Push Injection Research Articles

Randomized controlled trial on the effect of 1-hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis).

Vincristine is an integral component of treatment for children with cancer. Its main dose-limiting side effect is vincristine-induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1-hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short-term outcomes (median follow-up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1-hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow-up 20 months), which includes treatment outcome as a secondary objective (follow-up 3 years). VIPN was measured 1-7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric-modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed. Forty-five participants per randomization group were included. There was no significant effect of 1-hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one-hour group (rate ratio 0.52, 95% confidence interval 0.33-0.80, p = 0.003). Four patients in the one-hour group and one patient in the push group relapsed. Two patients in the one-hour group died. 1-hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1-hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.

Testing of a novel multi-branch horizontal well remediation technology for in situ remediation of contaminated soil and groundwater

Soil and groundwater contamination has become a key issue in urban redevelopment. It is particularly difficult to use heavy equipment for the remediation of restricted sites or areas contaminated by factories that are still in operation. In this case, horizontal wells are considered a potentially useful technology as they can potentially remediate contamination areas located below buildings and other surface/subsurface obstacles. This research first introduces the principles and advantages and disadvantages of direct push injection, improved slant well, high-pressure rotary jet technology, horizontal reactive media treatment wells, and horizontal directional drilling well. The key aspects for promising in-situ remediation techniques were summarized as remediation well design, remediation agent injection technology and drill pipe and well wall sealing technology. Based on the requirements for key technologies, a novel multi-branch horizontal well in-situ remediation process was proposed, which integrates vertical/horizontal directional drilling, rotary injection, and expansion sealing techniques, and relevant supporting drilling and injecting equipment were developed. A bench test and field test were conducted to test drilling tool performance, drilling accuracy, and injection radius of influence. The results showed that the developed supporting drilling tool met the process requirements and could complete multi-branch horizontal well remediation engineering construction. The deviation between the measured depth and the design depth of the multi-branch horizontal well constructed using this technology was less than 9%, and the deviation between the depth displayed by the guidance instrument and the measured depth was less than 1%. The injection radius of influence in the test field measured from the monitoring wells was greater than or equal to 5 m. The results of this research can provide an effective method for the remediation of contaminated sites.

The comparison of different drip cholangiography: a randomised trial.

This study investigated the advantages and disadvantages of contrast media administration by gravity drip and manual push injection during cholangiography. A total of 100 patients who presented to the Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, for a cholangiography between June 2019 to June 2020 were enrolled in this study. Patients were randomly divided into 2 treatment groups. One group of patients with manual injection of contrast (the N group, n=50), received the contrast agent via the traditional manual injection method whereby the doctor injects 50 mL of prepared contrast agent into the right side of the patient while continuously observing the effects on the bile duct. The other group of patients with gravity drip administration of contrast media (the O group, n=50), received the contrast agent via gravity drip at a rate of 80 drops per minute, and both clinicians and radiologists monitored the entire cholangiography process from a safe distance. Patients were followed up and angiographic satisfaction was assessed after two weeks. All 100 patients completed cholangiography without allergic reaction to the contrast medium. In the traditional injection group (N group), nine patients experienced upper abdominal discomfort with nausea, abdominal pain, chills, high fever, and other symptoms, and residual gallstones were observed in 12 patients. In patients in the gravity drip group (O group), four patients felt upper abdominal discomfort accompanied by nausea, abdominal pain, chills, high fever, and other symptoms, with residual gallstones detected in six patients. Patients who underwent gravity drip cholangiography had significantly reduced adverse reactions compared to patients who underwent traditional manual infusion cholangiography. Furthermore, gravity drip cholangiography resulted in clearer images and reduced X-ray exposure for medical staff. Thus, increased implementation of gravity drip cholangiography in the clinical setting should be considered. Chinese Clinical Trial Registry ChiCTR1800018202.

The Effect of Heterogeneity on the Distribution and Treatment of PFAS in a Complex Geologic Environment

Per-and polyfluoroalkyl substances (PFAS) have been identified as emerging contaminants of concern in the environment in a wide variety of media including groundwater. Typically, PFAS-impacted groundwater is extracted by pump and treat systems and treated using sorptive media such as activated carbon and ion exchange resin. Pump and treat systems are generally considered ineffective for the remediation of dissolved phase contaminants including PFAS but instead are considered applicable for plume containment. An alternative to pump and treat is in-situ treatment. The demonstrated use of in-situ treatment for PFAS-impacted groundwater is limited with only colloidal activated carbon (CAC) being shown to effectively attenuate PFAS over short and moderate time periods. Active research topics for the in-situ treatment of PFAS include the effect of heterogeneity on the distribution of the CAC, the lifespan of the CAC itself, the effect of competitive adsorption/absorption, and the effect of other geochemical conditions on the removal process. This study looked at the effect of heterogeneity on the distribution of CAC and subsequent treatment of PFAS at a site with a multiple aquifer system. The site’s geology varied from a silty sand to sand to fractured bedrock with all three units being impacted by PFAS and benzene (B), toluene (T), ethylbenzene (E), and xylene (X). Parameters evaluated included the distribution of the CAC as well as the subsequent treatment of the PFAS and BTEX. Results of groundwater sampling indicated that the PFAS detected within the groundwater were treated effectively to below their respective reporting limits for the duration of the 1-year test in both the silty sand and sand aquifers. The PFAS in the fractured rock aquifer showed a different treatment profile with longer carbon chained PFAS being attenuated preferentially compared to the shorter carbon chained PFAS. These results suggest that competitive sorptive reactions were occurring on the CAC within the fractured rock. Analysis of the unconsolidated aquifer materials determined that direct push injection of the CAC was effective at delivering the CAC to the target injection zones with post-injection total organic carbon (TOC) concentrations increasing by up to three orders of magnitude compared to pre-injection TOC concentrations. Heterogeneity did have an impact on the CAC distribution with higher hydraulic conductivity zones receiving more CAC mass than lower hydraulic conductivity zones.

Gravity dependent and hand held ‘push’ injection method of contrast cholangiography: A pilot study comparing outcomes and efficacy

Contrast cholangiograms still continue to be obtained prior to removal of intraoperatively or preoperatively placed intra-biliary tubes to look for filling defects, anastomotic leaks or stenosis, evaluation of radiological intervention or a controlled external biliary fistula. Post-cholangiogram cholangitis remains a major morbidity concern. Is it related to the technique? An observational prospective pilot study comparing hand held push injection (PIC) and gravity dependent (GDC) techniques of cholangiography in 30 consecutive patients with in-situ biliary tubes after administration of pre-procedure antibiotic, excluding patients with active cholangitis or complete biliary obstruction. In GDC group, dye was delivered under gravity from a height of 25 cm instead of injection. Outcomes analysed included adverse reactions - minor (two or more of low grade fever, tachycardia, pain/nausea without fever, subclinical cholangitis) and major (two or more of high grade fever, chills, tachycardia, hypotension, oliguria), readmission requirement, and the efficacy (opacification of the biliary tree and demonstration of the objective). In the PIC group (n = 14), adverse reactions were minor in 6 (42.8%) and major in 4 (28.5%). Two patients required re-admission, and in two others discharge from the hospital was delayed. In the GDC group (n=16), adverse reactions were minor in 7 (43.7%), with no major adverse reaction or readmission. Major adverse reactions were significantly more common in PIC as compared to GDC (28.5% vs. 0% respectively, p-value = 0.03), and translated into higher treatment costs. When required, GDC, limiting rise in intrabiliary pressure, is a safer, completely efficacious and economical technique.

The in situ treatment of Basic Violet 16 synthetic dye in groundwater

AbstractSynthetic dyes have been shown to be micropollutants in various aquatic and groundwater systems, often occurring at milligram per liter (mg/L) concentrations. Synthetic dyes are typically introduced into the environment either as a continuous stream from wastewater or as episodic events related to the disposal of residues or spills generated during the manufacturing process. Various studies for the treatment of synthetic dyes have been undertaken for wastewater but studies for the in situ treatment of synthetic dyes in groundwater are limited. A pilot‐scale test was conducted to determine if the use of colloidal activated carbon (CAC) could effectively reduce dissolved concentrations of the synthetic dye Basic Violet (BV16) in groundwater using in situ methods. The pilot test was carried out downgradient of a textile manufacturing facility where historic disposal practices resulted in the release of various chemicals of concern including BV16 to an unconfined silty sand aquifer. A 10‐weight percent CAC solution was injected into a series of temporary direct push injection points to target the synthetic dye that was present at concentrations of up to 1,640 micrograms per liter (μg/L) during the 738‐day study. The results from the pilot test indicated that the CAC was effectively delivered to the target injection zone resulting in a three order of magnitude increase in total organic carbon (TOC) concentrations compared to preinjection TOC concentrations within the aquifer. Distribution of the CAC within the targeted injection zone indicated that heterogeneity affected the distribution with a zone of higher horizontal hydraulic conductivity (KH) having an average TOC concentration approximately 100 percent greater than the mean TOC concentration within the surrounding aquifer targeted by the CAC injection. Analyses of the groundwater chemistry before and postinjection indicated that the CAC had no detrimental impact on the groundwater quality while reducing the concentration of dissolved BV16 within the plume to below the method detection limits within 62 days of injection. The concentration of BV16 remained below the method detection limit of 10 µg/L for the 738‐day duration of the study apart from one detection of 180 µg/L at Day 183 within groundwater sampled from one monitoring well suggesting that the CAC was effective in attenuating the BV16 over the short and moderate term.

A Comparison of Six Transport Models of the MADE-1 Experiment Implemented With Different Types of Hydraulic Data.

Six conceptually different transport models were applied to the macrodispersion experiment (MADE)‐1 field tracer experiment as a first major attempt for model comparison. The objective was to show that complex mass distributions in heterogeneous aquifers can be predicted without calibration of transport parameters, solely making use of structural and flow data. The models differ in their conceptualization of the heterogeneous aquifer structure, computational complexity, and use of conductivity data obtained from various observation methods (direct push injection logging, DPIL, grain size analysis, pumping tests and flowmeter). They share the same underlying physical transport process of advection by the velocity field solely. Predictive capability is assessed by comparing results to observed longitudinal mass distributions of the MADE‐1 experiment. The decreasing mass recovery of the observed plume is attributed to sampling and no physical process like mass transfer is invoked by the models. Measures like peak location and strength are used in comparing the modeled and measured plume mass distribution. Comparison of models reveals that the predictions of the solute plume agree reasonably well with observations, if the models are underlain by a few parameters of close values: mean velocity, a parameter reflecting log‐conductivity variability, and a horizontal length scale related to conductivity spatial correlation. The robustness of the results implies that conservative transport models with appropriate conductivity upscaling strategies of various observation data provide reasonable predictions of plumes longitudinal mass distribution, as long as key features are taken into account.

Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology: A Randomized Controlled Trial Comparing Push Injections with One-Hour Infusions (The VINCA Trial).

Simple SummaryWe studied children with cancer who receive vincristine chemotherapy as a one-hour infusion and compared them to children who received vincristine as a push injection. We investigated if there was a difference in the development of vincristine induced peripheral neuropathy, the most common side effect of vincristine. We found that in general there were no differences between the two groups (one-hour group versus push group). However, in children using both vincristine and azole antifungals, we noticed that children who received vincristine as a one-hour infusion experienced less severe vincristine induced peripheral neuropathy compared to children who received vincristine as a push injection. Therefore, in children who require both azole antifungal medication as well as vincristine it might be beneficial to administer the vincristine as a one-hour infusion instead of a push injection. However, this finding needs to be confirmed in other studies as well.Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). In this study we investigated if one-hour infusions of VCR instead of push-injections reduces VIPN in pediatric oncology patients. We conducted a multicenter randomized controlled trial in which participants received all VCR administrations through push injections or one-hour infusions. VIPN was measured at baseline and 1–5 times during treatment using Common Terminology Criteria of Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score. Moreover, data on co-medication, such as azole antifungals, were collected. Overall, results showed no effect of administration duration on total CTCAE score or ped-mTNS score. However, total CTCAE score was significantly lower in patients receiving one-hour infusions concurrently treated with azole antifungal therapy (β = -1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VCR push injections in pediatric oncology patients. However, one-hour infusions lead to less severe VIPN compared to push-injections when azole therapy is administered concurrently with VCR. These results indicate that in children treated with VCR and requiring concurrent azole therapy, one-hour infusions might be beneficial over push injections, although larger trials are needed to confirm this association.

Comparison of the efficacy of an infusion pump or standard IV push injection to deliver naloxone in treatment of opioid toxicity

Background:The optimal goal of naloxone infusion in intensive care units is to ameliorate opioid-induced side effects in therapy or eliminate the symptoms of opioid toxicity in overdoses. Accurately monitoring and regulating the doses is critical to prevent adverse effects related to naloxone administration. The present study aimed to compare treatment outcomes when using two methods of intravenous naloxone infusion: an infusion pump or the standard method. Methods:This study involved 80 patients with signs and symptoms of opioid overdose. The patients were randomly assigned into two groups with respect to intravenous infusion of naloxone by either an infusion pump or the standard method. Results:Comparison of study parameters between the two groups at 12 and 24 hours after intervention showed significantly more compensatory acid-base imbalance in the naloxone infusion pump group. In the group that received naloxone by pump, only one patient experienced withdrawal symptoms, but withdrawal symptoms appeared in 12 patients (30.0%) in the standard intravenous infusion group within 12 hours and in seven additional patients (17.5%) within 24 hours of intervention. In the group receiving pump-based naloxone infusion therapy, no another complications were reported; however in the standard infusion group, the 12-hour and 24-hour complication rates were 55.0% and 32.5%, respectively. The length of hospital stay was 2.85±1.05 and 4.22±0.92 days for the pump and standard infusion groups, respectively (P<0.001). Conclusions:Naloxone infusion using an infusion pump may be safer with regard to hemodynamic stability, resulting in shorter hospitalization periods, and fewer posttreatment complications.

Vincristine-Induced Peripheral Neuropathy in Pediatric Oncology Patients Receiving Vincristine through Push Injections or One-Hour Infusions: Results of a Randomized Clinical Trial

Purpose Vincristine (VCR) is frequently used for the treatment of pediatric cancer. However, it can lead to dose-limiting vincristine-induced peripheral neuropathy (VIPN). This study aimed to investigate if prolonging the duration of VCR administration (1-hour infusions instead of push injections) reduces VIPN in children with cancer during the first year of treatment. Methods The VINCA trial is an international multicenter randomized controlled trial. Participants were randomized to receive all VCR administrations through push injections or 1-hour infusions. Dose of VCR was 1.5-2 mg/m2 with a maximum of 2 mg. VIPN measurements were performed at baseline and 1-3 times during treatment, depending on the number of VCR administrations and the total treatment time, using 4 items of the common toxicity criteria of adverse events (CTCAE version 4.03): constipation, peripheral sensory neuropathy, peripheral motor neuropathy and neuralgia. Individual item scores range from zero (no complaints) to five (death). The primary outcome of this trial was total sum CTCAE score during first year of treatment. For the current analysis, patients treated for acute lymphoblastic leukemia (ALL) or Hodgkin's lymphoma were included. All included patients were analyzed according to the intention-to-treat principle. Besides VIPN measurements, data on all relevant co-medication during treatment were collected, including data of concurrent azole therapy (as azole treatment is known to interact with VCR treatment). Descriptive data were analyzed using either chi-square tests or t-tests. Longitudinal data were analyzed using repeated measures mixed model analysis for continuous outcomes (total CTCAE sum score) and generalized estimating equations for dichotomous outcomes (having VIPN yes or no, with VIPN defined as a CTCAE score of ≥ 2 on any of the 4 CTCAE items). Patients were considered to have been treated with concurrent azole therapy when azoles were used during the week before or following VCR administration and if ≥ 50% of VCR administrations between two succeeding measurements were given with concurrent azole therapy. Results were corrected for concurrent azole therapy, cumulative VCR dose, disease, age, gender, ethnicity and time since diagnosis. Results In total 90 children (n=45 one hour infusions group, n=45 push injections group) participated in the study, 58 (64%) with ALL and 18 (20%) with HL. Participants in the two randomization groups did not significantly differ regarding gender, age, ethnicity, diagnosis, or cumulative VCR dose. Overall results showed no effect of randomization on total CTCAE score (β=0.07, 95% confidence interval (CI) -0.42-0.56, p=0.78). However, concurrent azole treatment appeared to be an effect modifier in this analysis and therefore results are reported separately for measurements with (n=24) and without concurrent azole therapy (n=226). Among patients who received concurrent azole therapy, total CTCAE sum score was significantly higher in the push group compared to the 1-hour group (β=1.95, 95% CI 0.49-3.41, p=0.01), while among those without concurrent azole therapy, these CTCAE sum scores did not differ between the two randomization groups (β=-0.17, 95% CI: -0.67-0.34, p=0.52). The risk of developing VIPN (no/yes) did not significantly differ between both randomization groups, irrespective whether concurrent azole treatment was given or not (with azole: OR (95% CI)=4.92 (0.60-40.37), p=0.14; without azole: OR (95% CI)=0.97 (0.51-1.82, p=0.92). Conclusions Overall, administration method of VCR given as push injection or 1-hour infusion did not seem to affect the risk of developing VIPN in children treated for ALL or HL when using the current dosing regimen. However, when concurrent azole treatment is given, total CTCAE scores are significantly lower in children in the 1-hour infusion group compared to the push injection group, demonstrating less VIPN. These results indicate that for children treated with VCR and concurrent azole therapy for the prevention or treatment of fungal infections, administration of VCR by 1-hour infusions instead of push injections is recommended. Figure Disclosures Kaspers: Helsinn Healthcare: Consultancy; Boehringer Ingelheim Pharma: Other: Member of a DSMC. van der Sluis:medac: Consultancy; jazz farmaceuticals: Consultancy.

Long‐term evaluation of an EHC injection permeable reactive barrier in a sulfate‐rich, high‐flow aquifer

AbstractPermeable reactive barriers (PRBs) have traditionally been constructed via trenching backfilled with granular, long‐lasting materials. Over the last decade, direct push injection PRBs with fine‐grained injectable reagents have gained popularity as a more cost‐efficient and less‐invasive approach compared to trenching. A direct push injection PRB was installed in 2005 to intercept a 2,500 feet (760 meter) long carbon tetrachloride (CT) groundwater plume at a site in Kansas. The PRB was constructed by injecting EHC® in situ chemical reduction reagent slurry into a line of direct push injection points. EHC is composed of slow‐release plant‐derived organic carbon plus microscale zero‐valent iron (ZVI) particles, specifically formulated for injection applications. This project was the first full‐scale application of EHC into a flow‐through reactive zone and provided valuable information about substrate longevity and PRB performance over time. Groundwater velocity at the site is high (1.8 feet per day) and sulfate‐rich (~120 milligrams per liter), potentially affecting the rate of substrate consumption and the PRB reactive life. CT removal rates peaked 16 months after PRB installation with &gt;99% removal observed. Two years post‐installation removal rates decreased to approximately 95% and have since stabilized at that level for the 12 years of monitoring data available after injection. Geochemical data indicate that the organic carbon component of EHC was mostly consumed after 2 years; however, reducing conditions and a high degree of chloromethane treatment were maintained for several years after total organic carbon concentrations returned to background. Redox conditions are slowly reverting and have returned close to background conditions after 12 years, indicating that the PRB may be nearing the end of its reactive life. Direct measurements of iron have not been performed, but stoichiometric demand calculations suggest that the ZVI component of EHC may, in theory, last for up to 33 years. However, the ZVI component by itself would not be expected to support the level of treatment observed after the organic carbon substrate had been depleted. A longevity of up to 5 years was originally estimated for the EHC PRB based on the maximum expected longevity of the organic carbon substrate. While the organic carbon was consumed faster than expected, the PRB has continued to support a high degree of chloromethane treatment for a significantly longer time period of over 12 years. Recycling of biomass and the contribution from a reduced iron sulfide mineral zone are discussed as possible explanations for the sustained reducing conditions and continued chloromethane treatment.

The in situ treatment of synthetic musk fragrances in groundwater

AbstractSynthetic musk fragrances (SMFs) have been shown to be micropollutants in various aquatic and groundwater systems, often occurring at microgram per liter concentrations. Studies have shown that the most commonly detected SMFs in water are nitro musks and polycyclic musks. The SMFs are typically introduced into the environment in continuous streams such as from wastewater and land application of wastewater or sludge generated during wastewater treatment. Various studies for the treatment of SMFs have been undertaken for wastewater but studies for the treatment of SMFs in groundwater are limited, especially for in situ treatment. A pilot‐scale test was conducted to determine if the use of colloidal activated carbon (CAC) could effectively reduce dissolved concentrations of nitro and polycyclic synthetic musk compounds including musk xylene, musk ketone, galaxolide, and tonalide. The pilot test was carried out downgradient of a septic system in Central Canada where a series of nitrification and denitrification reactions are occurring in an unconfined aquifer. A 10‐weight percent CAC solution was injected into a series of temporary direct push injection points to target the synthetic musk plume. The plume contained galaxolide and tonalide concentrations up to 687 and 187 nanograms per liter (ng/L), respectively, while the concentrations of musk ketone and musk xylene were below the method detection limit (20 ng/L). A total of 13,950 liters of CAC solution was injected during one injection event. The pilot test results indicated that the CAC was effectively delivered to the target injection zone resulting in an increase in total organic carbon concentrations within the saturated soil greater than two orders of magnitude compared to the background concentrations. Analyses of the groundwater chemistry before and post‐injection indicated that the CAC had no detrimental impact on the groundwater quality while reducing the concentration of dissolved galaxolide and tonalide within the plume to below the method detection limits within 51 days of injection with the exception of two of the 14 wells monitored which had galaxolide and tonalide concentrations up to 78 and 35 ng/L. Within 6 months of application, the concentrations of galaxolide and tonalide had decreased to below the method detection limits. Subsequent monitoring of the groundwater quality over a one‐year period failed to detect galaxolide and tonalide, suggesting that the CAC was effective in attenuating the galaxolide and tonalide.

Simulation Assessment of Direct Push Injection Logging for High-Resolution Aquifer Characterization.

Direct push injection logging (DPIL) has become one of the most widely used approaches for obtaining vertical profiles of hydraulic conductivity (K) in environmental site investigations. Despite its widespread use, however, there has been no rigorous analysis of the underlying physical processes that take place during DPIL or how the approach would perform under different hydrogeological and operating conditions. We address these issues through a series of numerical simulations. Results show that the ratio of DPIL injection rate over pressure can be used for direct determination of K when K is >10-6 m/s. When K is <10-6 m/s and specific storage (Ss) is >10-3 /m, the ratio becomes increasingly sensitive to Ss; in that case, additional information on Ss is needed for reliable K estimation. For unconsolidated formations of moderate K or higher, the ratio of injection rate over pressure should provide a reasonable K estimate when Ss is <10-3 /m. Although water injection at previous depths during continuous DPIL has only a small impact on the pressure response measured at the current injection depth, probe advancement can have a significant impact when K and Ss are small. Consequently, in fine-grained materials, the advancement-generated pore water pressure increase can comprise a large portion of the measured pressure response. To diminish the impact of probe advancement in such materials, advancement speed should be kept as low as possible (e.g., 0.5cm/s).

Investigation of chlorinated solvent pollution with resistivity and induced polarization

Globally, an enormous number of polluted areas are in need of remediation to prevent adverse effects on health and environment. In situ remediation and especially the monitoring thereof needs further development to avoid costly and hazardous shipments associated with excavation. The monitoring of in situ remediation actions needs easier and cheaper nondestructive methods for evaluation and verification of remediation degree and degradation status of the contaminants. We investigate the Direct Current resistivity and time-domain Induced Polarization tomography (DCIP) method and its use within the context of a DNAPL (Dense Non-Aqueous Phase Liquids) contaminated site in Varberg, Sweden, where an in situ remediation pilot test has been performed by stimulated reductive dechlorination by push injection. Our results show that the DCIP technique is an emerging and promising technique for mapping of underground structures and possibly biogeochemical spatial and temporal changes. The methodology could in combination with drilling, sampling and other complementary methods give an almost continuous image of the underground structures and delineation of the pollutant situation. It can be expected to have a future in monitoring approaches measuring time lapse induced polarization (IP), if more research is performed on the parameters and processes affecting the IP-signals verifying the interpretations. The IP technique can possibly be used for verification of the effectiveness of in situ remediation actions, as the current sampling methodology is inadequate.

Prevention of etomidate-induced myoclonus during anesthetic induction by pretreatment with dexmedetomidine.

Myoclonus induced by etomidate during induction of general anesthesia is undesirable. This study evaluated the effect of dexmedetomidine (DEX) pretreatment on the incidence and severity of etomidate-induced myoclonus. Ninety patients undergoing elective surgical procedures were randomly allocated to three groups (n=30 each) for intravenous administration of 10 mL isotonic saline (group I), 0.5 µg/kg DEX in 10 mL isotonic saline (group II), or 1.0 µg/kg DEX in 10 mL isotonic saline (group III) over 10 min. All groups subsequently received 0.3 mg/kg etomidate by intravenous push injection. The incidence and severity of myoclonus were recorded for 1 min after etomidate administration and the incidence of cardiovascular adverse events that occurred between the administration of the DEX infusion and 1 min after tracheal intubation was recorded. The incidence of myoclonus was significantly reduced in groups II and III (30.0 and 36.7%), compared with group I (63.3%). The incidence of severe sinus bradycardia was significantly increased in group III compared with group I (P<0.05), but there was no significant difference in heart rate in groups I and II. There were no significant differences in the incidence of low blood pressure among the 3 groups. Pretreatment with 0.5 and 1.0 µg/kg DEX significantly reduced the incidence of etomidate-induced myoclonus during anesthetic induction; however, 0.5 µg/kg DEX is recommended because it had fewer side effects.

Clofarabine in Combination with a Standard Remission Induction Regimen in Patients 18-60 Years Old with Previously Untreated Intermediate and Bad Risk Acute Myelogenous Leukemia (AML) or High Risk Myelodysplasia (MDS): Combined Phase I/II Results of the EORTC/Gimema AML-14A Trial

RW and FB are co-senior authors.Background: The prognosis of younger patients with intermediate/bad risk AML or high-risk MDS remains unsatisfactory. Although with current remission induction chemotherapy, 60-85% of patients achieves complete remission (CR), only 30-50% of them remains alive for more than 5 years. Clofarabine, a second-generation purine analog, is highly active as a single agent in AML. Willemze et al (Ann Hematol, 2014) recently reported the results of phase I of the AML-14A study and identified clofarabine at 10 mg/m2/day for 5 days as the maximum tolerated dose (given either in a 1-h infusion or as push injection) in combination with cytosine arabinoside (Ara-C) and idarubicin. We herein report the final results of the combined phase I and II parts of the AML-14A study that explored the antitumor activity of clofarabine containing induction combination regimens at the aforementioned phase I selected dosage schedules.Methods: Patients aged 18-60 years with intermediate/bad-risk AML or high-risk MDS (≥10% bone marrow blasts), adequate renal and hepatic function, and WBC count <100x109/L at baseline (short cytoreductive use of hydroxyurea was permitted if WBC count at diagnosis exceeded 100x109/l) were centrally randomized for remission induction chemotherapy (for 1 or 2 cycles) between 1-hr infusion (Arm A) or push injection (Arm B) of clofarabine administered at 10 mg/m2 on days 2, 4, 6, 8 and 10 in combination with Ara-C (100 mg/m2/day on days 1–10) and idarubicin (10 mg/m2/day, on days 1, 3, and 5). One cycle of consolidation including Ara-C (500 mg/m2 every 12 hrs on days 1-6) and idarubicin (10 mg/m2/day on days 4, 5 and 6) was administered in patients who achieved a CR/CRi in both arms. Primary endpoint was the CR/CRi rate after 1 or 2 cycles of induction. The aim was to determine whether in each treatment group the true CR/CRi rate is > 65% or not. Using a Fleming design, the regimen was considered active if ≥ 23 out of 30 patients per arm achieved CR/CRi. Secondary endpoints included safety, CR/CRi rate after consolidation, hematopoietic recovery, ability of CD34 harvesting after consolidation, disease-free survival (DFS) and survival from CR/CRi, and overall survival (OS). Randomization was stratified by institution and by presence of poor prognostic features (WBC at diagnosis >=100 x 109/L or very high-risk cytogenetics/FLT3-ITD).Results: A total of 64 patients was randomized: 12 in the phase I part and 52 in the phase II part of the study. Two patients did not meet the inclusion criteria and were excluded. Among the remaining 62 patients, 5 had high-risk MDS. Median age was 50 yrs (range 20-60). Baseline characteristics were well balanced between the two arms. The CR/CRi rate after induction was 84% (26 of 31 patients) in each arm (95% CI: 66-95%) (Table 1). In Arm A vs Arm B, the most frequent grade >2 non-hematological and non-infectious adverse events over the induction-consolidation period were anorexia (29% vs 32%), and diarrhea (26% vs 32%). Finally, during treatment period there were 2 toxic deaths in Arm-A and 1 in Arm-B.Table 1:Patient outcomes. Median follow-up was 1.8 (range, 1 – 5.25) yrs.Arm-A (n=31)Arm-B (n=31)CR/CRi after 1-2 courses of induction, # pts (%)23 (74) / 3 (10)25 (81) / 1 (3)CR/CRi after 1 course of induction, # pts (%)23 (74) / 3 (10)24 (77) / 1 (3)OS median (95%CI), yrs2.5 (1-NR)NROS at 1-yr (95%CI), %74 (55-86)74 (55-86)# of infectious episodes with G3-4 neutropenia / # of patients with infection episodes47 / 3059 / 31In patients who achieved CR/CRiTime to recovery from start of course 1# of days with neutrophils<0.5x109/L, median (range)28 (22-96)27 (20-50)# of days with neutrophils <1 x109/L, median (range)31 (22-99+)29 (21-50)# of days with platelets < 20x109/L, median (range)28 (24-83)27 (23-44)# of days with platelets < 100x109/L, median (range)31.5 (24-99+)31 (24-51)# of patients given allogeneic / autologous stem cell transplantation11/014/2DFS, median (95%CI), yrs1.5 (0.6-NR)NRDFS at 1-yr (95%CI), %58 (37-74)65 (44-80)relapse incidence at 1-yr (95%CI), %23 (7-39)19 (7-40)death in CR incidence at 1-yr (95%CI), %19 (4-34)15 (2-29)NR= not reached.Conclusions: The 2 tested clofarabine (5x10 mg/m2) containing regimens yielded an impressive (84%) CR/CRi rate among patients with intermediate/bad-risk AML and high-risk MDS patients. Toxicity profiles in the two arms appeared relatively comparable. DisclosuresOff Label Use: Clofarabine was used off label..

Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial)

This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56years) received 5days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10mg/m(2)/day, three at 15mg/m(2)/day; in arm B: one DLT at 15mg/m(2)/day). Three patients receiving 15mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92%) receiving clofarabine 10mg/m(2)/day; 10/13 (77%) receiving clofarabine 15mg/m(2)/day). Clofarabine, 5 × 10mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10mg/m(2)/day.

Ferric carboxymaltose injection: Iron replacement for IDA

than 3 million U.S. women of childbearing age affected due to conditions such as heavy uterine bleeding, postpartum anemia, and pregnancy. Previous drug therapies were limited to treating IDA in chronic kidney disease patients or required infusions over several hours or signifi cant multiple dosing sessions, whereas a single dose of up to 750 mg of ferric carboxymaltose can be administered undiluted as an I.V. push injection at a rate of 100 mg/min or as an I.V. infusion over at least 15 minutes.

The Impact of Field Data Acquisition Methodology Upon Prediction of Transport in the Made Aquifer

The hydraulic conductivity K of the aquifer of the MADE transport experiment, was measured in the past at a dense three-dimensional network of sampling stations. Two methodologies were employed: initially, the flowmeter (using numerous piezometers) and recently the DPIL (direct push injection logger) method. The results for the statistical moments of the lognormal K distribution were similar for the horizontal and vertical integral scales, but quite different for the geometric mean and the variance. By using our recently developed model of transport in highly heterogeneous formations we were able to predict the observed longitudinal mass distribution spreading and to compare with measurements. We found that prediction based on DPIL parameters led to agreement, while flowmeter data resulted in discrepancy. Using our transport model, we explore here in a systematic manner the impact of the different statistical parameters upon the breakthrough curve at different distances from the injection zone.

Performance of Full‐Scale Enhanced Reductive Dechlorination in Clay Till

At a low permeability clay till site contaminated with chlorinated ethenes (Gl. Kongevej, Denmark), enhanced reductive dechlorination (ERD) was applied by direct push injection of molasses and dechlorinating bacteria. The performance was investigated by long‐term groundwater monitoring, and after 4 years of remediation, the development of degradation in the clay till matrix was investigated by high‐resolution subsampling of intact cores. The formation of degradation products, the presence of specific degraders Dehalococcoides spp. with the vinyl chloride (VC) reductase gene vcrA, and the isotope fractionation of trichloroethene, cis‐dichloroethene (cis‐DCE), and VC showed that degradation of chlorinated ethenes occurred in the clay till matrix as well as in sand lenses, sand stringers, and fractures. Bioactive sections of up to 1.8 m had developed in the clay till matrix, but sections, where degradation was restricted to narrow zones around sand lenses and stringers, were also observed. After 4 years of remediation, an average mass reduction of 24% was estimated. Comparison of the results with model simulation scenarios indicate that a mass reduction of 85% can be obtained within approximately 50 years without further increase in the narrow reaction zones if no donor limitations occur at the site. Long‐term monitoring of the concentration of chlorinated ethenes in the underlying chalk aquifer revealed that the aquifer was affected by the more mobile degradation products cis‐DCE and VC generated during the remediation by ERD.