Conventional IV Research Articles

Anticipation, Tax Avoidance, and the Price Elasticity of Gasoline Demand

Traditional least squares estimates of the responsiveness of gasoline consumption to changes in gasoline prices are biased toward zero, given the endogeneity of gasoline prices. A seemingly natural solution to this problem is to instrument for gasoline prices using gasoline taxes, but this approach tends to yield implausibly large price elasticities. We demonstrate that anticipatory behavior provides an important explanation for this result. We provide evidence that gasoline buyers increase gasoline purchases before tax increases and delay gasoline purchases before tax decreases. This intertemporal substitution renders the tax instrument endogenous, invalidating conventional IV analysis. We show that including suitable leads and lags in the regression restores the validity of the IV estimator, resulting in much lower and more plausible elasticity estimates. Our analysis has implications more broadly for the IV analysis of markets in which buyers may store purchases for future consumption.

Anticipation, Tax Avoidance, and the Price Elasticity of Gasoline Demand

Traditional least squares estimates of the responsiveness of gasoline consumption to changes in gasoline prices are biased toward zero, given the endogeneity of gasoline prices. A seemingly natural solution to this problem is to instrument for gasoline prices using gasoline taxes, but this approach tends to yield implausibly large price elasticities. We demonstrate that anticipatory behavior provides an important explanation for this result. We provide evidence that gasoline buyers increase gasoline purchases before tax increases and delay gasoline purchases before tax decreases. This intertemporal substitution renders the tax instrument endogenous, invalidating conventional IV analysis. We show that including suitable leads and lags in the regression restores the validity of the IV estimator, resulting in much lower and more plausible elasticity estimates. Our analysis has implications more broadly for the IV analysis of markets in which buyers may store purchases for future consumption.

Effectiveness of Adjunctive Inhaled Colistin in Treatment of Ventilator Associated Pneumonia

Ventilator-Associated pneumonia (VAP) represents a major health problem in mechanically ventilated patients in intensive care units (ICUs). Aerosolized colistin could represent an adjunctive treatment to intravenous antibiotics in VAP. To evaluate the safety and efficacy of adjunctive inhaled colistin in treatment of patients with Gram-negative VAP compared to the conventional intravenous antibiotic regimen alone. This prospective randomized controlled study was conducted from July 2013 to August 2014 at Kasr El-Aini Medical ICU. Our study included a total number of 50 cases with VAP randomly assigned into two equal groups; a study group (who received the conventional systemic IV antibiotic regimen plus adjunctive inhaled colistin) and a control group (who received the conventional systemic IV antibiotic regimen alone). 76% of the patients were men with severe underlying co-morbidities. The main causative organisms of VAP were Klebsiella spp. (32%), Acinetobacter spp. (26%) and Pseudomonas spp. (24%). Patients in the study group had significantly more favourable microbiological outcome when compared with patients in the control group (80% versus 52%, P=0.03). No adverse effects related to inhaled colistin (nephrotoxicity, neurotoxicity, bronchoconstriction, cough, apnea or chest tightness) were recorded. Inhaled colistin seems to be safe and efficient as an adjunctive treatment for patients with Gram-negative VAP.

Abstract No. 4: High resolution quantitative MRI-guided nano-embolization enhances drug delivery to liver tumors

There is a critical unmet need to monitor intratumoral drug uptake non-invasively. Superparamagnetic iron oxide nanoparticles (SPIOs) are agents with dual diagnostic and therapeutic properties that may meet this need. However, systemic (IV) administration results in unfavorable biodistribution with minimal tumor delivery. To overcome this limitation we propose nano-embolization (NE) as the image-guided delivery of SPIOs and embolic agents directly into the blood supply of tumors. It remains unknown if MRI can quantify the amount of NPs delivered to tumors during NE. Using VX2 liver tumors, we tested the hypotheses that a) NE increases uptake of therapeutic SPIOs over IV administration and b) 7T MRI can quantify intratumoral drug delivery. We induced VX2 liver tumors in 20 rabbits, evenly dividing them into NE and control (IV) groups. Both groups received doxorubicin-loaded therapeutic SPIOs at 0.56 mg/kg body weight. For the NE group, SPIOs and ethiodol were delivered into the hepatic artery under fluoroscopy. T2*-weighted gradient echo imaging (Bruker 7T ClinScan MRI) was performed on both groups pre and post-treatment to quantify SPIO delivery and uptake using T2*W mapping. After necropsy, we used ICP-MS as the gold standard to measure SPIO concentrations in normal liver and tumor pathological specimens. We compared SPIO uptake between the groups using ANOVA with post-hoc Tukey analysis, with p<0.05 considered significant. NE significantly increased tumor SPIO uptake 240% over IV delivery alone (340 vs. 140 μg Fe/mg, p<0.05). This correlated with T2*W MRI, which showed a significant T2 signal drop in NE tumors over controls (ΔT2: 47.4 ms vs. 18.9 ms, p<0.05). Furthermore, NE resulted in 75% less off target delivery to healthy liver tissue than IV delivery (p<0.05). NE improves tumor uptake of therapeutic SPIOs over conventional IV administration, with significantly less off-target delivery. 7T MRI can also quantify SPIO uptake non-invasively. To determine the optimal dose of therapeutic nanoparticles to inject, future studies should correlate SPIO delivery with tumor response.

Estimating Decision-Relevant Comparative Effects Using Instrumental Variables

Instrumental variables methods (IV) are widely used in the health economics literature to adjust for hidden selection biases in observational studies when estimating treatment effects. Less attention has been paid in the applied literature to the proper use of IVs if treatment effects are heterogeneous across subjects. Such a heterogeneity in effects becomes an issue for IV estimators when individuals' self-selected choices of treatments are correlated with expected idiosyncratic gains or losses from treatments. We present an overview of the challenges that arise with IV estimators in the presence of effect heterogeneity and self-selection and compare conventional IV analysis with alternative approaches that use IVs to directly address these challenges. Using a Medicare sample of clinically localized breast cancer patients, we study the impact of breast-conserving surgery and radiation with mastectomy on 3-year survival rates. Our results reveal the traditional IV results may have masked important heterogeneity in treatment effects. In the context of these results, we discuss the advantages and limitations of conventional and alternative IV methods in estimating mean treatment-effect parameters, the role of heterogeneity in comparative effectiveness research and the implications for diffusion of technology.

Comparison of Continuous and Intermittent IV Infusion of Vancomycin: Systematic Review

There is some evidence that administration of vancomycin by continuous infusion has pharmacokinetic and pharmacodynamic advantages over traditional intermittent dosing. Whether these advantages translate into clinical efficacy remains controversial. To review the literature comparing continuous infusion of vancomycin and conventional intermittent IV dosing in terms of efficacy and safety. A literature search was conducted in the PubMed/MEDLINE and Embase databases and the Cochrane Central Register of Controlled Trials, and by means of the Google search engine, and the reference lists of pertinent articles were searched manually. All human studies published in English or French that evaluated vancomycin given by continuous and intermittent IV infusion were reviewed. Articles that did not include a comparator arm and those that assessed continuous and intermittent intraperitoneal infusions were excluded. The level of evidence of each study was categorized according to the US Preventive Services Task Force rating scale. In total, 9 studies were identified: 1 in a pediatric population and 8 in adult populations. Of the 3 studies with the highest quality of evidence (level I), one demonstrated pharmacodynamic advantages with continuous infusion of vancomycin. Of the 6 studies representing a moderate level of evidence (level II), 3 also favoured continuous infusion in terms of pharmacokinetic and pharmacodynamic outcomes, but the findings in terms of clinical outcomes were mixed. Current evidence evaluating the pharmacokinetic and pharmacodynamic advantages and clinical efficacy of continuous versus intermittent vancomycin infusions is inconsistent and does not support the routine use of continuous infusion for the treatment of multidrug-resistant gram-positive infections.

Sequential antibiotic therapy in the treatment of hospitalized children with community-acquired pneumonia

Objective: Evaluate the efficacy, time and the cost of hospitalization using sequential therapy (short IV course + oral antibiotics) in hospitalized children with community acquire bacterial pneumonia without pleural effusion and compared to conventional IV therapy. Methods: Prospective, randomized, open trial, admitting patients with community acquire bacterial pneumonia that fulfilled all the following criteria: (1) Toxemia; (2) Fever 38°C; (3) Abnormal physical exam; (4) Blood leukocytes >15,000); (5) PCR 48mg/l; (6) Chest X-Ray compatible with bacterial infection. Patients were excluded if they had wheezing on chest auscultation or had any associated systemic disease. On admission, patient severity was documented by Pediatric Risk of Mortality score (PRISM). Patients were randomized to conventional treatment (group C) or sequential treatment (group S). Children 3 month to six years old received intravenous ampycillin and those older than six years intravenous penicillin G. Patients in group C received IV therapy for 10 days or after 24 hours without fever. In group S, oral replaced IV antibiotic when at least three out of six clinical admission criteria improved. Results: 258 patients were analyzed, 130 of then (50.4%) in group C and 128 (49.6%) in group S. There was no difference between both groups, in relation of age, sex, onset of symptoms, (PRISM) score, and previous use of ATB. The time of IV ATB was significantly shorter in group S (3 versus 4 days; p < 0,001) There was a direct correlation with PRISM score and number of days hospitalized. Time of hospitalization were significantly decreased in group S (5 versus 6 days p < 0.01) with hospital cost 19.7% lower when compared with group C (p < 0,02). There was no difference in treatment failure between the two groups (p = 0.48). Conclusion: Our study suggests that bacterial pneumonia treatment using oral sequential ATB is safe and effective when compare with prolonged IV antibiotic treatment, with shorter hospitalization time and lower cost.

Comparative study between conventional macroscopic IV techniques and advanced AFM based methods for electrical characterization of dielectrics at the nanoscale

High-k dielectrics exhibit strong variations in their electrical characteristics on the nanometer scale due to morphology alteration. Therefore, electrical measurement techniques with nanometer resolution based on atomic force microscopy (AFM) like conductive AFM (cAFM) and tunneling AFM (TUNA) are essentially very well applicable to complement conventional macroscopic current–voltage ( IV) techniques. Comparative experiments between conventional IV, cAFM and TUNA measurements on SiO 2 films and on high-k/SiO 2 stacks prove the capability and the accuracy of cAFM/TUNA as advanced methods for electrical characterization of thin dielectric films. Especially TUNA provides the spatial resolution and the current sensitivity required for the characterization of local electrical properties at the nanoscale allowing for the characterization of dielectric layers at high current densities.

Design and development of multivesicular liposomal depot delivery system for controlled systemic delivery of acyclovir sodium

The aim of the present study was to design a depot delivery system of acyclovir sodium using multivesicular liposomes (MVLs) to overcome the limitations of conventional therapies and to investigate its in vivo effectiveness for sustained delivery. MVLs of acyclovir were prepared by the reverse phase evaporation method. The loading efficiency of the MVLs (45%-82%) was found to be 3 to 6 times higher than conventional multilamellar vesicles (MLVs). The in vitro release of acyclovir from MVL formulations was found to be in a sustained manner and only 70% of drug was released in 96 hours, whereas conventional MLVs released 80% of drug in 16 hours. Following intradermal administration to Wistar rats, the MVL formulations showed effective plasma concentration for 48 hours compared with MLVs and free drug solution (12-16 hours). C(max) values of MVL formulations were significantly less (8.6-11.4 microg/mL) than MLV and free drug solution (12.5 microg/mL). The AUC(0-48) of the MVL formulations was 1.5- and 3-fold higher compared with conventional liposomes and free drug solution, respectively. Overall, formulations containing phosphatidyl glycerol as negatively charged lipid showed better results. The MVL delivery system as an intradermal depot offers the advantage of a very high loading and controlled release of acyclovir for an extended period of time. The increase in AUC and decrease in C(max) reflects that the MVL formulations could reduce the toxic complications and limitations of conventional iv and oral therapies.

465 Infusional chemotherapy by implantable subcutaneous pump: Study in multimetastatic kidney cancer

65 patients with multimetastatic kidney cancer were treated by continuous infusional chemotherapy using a totally subcutaneous implantable pump. They were given from 8 to 78 fortnight cycles of fluorodeoxyuri-dine (FUDR) at doses ranging from 0.15 to 0.30 mg/kg/day. The sites of metastases were: lungs, liver, bone, lymph nodes, brain; moreover some patients had a contralateral kidney cancer or a recurrent disease at the site of the previous nephrectomy. The response rate was comparable to that of conventional iv chemotherapy, but to its comparison we obtained a dramatic decrease in side effects (6.1% anemia, 4.6% mucositis, 3% hepatitis-nausea-diarrhea). The infusional therapy is now being studied in a protocol including patients who were excluded from the IL-2/IFN protocol or showed a progressive disease during it.

Efficacy of large-bore intravenous fluid administration sets designed for rapid volume resuscitation

We tested the hypothesis that large-bore iv tubing sets provide greater in vitro flow rates than conventional sets currently utilized for the administration of normal saline. The study was conducted in two parts. First, flow rates were measured using a conventional iv tubing set under gravity and 300 mm Hg of pressure, and four large-bore iv tubing sets under gravity. Additional measurements were made after attaching various catheters and sheaths ranging in size from 14 ga to 9 Fr. Five trials were conducted for each combination. Second, we measured the amount of time taken in a mock drill by 28 randomly chosen anesthesiology residents and staff to load a unit of packed RBC into a pressure infusor bag, inflate to 300 mm Hg, and deflate to ambient pressure. Data were analyzed for individual tubing sets as a whole and individual catheter-tubing set combinations, using the Mann-Whitney U test with Bonferroni adjustment. Statistically significant (p less than .03) differences in flow rates were noted between the conventional set under gravity compared with both the pressurized conventional set and the large-bore tubing sets under gravity. There was no statistical difference in flow rates between pressurized conventional iv sets and large-bore iv sets. Mean time necessary for the 28 anesthesiology staff and residents to pressurize and deflate a conventional tubing set was 65 sec/bag of packed RBC. We conclude that a considerable amount of time can be saved by utilizing large-bore iv tubing sets instead of conventional pressurized sets during massive volume resuscitation. Clinical trials are indicated to corroborate these results.

Endobronchial instillation of epinephrine during cardiopulmonary resuscitation.

We used a standard animal CPR model to study the effectiveness and hemodynamic response of 100 micrograms/kg epinephrine administered endobronchially and to compare the findings after conventional iv administration. Results showed that the endobronchial and iv epinephrine medication improved the survival rate by 100% compared to that of a control group receiving no medication. Although the hemodynamic conditions during cardiac compression were not significantly different after both routes of drug administration, endobronchial instillation produced a prolonged drug action during the first hour of restored spontaneous circulation. A more extensive use of this type of drug administration, especially in out-of-hospital resuscitation, is suggested.