Market share and costs of biologic therapies for inflammatory bowel disease in the USA.

BACKGROUND: Real-world data quantifying the costs of increasing use of biologics in inflammatory bowel disease (IBD) are unknown. AIM: To determine the outpatient IBD drug utilization trends, relative market share, and costs in the USA during a 9-year period. METHODS: The Truven MarketScan® Database was analysed for patients with Crohn's disease (CD) and ulcerative colitis (UC) during 2007-2015. National drug codes were used to identify prescription drugs; Healthcare Common Procedure Coding System J-codes were used to capture biologic out-patient infusions. Proportion of drug usage, relative market share and per-member per-year (PMPY) costs were analysed for biologics, immunomodulators, 5-ASAs and corticosteroids. RESULTS: In 415 405 patients (188 842 CD; 195 183 UC; 31 380 indeterminate colitis; 54.67% female), utilization trends show a consistent rise in the market share of biologics during the 9-year study period. The proportion of patients using biologics increased from 21.8% to 43.8% for CD and 5.1%-16.2% for UC. This contrasts a small decrease in immunomodulator and 5-ASA use for CD and relative constancy of other classes including corticosteroids-only use as primary IBD medication from 2007 to 2015. The average biologic-taking patient accounted for $25 275 PMPY in 2007 and $36 051 PMPY in 2015. The average paediatric biologic-taking patient accounted for $23 616 PMPY in 2007 and $41 109 PMPY in 2015. In all patients, the share of costs for biologics increased from 72.9% in 2007 to 85.7% in 2015 (81.7% in 2007 to 94.9% in 2015 in paediatrics). CONCLUSION: The vast majority of costs allocated to out-patient IBD medications in the USA is attributed to increasing use of biologic therapies despite the relative minority of biologic-taking patients.

Innervation zone shift with changes in joint angle in the brachial biceps.

Empirical evidence is presented suggesting that the innervation zone of the brachial biceps shifts relative to recording electrodes with changes in joint angle. Myoelectric signal data were acquired from five subjects using a 16-channel linear electrode array, and analyzed to determine a reversal in signal propagation direction indicating innervation zone location. An analysis of the effect of joint angle changes on innervation zone location yielded statistically significant results (ANOVA, alpha = 0.05, p < 0.001) suggesting that the innervation zone moves between 5 and 30 mm in a direction distal to the shoulder as the arm is extended, statistically independent of force level (ANOVA, alpha = 0.05, p > 0.2).

Interleukin 6 differentially potentiates the antitumor effects of taxol and vinblastine in U266 human myeloma cells.

Newer therapeutic strategies for the treatment of multiple myeloma have focused on antagonizing the growth-promoting functions of interleukin 6 (IL-6). In this study, we examined the antitumor effects of two mechanistically different microtubule poisons, Taxol and vinblastine, in U266 human myeloma cells and determined whether IL-6 altered these effects. Taxol and vinblastine led to a dose-dependent inhibition of [3H]thymidine incorporation and altered the DNA distribution pattern of U266 cells. Both drugs led to an increase in the proportion of cells in the sub-G1 fraction (<2N DNA). However, at the IC50 concentration, vinblastine, but not Taxol, increased the percentage of cells in the G2-M phase of the cell cycle. In the presence of IL-6, the DNA distribution pattern induced by Taxol or vinblastine was altered. Whereas IL-6 augmented the sub-G1 fraction and G2-M phase for Taxol-treated cells, only the G2-M phase was increased for vinblastine-treated cells. Furthermore, IL-6 enhanced the cytotoxicity of both drugs, which became evident only during recovery in cytokine-free and drug-free medium. However, the cytotoxicity of Taxol was augmented to a significantly greater extent than that of vinblastine (P < 0.001). Immunostaining with antibodies to alpha-tubulin and mitogen-activated protein kinase revealed colocalization of these two proteins within microtubule asters. In the presence of IL-6, the number of cells containing microtubule asters increased for Taxol treatment, but not for vinblastine treatment. These data indicate that IL-6 leads to differential modulation of the cytotoxicity of Taxol and vinblastine in U266 cells. Whereas recruitment of cells in the S phase of the cell cycle represents a major mechanism by which IL-6 potentiates the cytotoxicity of vinblastine, augmentation of the cytotoxicity of Taxol involves additional mechanisms. Furthermore, our data suggest that the microtubule-associated form of mitogen-activated protein kinase may play a role in IL-6-mediated enhancement of the cytotoxicity of Taxol. The clinical implications of these findings are discussed.

The short-time Fourier transform and muscle fatigue assessment in dynamic contractions.

The mean frequency of the power spectrum of an electromyographic signal is an accepted index for monitoring fatigue in static contractions. There is however, indication that it may be a useful index even in dynamic contractions in which muscle length and/or force may vary. The objective of this investigation was to explore this possibility. An examination of the effects of amplitude modulation on modeled electromyographic signals revealed that changes in variance created in this way do not sufficiently affect characteristic frequency data to obscure a trend with fatigue. This validated the contention that not all non-stationarities in signals necessarily manifest in power spectral parameters. While an investigation of the nature and effects of non-stationarities in real electromyographic signals produced from dynamic contractions indicated that a more complex model is warranted, the results also indicated that averaging associated with estimating spectral parameters with the short-time Fourier transform can control the effects of the more complex non-stationarities. Finally, a fatigue test involving dynamic contractions at a force level under 30% of peak voluntary dynamic range, validated that it was possible to track fatigue in dynamic contractions using a traditional short-time Fourier transform methodology.

Non-stationary myoelectric signals and muscle fatigue.

A mathematical derivation for the mean frequency of a myoelectric signal (MES) is provided based on an amplitude modulation model for non-stationary MES. With this derivation, it is shown that mean frequency estimates of stationary and non-stationary myoelectric signals theoretically are not significantly different in a physiologically practical context. While this prediction is confirmed via a computer simulation, it is refuted with empirical evidence. Regardless, it is shown in a final study that mean frequency is capable of tracking a downward shift in the power spectrum with fatigue even in non-stationary myoelectric signals.

CleanEMG--power line interference estimation in sEMG using an adaptive least squares algorithm.

This paper presents an adaptive least squares algorithm for estimating the power line interference in surface electromyography (sEMG) signals. The algorithm estimates the power line interference, without the need for a reference input. Power line interference can be removed by subtracting the estimate from the original sEMG signal. The algorithm is evaluated with simulated sEMG based on its ability to accurately estimate power line interference at different frequencies and at various signal-to-noise ratios. Power line estimates produced by the algorithm are accurate for signal-to-noise ratios below 15 dB (SNR estimation error at 15 dB is 14.7995 dB + 1.6547 dB).

Managing the implementation of a pharmacy information system.

The stages by which a pharmacy information system should be implemented are described. Implementation can be divided into three stages. The first stage is preimplementation, during which the hardware vendor installs and configures the operating system, the software is installed, the site is prepared, files are built, policies and procedures are modified or written, staff members are trained, functions or programs are tested, and supplies are purchased. The second stage is implementation, in which the new system becomes operational and is expanded. There are four basic implementation strategies: abrupt switchover, parallel conversion, conversion of one location at a time, and conversion of functions or modules in stages. The final stage is postimplementation, which consists of testing of the system, acceptance or rejection of the system, and the institution of quality control procedures. The acceptance criteria should be developed before the system is purchased. It is important to involve the pharmacy staff and other hospital departments in the planning for an information system. Careful management before, during, and after the implementation of a new pharmacy information system is essential to a smooth and timely conversion.

Purification and properties of Escherichia coli dimethyl sulfoxide reductase, an iron-sulfur molybdoenzyme with broad substrate specificity.

Dimethyl sulfoxide reductase, a terminal electron transfer enzyme, was purified from anaerobically grown Escherichia coli harboring a plasmid which codes for dimethyl sulfoxide reductase. The enzyme was purified to greater than 90% homogeneity from cell envelopes by a three-step purification procedure involving extraction with the detergent Triton X-100, chromatofocusing, and DEAE ion-exchange chromatography. The purified enzyme was composed of three subunits with molecular weights of 82,600, 23,600, and 22,700 as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native molecular weight was determined by gel electrophoresis to be 155,000. The purified enzyme contained 7.5 atoms of iron and 0.34 atom of molybdenum per mol of enzyme. The presence of molybdopterin cofactor in dimethyl sulfoxide reductase was identified by reconstitution of cofactor-deficient NADPH nitrate reductase activity from Neurospora crassa nit-I mutant and by UV absorption and fluorescence emission spectra. The enzyme displayed a very broad substrate specificity, reducing various N-oxide and sulfoxide compounds as well as chlorate and hydroxylamine.

Short-term comparative outcomes associated with the use of GP IIb/IIIa antagonists in patients undergoing coronary intervention.

BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists reduce the occurrence of death, myocardial infarction (MI) and urgent revascularization among patients undergoing percutaneous coronary intervention (PCI). Despite a similar mechanism of platelet inhibition, the three currently approved agents vary widely in cost. PURPOSE: The purpose of this prospectively designed, retrospective analysis was to determine clinical outcomes for patients receiving abciximab, tirofiban or eptifibatide as adjunctive therapy during PCI at a single center. We hypothesized that there would be no difference in outcomes during hospitalization following PCI in patients receiving tirofiban or eptifibatide compared with those patients who received abciximab. Outcomes examined included in-hospital mortality, hemorrhagic procedural complications, need for recatheterization, peak creatine kinase following intervention and length of hospital stay (LOS). RESULTS: Two hundred and sixty seven consecutive patients in whom GP IIb/IIIa antagonist therapy was initiated in the catheterization laboratory for PCI were analyzed. Abciximab-treated patients were more likely to be undergoing primary (p<0.001) and rescue (p=0.022) PCI and to have received fibrinolytic therapy (p=0.013) when compared to patients receiving tirofiban or eptifibatide. There were no significant differences between abciximab- and non abciximab-treated patients in either the primary PCI or non primary PCI groups in any of the studied endpoints. In patients undergoing primary PCI, abciximab-treated patients when compared with non abciximab-treated patients exhibited a trend toward an increase in hospital LOS (7.8+/-7.0 d vs 6.2+/-3.9, p=0.19) and in the frequency of hemorrhagic complications (22.1% vs 5.3%, p=0.11). In patients not receiving fibrinolytic therapy, abciximab-treated patients experienced a trend toward increased hemorrhagic complications following PCI when compared to non abciximab-treated patients (10.2% vs 6.0%, p=0.28). Complications distant from the vascular access site comprised 62.5% of hemorrhagic complications in the abciximab-treated group, but only 20% of the complications in the non-abciximab treated population (p<0.001). These data suggest no differences in acute outcomes between groups of patients receiving abciximab or other approved GP IIb/IIIa antagonists highlighting a potential significant cost saving. These data will require interpretation following the publication of comparative trials.