A Systematic Evaluation of Cost-Saving Dosing Regimens for Therapeutic Antibodies and Antibody-Drug Conjugates for the Treatment of Lung Cancer

Background: Expensive novel anticancer drugs put a serious strain on healthcare budgets, and the associated drug expenses limit access to life-saving treatments worldwide. Objective: We aimed to develop alternative dosing regimens to reduce drug expenses. Methods: We developed alternative dosing regimens for the following monoclonal antibodies used for the treatment of lung cancer: amivantamab, atezolizumab, bevacizumab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and ramucirumab; and for the antibody-drug conjugate trastuzumab deruxtecan. The alternative dosing regimens were developed by means of modeling and simulation based on the population pharmacokinetic models developed by the license holders. They were based on weight bands and the administration of complete vials to limit drug wastage. The resulting dosing regimens were developed to comply with criteria used by regulatory authorities for in silico dose development. Results: We found that alternative dosing regimens could result in cost savings that range from 11 to 28%, and lead to equivalent pharmacokinetic exposure with no relevant increases in variability in exposure. Conclusions: Dosing regimens based on weight bands and the use of complete vials to reduce drug wastage result in less expenses while maintaining equivalent exposure. The level of evidence of our proposal is the same as accepted by regulatory authorities for the approval of alternative dosing regimens of other monoclonal antibodies in oncology. The proposed alternative dosing regimens can, therefore, be directly implemented in clinical practice.</p

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

EXPERIMENTAL STUDY OF THE ULTRASONIC FIELD SCATTERED FROM AN IMMERSED ELASTIC WEDGE

In this paper we investigate the interaction of a bounded acoustic beam incident on a 90° wedge shaped sample immersed in a fluid (water). The variations of the amplitude of the signal radiated by the tip of the wedge in a plane perpendicular to the edge are recorded against the scattering angle and plotted in polar diagrams. The influence of different parameters such as the frequency and the angle of incidence on the experimental results are more specifically investigated. Some of the data are compared to optical experiments using a pulsed schlieren technique

Canonical correspondence analysis and related multivariate methods in aquatic ecology

Canonical correspondence analysis (CCA) is a multivariate method to elucidate the relationships between biological assemblages of species and their environment. The method is designed to extract synthetic environmental gradients from ecological data-sets. The gradients are the basis for succinctly describing and visualizing the differential habitat preferences (niches) of taxa via an ordination diagram. Linear multivariate methods for relating two set of variables, such as PLS2, canonical correlation analysis and redundancy analysis, are less suited for this purpose because niches are often unimodal functions of habitat variables. After pointing out the key assumptions underlying CCA, the paper focusses on the interpretation of CCA ordination diagrams. Subsequently, some advanced uses, such as ranking environmental variables in importance and the statistical testing of effects are illustrated on a typical macroinvertebrate data-set. The paper closes with comparisons with correspondence analysis, discriminant analysis, PLS2 and co-inertia analysis

Entropy of the electroencephalogram as applied in the M-Entropy S/5TM Module (GE Healthcare) during increases in nitrous oxide and constant sevoflurane concentrations

BACKGROUND: It has been suggested that spectral entropy of the electroencephalogram as applied in the M-Entropy S/5TM Module (GE Healthcare) does not detect the effects of nitrous oxide (N2O). The aim of this study was to investigate the effect on entropy by graded increases in N2O concentrations in the presence of a constant concentration of sevoflurane, in the absence of surgical stimulation. METHOD: This single-blind, randomised study was conducted at an altitude of approximately 1 400 m. Patients received sevoflurane 2% (1.7% at sea level) and N2O, at end-tidal concentrations of 0%, 10%, 20%, 30%, 40%, 50%, 60% or 70% (equivalent to 8.5%, 17%, 25.5%, 34%, 42.6%, 51.1% and 59.6% at sea level). Entropy was measured before, during and after N2O administration. The absolute changes and ratios o f entropy relative to the baseline were calculated. Between- and within-group comparisons were made using analysis of variance and covariance. RESULTS: None of the entropy variables differed significantly within and between groups before and after N2O administration. Within-group analysis revealed that entropy during N2O administration was significantly lower than before or after N2O administration (P < 0.007). While a minor clinical but statistically significant linear relationship was observed between increasing N2O concentration and decreasing entropy from N2O 0% to 60%, a steeper and clinically important decrease (relative change > 20%) was noted at N2O > 60% (> 51% at sea level). CONCLUSIONS: The M-Entropy Module S/5TM responds to increasing concentrations of N2O in the presence of 2% (1.7% at sea level) sevoflurane, in the absence of surgical stimulation. There is a linear relationship between increasing N2O concentrations and decreasing entropy with a steep and clinically important decrease at N2O > 60% (> 51% at sea level). The influence of ambient pressure on the partial pressures, which determine the effects of anaesthetic agents, must be taken into account

The prevalence of intentional and unintentional injuries in selected Johannesburg housing settlements

Intentional and unintentional injuries were reported to be the second leading cause of Disability Adjusted Life Years in South Africa in 2000. We present household experiences of such injuries in 5 impoverished housing settlements in Johannesburg, Gauteng Province. Data for this study were extracted from the database of the Health, Environment and Development (HEAD) project. The incidence of reported intentional injuries was determined to be double that of unintentional injuries. Households in the Hospital Hill and Riverlea settlements reported the highest prevalence of stabbing and gunshot incidents. We concluded that impoverished South African neighbourhoods bear a high burden of intentional injury; surveillance mechanisms are required to inform prevention strategies at an individual, a community and a societal level.http://www.samj.org.zaam2017Clinical Epidemiolog

Airframe noise source localization using a microphone array

3rd AIAA/CEAS Aeroacoustics conference, Atlanta, GA (USA), May 12-14, 1997Available from INIST (FR), Document Supply Serviceunder shelf-number : 22419, issue : a.1997 n.47 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueSIGLEFRFranc