Assessing the role of patient support services on adherence rates in patients using glatiramer acetate for relapsing-remitting multiple sclerosis.

OBJECTIVE: To assess predictors of achievement of 80% Medication Possession Ratio (MPR) in patients receiving manufacturer-provided self-management services for relapsing-remitting multiple sclerosis (RRMS) patients taking glatiramer acetate (Copaxone). METHODS: De-identified patient records were selected for study inclusion if patients had been (1) continuously enrolled in one or more aspects of the self-management program for a minimum of 24 months and had adherence measured by MPR between the values of zero and one. Baseline patient univariate measures were assessed using chi-squared statistics for categorical variables and Analysis of Variance (ANOVA) for continuous variables. Bivariate logistic regression models were used to assess predictors of 80% MPR. RESULTS: A total of 5825 patients met the study inclusion criteria. About 70% of patients received manufacturer-provided injection training and 75% were eligible for, and utilized, copayment assistance; 74.3% of patients accessing sponsor provided support achieved a desired MPR of greater than or equal to 80%. Patients were 40% more likely to reach goal if injection training was provided by the manufacturer (OR = 1.435; 95% CI = 1.258-1.636) and were 30.6% more likely to achieve goal when eligible patients utilized copayment assistance programs (OR = 1.306; 95% CI = 1.109-1.570). Patients reinitiating treatment were at risk of lower adherence rates (OR = 0.605; CI = 0.476-0.769) compared to those who were new to therapy. CONCLUSIONS: Manufacturer-provided patient support programs improve adherence to glatiramer acetate therapy.

Automated determination of silicon isotope natural abundance by the acid decomposition of cesium hexafluosilicate.

A procedure for the automated determination of isotopic abundances of silicon from biogenic and lithogenic particulate matter and from dissolved silicon in fresh or saltwaters is reported. Samples are purified using proven procedures through the reaction of Si with acidified ammonium molybdate, followed by precipitation with triethylamine and combustion of the precipitate to yield silicon dioxide. The silicon dioxide is converted to cesium hexafluosilicate by dissolution in hydrogen fluoride and the addition of cesium chloride. Isotopic analysis is accomplished by decomposing the cesium hexafluosilicate with concentrated sulfuric acid to generate silicon tetrafluoride gas. Silicon tetrafluoride is purified cryogenically and analyzed on a gas source isotope ratio mass spectrometer. Yields of silicon tetrafluoride are >99.5%. The procedure can be automated by modifying commercial inlet systems designed for carbonate analysis. The procedure is free of memory effects and isotopic biases. Reproducibility is +/-0.03-0.10 per thousand for a variety of natural and synthetic materials.

Quadriphasic waveforms are superior to triphasic waveforms for transthoracic defibrillation in a cardiac arrest swine model with high impedance.

BACKGROUND: We have demonstrated previously that triphasic waveform shocks were superior to biphasic waveform shocks for transthoracic defibrillation. Our purpose was to compare the efficacy and safety of quadriphasic versus triphasic shocks for transthoracic defibrillation in a porcine model. METHODS: Sixteen adult swine (19-25 kg, mean: 21.5 kg) were deeply anesthetized and intubated. To simulate impedance of the human chest, fixed electrical resistors (25 or 50 ohms) was placed in series with the defibrillator and the chest of each pig. After 30 s of electrically induced VF, each pig received transthoracic shocks, using either a truncated exponential triphasic waveform (5 ms positive pulse duration, 5 ms negative pulse duration and 5 ms positive pulse duration, total waveform duration 15 ms) or a quadriphasic waveform (5/5/5/5 ms, total waveform duration 20 ms). Each pig received transthoracic triphasic and quadriphasic shocks at three selected energy levels (50, 100 and 150 J) in random sequence. Four shocks were delivered at each energy level to construct an energy versus % success curve. Success was defined as VF termination at 5 s after shock. The total shocks were divided into three groups based on the delivered energy actually delivered to the animal: <40, 40-65 and >65 J. Delivered energy = (animal impedance/total impedance) times selected energy of the shock. RESULTS: For high-impedance animals (86-102 ohms), quadriphasic waveform shocks achieved significantly higher percent shock success than triphasic shocks for the termination of VF at the energy levels of >65 J actually delivered (quadriphasic 72.7+/-12.2%, triphasic 38.9+/-7.7%, p<0.02). No differences in the shock success between quadriphasic and triphasic waveforms were found for other two energy levels. There were no differences in ventricular tachycardia or asystole after shocks between quadriphasic and triphasic waveforms. CONCLUSION: In this porcine model, 20 ms (5/5/5/5) quadriphasic shocks were superior to 15 ms (5/5/5) triphasic shocks for transthoracic defibrillation in animals with impedances that simulated high impedance in humans.

Immediate termination of fibrillation at 50% probability of overall success correlates with defibrillation dose-response curve width.

INTRODUCTION: Issues in transthoracic defibrillation, including waveform shape, fixed versus escalating dose protocol, and low- versus high-energy shocks, can be addressed by examining the defibrillation dose-response curve. We tested the hypothesis that, for commonly used defibrillation waveforms, the steepness of the overall defibrillation dose-response curve, measured as normalized curve width, correlates with the probability of a successful defibrillation being immediate at the shock intensity producing 50% success. METHODS AND RESULTS: We used 16 isolated rabbit hearts to determine probability of overall success as a function of shock intensity and probability that a successful defibrillation is immediate rather than progressive (followed by several extrasystoles) at the shock intensity producing 50% overall defibrillation success. Two waveform pairs were tested--a monophasic damped sine versus a biphasic truncated exponential waveform commonly used for transthoracic defibrillation, and a monophasic/biphasic truncated exponential waveform pair similar to those used in internal cardioverter defibrillators. There was a close correlation between probability of a successful defibrillation being immediate at 150 and normalized curve width for the defibrillation dose-response curve. CONCLUSION: Our findings suggest that a high probability of successful defibrillation being immediate at low shock intensities is correlated with a narrow normalized curve width for the defibrillation dose-response curve.

Surgical open-chest ventricular defibrillation: triphasic waveforms are superior to biphasic waveforms.

Triphasic shocks have been evaluated for endocardial defibrillation but not for open-chest epicardial defibrillation. The purpose of this study was to compare the efficacy and safety of biphasic versus triphasic shocks for epicardial defibrillation in a porcine model. Twenty-two adult swine (18-28 kg) were deeply anesthetized and intubated. After 30 seconds electrically induced VF, each pig received truncated exponential biphasic (7.2-ms positive pulse duration and 7.2-ms negative pulse duration, total waveform duration 14.4 ms) and triphasic (4.8/4.8/4.8 ms, total waveform duration 14.4 ms) epicardial shocks. Pigs in group 1 (n = 11) received epicardial biphasic and triphasic shocks from large hand held paddle electrodes (44.2 cm2); pigs in group 2 (n = 11) received shocks from small paddle electrodes (15.9 cm2). Shocks were given at five selected energy levels (3-30 J) in random sequence. Four shocks were delivered at each energy level to construct an energy versus percentage of success curve. In group 1 (large paddle electrodes), percentage of shock success was significantly higher for triphasic shocks at the energy levels of 3, 5, 10, and 20 J compared to biphasic shocks. In group 2 (small paddle electrodes), triphasic shocks yielded a significantly higher percentage of shock success than biphasic shocks at the energy levels of 5, 10, and 20 J). Shock induced ventricular tachycardia was similar for both waveforms; asystole was rare. For open-chest defibrillation, triphasic waveform shocks were superior to biphasic waveform shocks for VF termination at energy levels of 3-20 J and were as safe as biphasic shocks.

Southern Ocean iron enrichment experiment: carbon cycling in high- and low-Si waters.

The availability of iron is known to exert a controlling influence on biological productivity in surface waters over large areas of the ocean and may have been an important factor in the variation of the concentration of atmospheric carbon dioxide over glacial cycles. The effect of iron in the Southern Ocean is particularly important because of its large area and abundant nitrate, yet iron-enhanced growth of phytoplankton may be differentially expressed between waters with high silicic acid in the south and low silicic acid in the north, where diatom growth may be limited by both silicic acid and iron. Two mesoscale experiments, designed to investigate the effects of iron enrichment in regions with high and low concentrations of silicic acid, were performed in the Southern Ocean. These experiments demonstrate iron's pivotal role in controlling carbon uptake and regulating atmospheric partial pressure of carbon dioxide.

Triphasic waveforms are superior to biphasic waveforms for transthoracic defibrillation: experimental studies.

OBJECTIVES: Our objective was to evaluate the efficacy of triphasic waveforms for transthoracic defibrillation in a swine model. BACKGROUND: Triphasic shocks have been found to cause less post-shock dysfunction than biphasic shocks in chick embryo studies. METHODS: After 30 s of electrically induced ventricular fibrillation (VF), each pig in part I (n = 32) received truncated exponential biphasic (7.2/7.2 ms) and triphasic (4.8/4.8/4.8 ms) transthoracic shocks. Each pig in part II (n = 14) received biphasic (5/5 ms) and triphasic shocks (5/5/5 ms). Three selected energy levels (50, 100, and 150 J) were tested for parts I and II. Pigs in part III (n = 13) received biphasic (5/5 ms) and triphasic (5/5/5 ms) shocks at a higher energy (200 and 300 J). Although the individual pulse durations of these shocks were equal, the energy of each pulse varied. Nine pigs in part I also received shocks where each individual pulse contained equal energy but was of a different duration (biphasic 3.3/11.1 ms; triphasic 2.0/3.2/9.2 ms). RESULTS: Triphasic shocks of equal duration pulses achieved higher success than biphasic shocks at delivered low energies: <40 J: 38 +/- 5% triphasic vs. 19 +/- 4% biphasic (p < 0.01); 40 to <50 J: 66 +/- 7% vs. 42 +/- 7% (p < 0.01); and 50 to <65 J: 78 +/- 4% vs. 54 +/- 5% (p < 0.05). Shocks of equal energy but different duration pulses achieved relatively poor success for both triphasic and biphasic waveforms. Shock-induced ventricular tachycardia (VT) and asystole occurred less often after triphasic shocks. CONCLUSIONS: Triphasic transthoracic shocks composed of equal duration pulses were superior to biphasic shocks for VF termination at low energies and caused less VT and asystole.

Open-chest epicardial "surgical" defibrillation: biphasic versus monophasic waveform shocks.

The aim of the study was to compare biphasic versus monophasic shocks for open-chest epicardial defibrillation. Transthoracic biphasic waveform shocks require less energy to terminate ventricular fibrillation compared to monophasic waveform shocks. However, if biphasic shocks are effective for open-chest epicardial ("surgical") defibrillation has not been established. Twenty-eight anesthetized adult swine (15-25 kg) underwent a midline sternotomy. Ventricular fibrillation was electrically induced. After 15 seconds of ventricular fibrillation, each pig in group 1 (n = 16) randomly received damped sinusoidal monophasic epicardial shocks and truncated exponential biphasic epicardial shocks from large (44.2 cm2) paddle electrodes at eight energy levels (2-50 J). Pigs in group 2 (n = 12) received monophasic and truncated exponential biphasic shocks from small (15.9 cm2) paddle electrodes. In group 1 (large paddle electrodes), the overall percent shock success rose from 15 +/- 9% at 2 J to 97 +/- 3% at 50 J. In this group there was no significant difference in percent of shock success between damped sinusoidal monophasic and biphasic waveform shocks. In group 2 (small paddle electrodes), biphasic shocks yielded a significantly higher percent of shock success than monophasic shocks at mid-energy levels from 7 to 20 J (all P < 0.01). With small surgical paddle electrodes, biphasic waveform shocks demonstrated a significantly higher percent of shock success rate compared to monophasic waveform shocks. With large paddle electrodes, the two waveforms were equally effective.