A cost-effectiveness analysis of two anti-EGFR monoclonal antibodies (cetuximab and panitumumab) plus best supportive care versus best supportive care alone as third-line treatment of advanced chemorefractory metastatic colorectal cancer

ABSTRACT Introduction The National Cancer Institute of Canada Clinical Trials Group CO. 17 trial and the Open-Label Phase III trial showed that the addition of new anti-EGFR monoclonal antibodies (cetuximab andpanitumumab) to best supportive care as third-line treatments prolong the life of patients with advanced metastatic colorectal cancer, but have also introduced a unique set of toxicities and increased costs. In a resource constrained environment this prompts the need for tools to identify the patients who are likely to benefit from these therapies in a more efficient and cost-effective way. We developed an economic model using analytic decision modeling to assess the cost-effectiveness of two anti-EGFR monoclonal antibodies (cetuximab and panitumumab) plus best supportive care versus best supportive care alone as third-line treatment in advanced chemorefractory metastatic colorectal cancer. Methods We constructed a Markov model based on the efficacy data obtained from the National Cancer Institute of Canada Clinical Trials Group CO. 17 trial and the Open-Label Phase III trial studies. Costs for physician visits, blood products, emergency department visits, hospitalizations and toxicity management were obtained published literature and expert opinion. Drug costs were obtained from London Health Sciences Center (LHSC) drug formulary intranet. The primary outcome of the model is the incremental cost-utility ratio of adding anti-EGFR monoclonal antibodies (panitumumab and cetuximab) to best supportive care as third-line therapies in treatment of advanced metastatic chemo-refractory colorectal cancer, expressed as cost per quality-adjusted life year (QALY) gained. A series of deterministic and probabilistic sensitivity analyses were also performed to account for uncertainty in the model parameters. Results Adding panitumumab to best supportive care (with KRAS test) resulted in a mean gain of 0.087 QALYs with a mean incremental cost utility ratio of $269,703 per QALY gained (95$135,432 to $766,072 per QALY gained). The addition of cetuximab to best supportive care (with KRAS test) resulted in a mean gain of 0.068 QALYs with a mean incremental cost-utility ratio of$352,046 per QALY gained (95% Cl = $151,916 to$949,342 per QALY gained). In subset of patients with wild-type KRAS, the addition of panitumumab to best supportive care resulted in a mean gain of 0.16 QALYs with a mean incremental cost-utility ratio of $236,469 per QALY gained (95$125,259 to $557,750 per QALY gained). Conclusions From a health economic perspective, both anti-EFGR therapies (panitumumab and cetuximab) showed very high Incremental cost-utility ratios and were not cost-effective at a willingness-to-pay threshold of$100,000 per QALY. The cost-utility ratios were much more favorable in subset of patients with wild-type KRAS. This suggests that personalizing advanced metastatic colorectal cancer treatment based on KRAS mutation status could not only save health care system substantial sums but also spare thousands of patients with metastatic colorectal cancer from side effects of the anti-EGFR therapies that are unlikely to benefit from the treatment

Surgery transformations and spectral estimates of δ\delta beam operators

We introduce $\delta$ type vertex conditions for beam operators, the fourth derivative operator, on metric graphs and study the effect of certain geometrical alterations (graph surgery) of the graph on the spectra of beam operators on compact metric graphs. Results are obtained for a class of vertex conditions which can be seen as an analogue of {\delta} vertex conditions for quantum graphs. There are a number of possible candidates of {\delta} type conditions for beam operators. We develop surgery principles and record the monotonicity properties of the spectrum, keeping in view the possibility that vertex conditions may change within the same class after certain graph alterations. We also demonstrate the applications of surgery principles by obtaining several lower and upper estimates on the eigenvalues

Management of Depressed Skull Fracture: A Study of 93 Cases

Objective:  To determine the correlation of skull fracture with dural tear in head injury patients presenting to a tertiary care hospital. Patients and Methods:  This study was carried out at Lady Reading Hospital Peshawar from January 2008 to December 2008. All patients who were operated for depressed skull fracture during this study period ware included in the study. X-ray skull and CT scan brain were done for all patients; side and site of skull fracture were noted on imaging and during surgery. The incidence of dural tear associated with depressed skull fracture in various age groups and gender was noted. The results were analyzed using SPSS various 11. Results:  A total of 93 patients of depressed skull fracture were operated. There were 64 male and 29 female. Fall from the height was the main cause of trauma (61.3%). Most of the patients presented with moderate head injury. Dural injury was noted in 59.1% of the cases leading to neurodeficit in the form of hemeparesis/ hemiplegia in majority of cases. All patients were operated elevating the depressed fragments and dura repaired. Conclusion:  Dural injury is associated with morbidity in the form of hemiparesis / hemiplegia in patient having depressed skull fracture mainly at franto-patietal region for which prompt surgical intervention and dural repair are the procedures of choice. Key Words:  Depressed skull fracture, head trauma, duroplasty

Analysis of Financial Sector Reforms and Impacts: Reflections from Pakistan

The purpose of this paper is to examine all efforts made by the Government of Pakistan in order to uplift the efficiency of financial sector through financial restructuring institutions such as banks, as well as to recognize the impact of these reforms on various financial indicators. Results of this study suggested that financial sector performance was very much better after the completion of first generation reforms but many new reforms are still required for macroeconomic stability and economic growth of Pakistan. This was the first attempt made by researcher in which detailed discussion was provided about financial sector reforms and it will help out the policy makers while developing policies for future and it will enhance the knowledge of economists and all other beneficiaries as well. Moreover, discussion for further reforms and gap for future studies was also provided

Classification of Electrospinning Methods

Electrospun nanofibers are being used in a variety of performance apparel applications where their unique properties add to their functionality. Those properties include, small fiber diameter, high surface area, potential to combine chemistry, layer thinness, high porosity, filtration properties, and low basis weight. Electrospinning has been considered as an efficient technique for nanofiber web formation. Polymers have been electrospun into nanofibers mostly after being dissolved in solvent and melted. This chapter presents a comprehensive summary of existing electrospinning methods. Electrospinning methods are classified into different categories depend upon jet formation

Firm Specific Determinants of Growth in a Post CPEC Situation

Purpose: The study explores  the determinant of firm growth in a post CPEC scenario by taking a panel data of 53 textile based firms listed on Pakistan Stock Exchange (PSX). Approach/Methodology/Design: The data were extracted from the Financial Statement Analysis (FSA) published by State Bank of Pakistan for a period ranging from 2012 to 2017. In this research, we applied some methods to evaluate results descriptive statistics, correlation analysis and regression models such as random effect model, fixed effect model and pooled OLS and also we use GMM method (generalized method of movement).  Findings: The results after the calibration of CPEC as dummy variable proved that profitability and financial leverage are significant determinants of firm growth in the textile sector of Pakistan even after controlling the endogeneity problems.   Originality/value: The results imply that the firms in textile sector should focus on sustained profitability and also the availability of healthy financial arrangements to pursue growth in the long term

Harnessing the Potential of Blockchain in DevOps: A Framework for Distributed Integration and Development

As the use of DevOps practices continues to grow, organizations are seeking ways to improve collaboration, speed up development cycles, and increase security, transparency, and traceability. Blockchain technology has the potential to support these goals by providing a secure, decentralized platform for distributed integration and development. In this paper, we propose a framework for distributed DevOps that utilizes the benefits of blockchain technology that can eliminate the shortcomings of DevOps. We demonstrate the feasibility and potential benefits of the proposed framework that involves developing and deploying applications in a distributed environment. We present a benchmark result demonstrating the effectiveness of our framework in a real-world scenario, highlighting its ability to improve collaboration, reduce costs, and enhance the security of the DevOps pipeline. Conclusively, our research contributes to the growing body of literature on the intersection of blockchain and DevOps, providing a practical framework for organizations looking to leverage blockchain technology to improve their development processes.Comment: pages 10, figures

A study of the GAM approach to solve laminar boundary layer equations in the presence of a wedge

We apply an easy and simple technique, the generalized ap- proximation method (GAM) to investigate the temperature field associated with the Falkner-Skan boundary-layer problem. The nonlinear partial differ- ential equations are transformed to nonlinear ordinary differential equations using the similarity transformations. An iterative scheme for the non-linear ordinary differential equations associated with the velocity and temperature profiles are developed via GAM. Numerical results for the dimensionless ve- locity and temperature profiles of the wedge flow are presented graphically for different values of the wedge angle and Prandtl number