Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.568.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 24 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 1230months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.57,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Does land titling matter? The role of land property rights in the war on illicit crops in Colombia

This paper analyzes the role of formalization of land property rights in the war against illicit crops in Colombia. We argue that as a consequence of the increase of state presence and visibility during the period of 2000 and 2009, municipalities with a higher level of formalization of their land property rights saw a greater reduction in the area allocated to illicit crops. We hypothesize that this is due to the increased cost of growing illicit crops on formal land compared to informal, and due to the possibility of obtaining more benets in the newly in- stalled institutional environment when land is formalized. We exploit the variation in the level of formalization of land property rights in a set of municipalities that had their rst cadastral census collected in the period of 1994-2000; this selection procedure guarantees reliable data and an unbiased source of variation. Using fixed effects estimators, we found a signicant negative relationship between the level of formalization of land property rights and the number of hectares allocated to coca crops per municipality. These results remain robust through a number of sensitivity analyses. Our ndings contribute to the growing body of evidence on the positive effects of formal land property rights, and e ective policies in the war on drugs in Colombia.

Moral Hazard in Repeated Procurement of Services

This paper analyzes repeated procurement of services as a four-stage game divided into two periods. In each period there is (1) a contest stage à la Tullock in which the principal selects an agent and (2) a service stage in which the selected agent provides a service. Since this service effort is non-verifiable, the principal faces a moral hazard problem at the service stages. This work considers how the principal should design the period-two contest to mitigate the moral hazard problem in the period-one service stage and to maximize total service and contest efforts. It is shown that the principal must take account of the agent's past service effort in the period-two contest success function. The results indicate that the optimal way to introduce this `bias' is to choose a certain degree of complementarity between past service and current contest efforts. This result shows that contests with `additive bias' (`multiplicative bias') are optimal in incentive problems when effort cost is low (high). Furthermore, it is shown that the severity of the moral hazard problem increases with the cost of service effort (compared to the cost of contest effort) and the number of agents. Finally, the results are extended to more general contest success functions. JEL classification: C72; D82 Key words: Biased contests; Moral Hazard; Repeated Game; Incentives.

Available evidence and outcome of off-label use of rituximab in clinical practice

Purpose: To analyze the therapeutic indications for off-label use of rituximab, the available evidence for its use, the outcomes, and the cost. Methods: This was a retrospective analysis of patients treated with rituximab for off-label indications from January 2007 to December 2009 in two tertiary hospitals. Information on patient characteristics, medical conditions, and therapeutic responses was collected from medical records. Available evidence for the efficacy of rituximab in each condition was reviewed, and the cost of treatment was calculated. Results: A total of 101 cases of off-label rituximab use were analyzed. The median age of the patients involved was 53 [interquartile range (IQR) 37.5-68.0] years; 55.4 % were women. The indications for prescribing rituximab were primarily hematological diseases (46 %), systemic connective tissue disorders (27 %), and kidney diseases (20 %). Available evidence supporting rituximab treatment for these indications mainly came from individual cohort studies (53.5 % of cases) and case series (25.7 %). The short-term outcome (median 3 months, IQR 2-4 months) was a complete response in 38 % of cases and partial response in 32.6 %. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest was for neuromyelitis optica, idiopathic thrombocytopenic purpura, and miscellaneous indications. Some response was maintained in long-term follow-up (median 23 months IQR 12-30months) in 69.2%of patients showing a short-term response. Median cost per patient was 5,187.5 (IQR 5,187.5-7,781.3). Conclusions: In our study, off-label rituximab was mainly used for the treatment of hematological, kidney, and systemic connective tissue disorders, and the response among our patient cohort was variable depending on the specific disease. The level of evidence supporting the use of rituximab for these indications was low and the cost was very high. We conclude that more clinical trials on the off-label use of rituximab are needed, although these may be difficult to conduct in some rare diseases. Data from observational studies may provide useful information to assist prescribing in clinical practice.

Regional variability in the impact of human capital on regional growth

The first objective of this study is to furnish new evidence concerning the aggregate profitability of the accumulation of human capital. In addition to the traditional measure of the return to human capital, combining the information on its shadow price with the social cost of providing education allows us to confirm the profitability of human capital investments as a tool for promoting economic growth. The possibility of obtaining estimations of these effects for each Spanish region enables us to empirically evaluate the amount of heterogeneity across economies in the effects of human capital. As a second objective, we provide evidence on the indirect effect of human capital in making private capital investment more attractive. Among the main explanations for this process, we observe that higher worker skill levels enable higher returns to be extracted from investment in physical capital.

Effects of the epitaxial layer thickness on the noise properties of Schottky barrier diodes

An analytical theory to describe the combined effects of the epitaxial layer thickness and the ohmic contact on the noise properties of Schottky barrier diodes is presented. The theory, which provides information on both the local and the global noise properties, takes into account the finite size of the epitaxial layer and the effects of the back ohmic contact, and applies to the whole range of applied bias. It is shown that by scaling down the epitaxial layer thickness, the current regime in which the noise temperature displays a shot-noise-like behavior increases at the cost of reducing the current range in which the thermal-noise-like behavior dominates. This improvement in noise temperature is limited by the effects of the ohmic contact, which appear for large currents. The theory is formulated on general trends, allowing its application to the noise analysis of other semiconductor devices operating under strongly inhomogeneous distributions of the electric field and charge concentrations.

Effects of the epitaxial layer thickness on the noise properties of Schottky barrier diodes

An analytical theory to describe the combined effects of the epitaxial layer thickness and the ohmic contact on the noise properties of Schottky barrier diodes is presented. The theory, which provides information on both the local and the global noise properties, takes into account the finite size of the epitaxial layer and the effects of the back ohmic contact, and applies to the whole range of applied bias. It is shown that by scaling down the epitaxial layer thickness, the current regime in which the noise temperature displays a shot-noise-like behavior increases at the cost of reducing the current range in which the thermal-noise-like behavior dominates. This improvement in noise temperature is limited by the effects of the ohmic contact, which appear for large currents. The theory is formulated on general trends, allowing its application to the noise analysis of other semiconductor devices operating under strongly inhomogeneous distributions of the electric field and charge concentrations.

Citation auctions as a method to improve selection of scientific papers

This paper describes the basis of citation auctions as a new approach to selecting scientific papers for publication. Our main idea is to use an auction for selecting papers for publication through - differently from the state of the art - bids that consist of the number of citations that a scientist expects to receive if the paper is published. Hence, a citation auction is the selection process itself, and no reviewers are involved. The benefits of the proposed approach are two-fold. First, the cost of refereeing will be either totally eliminated or significantly reduced, because the process of citation auction does not need prior understanding of the paper's content to judge the quality of its contribution. Additionally, the method will not prejudge the content of the paper, so it will increase the openness of publications to new ideas. Second, scientists will be much more committed to the quality of their papers, paying close attention to distributing and explaining their papers in detail to maximize the number of citations that the paper receives. Sample analyses of the number of citations collected in papers published in years 1999-2004 for one journal, and in years 2003-2005 for a series of conferences (in a totally different discipline), via Google scholar, are provided. Finally, a simple simulation of an auction is given to outline the behaviour of the citation auction approach