the pH of a fentanyl citrate solution (containing no fluorouracil) in PVC containers to pH 9 with sodium hydroxide also resulted in rapid sorption loss. Fentanyl citrate sorption did not occur when admixtures were prepared in polyethylene containers. Fluorouracil remained stable for at least 7 days at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the test solutions at any time. Conclusions When admixed with fluorouracil 1 and 16 mg/mL in dextrose 5% injection and sodium chloride 0.9% injection, fentanyl citrate 12.5 μg/mL underwent rapid and extensive loss due to sorption to the PVC containers, making the combination unacceptable within minutes of mixing. The sorption results from the alkaline pH of the admixture and, presumably, could occur from the admixture of fentanyl citrate with any sufficiently alkaline drug.

Stability and Compatibility of Fluorouracil with Morphine Sulfate and Hydromorphone Hydrochloride

OBJECTIVE: To study the physical compatibility and chemical stability of fluorouracil 1 and 16 mg/mL with morphine sulfate 1 mg/mL and with hydromorphone hydrochloride 0.5 mg/mL in dextrose 5% injection and in NaCl 0.9% injection. DESIGN: Test solutions of the drugs in dextrose 5% and in NaCl 0.9% were prepared in triplicate and stored at −20, 4, 23, and 32°C. Samples were removed immediately and at various time points over 35 days and stored at −70 °C until analyzed. Physical compatibility was assessed visually and by measuring turbidity with a color-correcting turbidimeter and particle content with a light-obscuration particle sizer and counter. Chemical stability was determined by measuring the concentration of each drug in the test solutions in duplicate with stability-indicating HPLC. RESULTS: The morphine test solutions all rapidly developed crystalline precipitation when admixed with fluorouracil. Further, substantial loss of morphine content, usually around 60-80%, occurred in all samples within 24 hours at all temperatures. There were no visual or subvisual changes in turbidity or particle content in any of the fluorouracil with hydromorphone test solutions at any of the time points. Further, there was no loss of fluorouracil over 7 days at 32 °C and 35 days at 23, 4, and −20 °C. Hydromorphone also was stable for 7 days at 32 °C and for 35 days at the other temperatures when combined with fluorouracil 1 mg/mL and at −20 and 4 °C with fluorouracil 16 mg/mL. However, with fluorouracil 16 mg/mL, hydromorphone was stable only for 3 days at 32 °C and for 7 days at 23 °C, exhibiting approximately 10% loss after those times. CONCLUSIONS: When admixed in dextrose 5% injection and NaCl 0.9% injection, fluorouracil 1 and 16 mg/mL and morphine 0.5 mg/mL were immediately physically incompatible in all samples resulting in substantial loss of morphine content as precipitated crystals. Fluorouracil 1 mg/mL plus hydromorphone 0.5 mg/mL were compatible and stable for at least 7 days at 32 °C and for at least 35 days at 23, 4, and −20 °C. Admixed with fluorouracil 16 mg/mL, hydromorphone was stable for 3 days at 32 °C, 7 days at 23 °C, and 35 days at 4 and −20 °C.

Compatibility of Gemcitabine Hydrochloride with 107 Selected Drugs During Simulated Y-Site Injection

OBJECTIVE To evaluate the physical compatibility of gemcitabine hydrochloride (Gemzar-Eli Lilly and Company) with 107 selected drugs. DESIGN Controlled experimental trial. SETTING Laboratory. INTERVENTIONS Samples of 5 mL gemcitabine (as the hydrochloride salt) 10 mg/mL in 0.9% sodium chloride injection were mixed with 5 mL samples of the selected drugs diluted in 0.9% sodium chloride injection or, if necessary to avoid incompatibilities with the diluent, 5% dextrose injection. MAIN OUTCOME MEASURES Visual examinations of the samples were performed in normal fluorescent light with the unaided eye and using a Tyndall beam (high-intensity monodirectional light) to enhance visualization of small particles and low-level haze. The turbidity of each sample was measured as well. In selected samples, electronic particle content assessment was performed. All of the samples were assessed initially and at 1 and 4 hours. RESULTS Most of the drugs were physically compatible with gemcitabine hydrochloride during the 4-hour observation period. However, 15 drug combinations had incompatibilities that included color change, increase in haze or turbidity, particulate formation, and gross precipitation: acyclovir sodium, amphotericin B, cefoperazone sodium, cefotaxime sodium, furosemide, ganciclovir sodium, imipenem-cilastatin sodium, irinotecan, methotrexate sodium, methylprednisolone sodium succinate, mezlocillin disodium, mitomycin, piperacillin sodium, piperacillin sodium/tazobactam sodium, and prochlorperazine edisylate. CONCLUSION Gemcitabine hydrochloride 10 mg/mL admixed in a compatible infusion solution is physically compatible for 4 hours at room temperature with 92 of 107 tested drugs. Simultaneous Y-site administration of gemcitabine hydrochloride with the 15 drugs resulting in incompatibilities should be avoided.

Compatibility of Etoposide Phosphate with Selected Drugs During Simulated Y-Site Injection

OBJECTIVE To evaluate the physical compatibility of etoposide phosphate with 101 selected secondary drugs, including antineoplastic chemotherapy agents, anti-infectives, and supportive care drugs, during simulated Y-site injection. DESIGN Five-milliliter samples of etoposide 5 mg/mL as phosphate in 5% dextrose injection were mixed with 5 mL of the selected drugs diluted in 5% dextrose injection or, if necessary to avoid incompatibilities with the diluent, 0.9% sodium chloride injection. Samples were examined visually in normal fluorescent light with the unaided eye and using a Tyndall beam (high-intensity monodirectional light) to enhance the visibility of small particles and low-level haze. Turbidity of each sample was measured. In selected samples, electronic particle content assessment was performed. All of the samples were assessed initially and at one and four hours. RESULTS Most of the secondary drugs were physically compatible with etoposide phosphate during the four-hour observation period. However, seven drug combinations had incompatibilities that included color change, increase in haze or turbidity, particulate formation, and gross precipitation. The drugs that were observed to be physically incompatible with etoposide phosphate were amphotericin B, cefepime hydrochloride, chlorpromazine hydrochloride, imipenem-cilastatin sodium, methylprednisolone sodium succinate, mitomycin, and prochlorperazine edisylate. CONCLUSION Etoposide 5 mg/mL as phosphate in 5% dextrose injection is physically compatible for four hours at room temperature during simulated Y-site administration with 94 of the 101 drugs selected. Simultaneous Y-site administration of etoposide phosphate with the seven incompatible drugs should be avoided.

Stability of busulfan injection admixtures in 5 % dextrose injection and 0.9% sodium chloride injection:

Objective. The purpose of this study was to deter mine the stability of busulfan injection at 0.5 and 0.1 mg/mL admixed in 5% dextrose injection and 0.9% sodium chloride injection in PVC and polyolefm bags over 24 hours at 23°C. Methods. The busulfan injection was prepared by dissolving the bulk powder in a 1:2 mixture of N,N-dimethylacetamide and polyethylene glycol 400 to form a 6 mg/mL solution. The injection was filtered and admixed in the infusion solutions to yield busulfan concentrations of 0.5 and 0.1 mg/mL. Evaluations were performed initially and after 4, 8, and 24 hours of storage for physical and chemical stability. The admix tures were evaluated for physical stability using visual observation in normal light and using a high-intensity monodirectional light beam as well as measuring turbidity. The chemical stability was evaluated by using a stability-indicating HPLC analytical technique. Results. No physical instabilities were observed. However, busulfan is chemically unstable. At 0.5 mg/mL, potency of at least 95% was retained through 4 hours and at least 90% was retained through 8 hours. After 24 hours, losses of 20% to 30% occurred. At 0.1 mg/mL, drug loss was more rapid. Potency of at least 90% was retained through 4 hours. Losses after 24 hours were about 30% to 40%. Conclusions. Busulfan injection admixed in 5% dextrose injection or 0.9% sodium chloride injection is unstable. At a concentration of 0.5 mg/mL, ade quate drug delivery is provided within 8 hours of admixture. At the lower concentration of 0.1 mg/mL, adequate drug delivery is only provided for 4 hours.

DEMARCATE: Density-based magnetic resonance image clustering for assessing tumor heterogeneity in cancer

Tumor heterogeneity is a crucial area of cancer research wherein inter- and intra-tumor differences are investigated to assess and monitor disease development and progression, especially in cancer. The proliferation of imaging and linked genomic data has enabled us to evaluate tumor heterogeneity on multiple levels. In this work, we examine magnetic resonance imaging (MRI) in patients with brain cancer to assess image-based tumor heterogeneity. Standard approaches to this problem use scalar summary measures (e.g., intensity-based histogram statistics) that do not adequately capture the complete and finer scale information in the voxel-level data. In this paper, we introduce a novel technique, DEMARCATE (DEnsity-based MAgnetic Resonance image Clustering for Assessing Tumor hEterogeneity) to explore the entire tumor heterogeneity density profiles (THDPs) obtained from the full tumor voxel space. THDPs are smoothed representations of the probability density function of the tumor images. We develop tools for analyzing such objects under the Fisher–Rao Riemannian framework that allows us to construct metrics for THDP comparisons across patients, which can be used in conjunction with standard clustering approaches. Our analyses of The Cancer Genome Atlas (TCGA) based Glioblastoma dataset reveal two significant clusters of patients with marked differences in tumor morphology, genomic characteristics and prognostic clinical outcomes. In addition, we see enrichment of image-based clusters with known molecular subtypes of glioblastoma multiforme, which further validates our representation of tumor heterogeneity and subsequent clustering techniques.

NCO-11TUMOR VOLUMETRIC AND TEXTURAL FEATURE PREDICTORS OF NEUROCOGNITIVE IMPAIRMENT IN PATIENTS WITH TEMPORAL LOBE GLIOMA

BACKGROUND: To determine whether computationally derived image-based textural and volumetric tumor features can predict cognitive impairment in patients with temporal lobe glioma. METHODS: Treatment naive patients with glioma (n = 69; 64% glioblastoma; 74% left temporal) completed neurocognitive testing [WAIS-III Digit Span (DS); Controlled Oral Word Association (COWA); HVLT-R Total Recall; Trail Making Test A & B (TMT)]. Demographically adjusted scores that were at or below 0.74). Volumetric and textural tumor features appear predictive of neurocognitive impairment in patients with glioma, with inclusion of textural indices conveying at least marginal improvement in classification accuracy.