Fosfomycin versus meropenem in bacteraemic urinary tract infections caused by extended-spectrum β-lactamase-producing Escherichia coli (FOREST): study protocol for an investigator-driven randomised controlled trial.

INTRODUCTION Finding therapeutic alternatives to carbapenems in infections caused by extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) is imperative. Although fosfomycin was discovered more than 40 years ago, it was not investigated in accordance with current standards and so is not used in clinical practice except in desperate situations. It is one of the so-called neglected antibiotics of high potential interest for the future. METHODS AND ANALYSIS The main objective of this project is to demonstrate the clinical non-inferiority of intravenous fosfomycin with regard to meropenem for treating bacteraemic urinary tract infections (UTI) caused by ESBL-EC. This is a 'real practice' multicentre, open-label, phase III randomised controlled trial, designed to compare the clinical and microbiological efficacy, and safety of intravenous fosfomycin (4 g/6 h) and meropenem (1 g/8 h) as targeted therapy for this infection; a change to oral therapy is permitted after 5 days in both arms, in accordance with predetermined options. The study design follows the latest recommendations for designing trials investigating new options for multidrug-resistant bacteria. Secondary objectives include the study of fosfomycin concentrations in plasma and the impact of both drugs on intestinal colonisation by multidrug-resistant Gram-negative bacilli. ETHICS AND DISSEMINATION Ethical approval was obtained from the Andalusian Coordinating Institutional Review Board (IRB) for Biomedical Research (Referral Ethics Committee), which obtained approval from the local ethics committees at all participating sites in Spain (22 sites). Data will be presented at international conferences and published in peer-reviewed journals. DISCUSSION This project is proposed as an initial step in the investigation of an orphan antimicrobial of low cost with high potential as a therapeutic alternative in common infections such as UTI in selected patients. These results may have a major impact on the use of antibiotics and the development of new projects with this drug, whether as monotherapy or combination therapy. TRIAL REGISTRATION NUMBER NCT02142751. EudraCT no: 2013-002922-21. Protocol V.1.1 dated 14 March 2014.

Competition and cost overruns. Optimal misspecification of procurement contracts

Most cases of cost overruns in public procurement are related to important changes in the initial project design. This paper deals with the problem of design specification in public procurement and provides a rationale for design misspecification. We propose a model in which the sponsor decides how much to invest in design specification and awards competitively the project to a contractor. After the project has been awarded the sponsor engages in bilateral renegotiation with the contractor, in order to accommodate changes in the initial project s design that new information makes desirable. When procurement takes place in the presence of horizontally differentiated contractors, the design s specification level is seen to affect the resulting degree of competition. The paper highlights this interaction between market competition and design specification and shows that the sponsor s optimal strategy, when facing an imperfectly competitive market supply, is to underinvest in design specification so as to make significant cost overruns likely. Since no such misspecification occurs in a perfectly competitive market, cost overruns are seen to arise as a consequence of lack of competition in the procurement market.

Allocating ideas: Horizontal competition in tournaments

We develop a stylized model of horizontal and vertical competition intournaments with two competing firms. The sponsor cares about the qualityof the design but also about the design location. A priori not even thesponsor knows his preferred design location, which is only discoveredonce he has seen the actual proposals. We show that the more efficientfirm is more likely to be conservative when choosing the design location.Also, to get some differentiation in design locations, the cost differencebetween contestants can neither be too small nor too big. Therefore, ifthe sponsor mainly cares about the design location, participation in thetournaments by the two lowest cost contestants cannot be optimal for thesponsor.

Competition and cost overruns in procurement

Most cases of cost overruns in public procurement are related to important changes in theinitial project design. This paper deals with the problem of design speciffication in public procurement and provides a rationale for design misspeciffication. We propose a model in which the sponsor decides how much to invest in design speciffication and awards competitively the project to a contractor. After the project has been awarded the sponsor engages in bilateral renegotiation with the contractor, in order to accommodate changes in the initial project's design that new information makes desirable. When procurement takes place in the presence of horizontally differentiated contractors, the design's speciffication level is seen to affect the resulting degree of competition. The paper highlights this interaction between market competition and design speciffication and shows that the sponsor's optimal strategy, when facing an imperfectly competitive market supply, is to underinvest in design speciffication so as to make signifficant cost overrunslikely. Since no such misspeciffication occurs in a perfectly competitive market, cost overruns are seen to arise as a consequence of lack of competition in the procurement market.

Heterogeneity-promoting optimal procurement

When procurement takes place in the presence of horizontally differentiated contractors, the design of the object being procured affects the resulting degree of competition. This paper highlights the interaction between theoptimal procurement mechanism and the design choice. Contrary to conventional wisdom, the sponsor's design choice, instead of homogenizingthe market to generate competition, promotes heterogeneity.

How a Bill Becomes a Law, September 18, 2008

A legislative bill is a written proposal for a law. Ideas for bills come from many sources: a legislator’s constituents, businesses, government agencies, professional associations, interest groups and other state legislatures. When a legislator recognizes or is made aware of a problem which could be pursued through legislation, that idea is put into the form of a bill. In Iowa, only legislators are able to sponsor and introduce bills. Bills may be sponsored by a Senator or Representative, or by a Senate or House committee. All bills must be approved by both the Senate and the House before being sent to the Governor for final approval. When a bill is introduced by members of a legislative chamber, it must follow a process and, if passed, be sent to members in the other legislative chamber where this process is repeated. The bill and its language must be in identical form from both chambers before being sent to the Governor.

Sponsoring a refugee family, 2002

This brochure gives information on how to sponsor a refugee family. Sponsors provide support and friendship necessary to ease the transition between cultures.

Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.

BACKGROUND: Interleukin 6 is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Our aim was to assess the therapeutic effects of blocking interleukin 6 by inhibition of the interleukin-6 receptor with tocilizumab in patients with rheumatoid arthritis. METHODS: In this double-blind, randomised, placebo-controlled, parallel group phase III study, 623 patients with moderate to severe active rheumatoid arthritis were randomly assigned with an interactive voice response system, stratified by site with a randomisation list provided by the study sponsor, to receive tocilizumab 8 mg/kg (n=205), tocilizumab 4 mg/kg (214), or placebo (204) intravenously every 4 weeks, with methotrexate at stable pre-study doses (10-25 mg/week). Rescue therapy with tocilizumab 8 mg/kg was offered at week 16 to patients with less than 20% improvement in both swollen and tender joint counts. The primary endpoint was the proportion of patients with 20% improvement in signs and symptoms of rheumatoid arthritis according to American College of Rheumatology criteria (ACR20 response) at week 24. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00106548. FINDINGS: The intention-to-treat analysis population consisted of 622 patients: one patient in the 4 mg/kg group did not receive study treatment and was thus excluded. At 24 weeks, ACR20 responses were seen in more patients receiving tocilizumab than in those receiving placebo (120 [59%] patients in the 8 mg/kg group, 102 [48%] in the 4 mg/kg group, 54 [26%] in the placebo group; odds ratio 4.0 [95% CI 2.6-6.1], p<0.0001 for 8 mg/kg vs placebo; and 2.6 [1.7-3.9], p<0.0001 for 4 mg/kg vs placebo). More people receiving tocilizumab than those receiving placebo had at least one adverse event (143 [69%] in the 8 mg/kg group; 151 [71%] in the 4 mg/kg group; 129 [63%] in the placebo group). The most common serious adverse events were serious infections or infestations, reported by six patients in the 8 mg/kg group, three in the 4 mg/kg group, and two in the placebo group. INTERPRETATION: Tocilizumab could be an effective therapeutic approach in patients with moderate to severe active rheumatoid arthritis. FUNDING: F Hoffmann-La Roche, Chugai Pharmaceutical.

Building legitimacy by criticising the pharmaceutical industry: a qualitative study among prescribers and local opinion leaders.

PRINCIPLES: The literature has described opinion leaders not only as marketing tools of the pharmaceutical industry, but also as educators promoting good clinical practice. This qualitative study addresses the distinction between the opinion-leader-as-marketing-tool and the opinion-leader-as-educator, as it is revealed in the discourses of physicians and experts, focusing on the prescription of antidepressants. We explore the relational dynamic between physicians, opinion leaders and the pharmaceutical industry in an area of French-speaking Switzerland. METHODS: Qualitative content analysis of 24 semistructured interviews with physicians and local experts in psychopharmacology, complemented by direct observation of educational events led by the experts, which were all sponsored by various pharmaceutical companies. RESULTS: Both physicians and experts were critical of the pharmaceutical industry and its use of opinion leaders. Local experts, in contrast, were perceived by the physicians as critical of the industry and, therefore, as a legitimate source of information. Local experts did not consider themselves opinion leaders and argued that they remained intellectually independent from the industry. Field observations confirmed that local experts criticised the industry at continuing medical education events. CONCLUSIONS: Local experts were vocal critics of the industry, which nevertheless sponsor their continuing education. This critical attitude enhanced their credibility in the eyes of the prescribing physicians. We discuss how the experts, despite their critical attitude, might still be beneficial to the industry's interests.

Innovation – from individual intuition to collaborative innovation. The role of individual key actor in facilitation of innovation in large organization context

The objective of this research was to study the role of key individuals in facilitation of technology enabled bottom-up innovation in large organization context. The development of innovation was followed from the point of view of individual actor (key individual) in two cases, through three levels: individual, team and organization, by using knowledge creation and innovation models. This study provides theoretical synthesis and framework through which the study is driven. The results of the study indicate, that in bottom-up initiated innovations the role of key individuals is still crucial, but innovation today is collective effort and there acts several entrepreneurial key individuals: innovator, user champion and organizational sponsor, whose collaboration and developing interaction drives innovation further. The team work is functional and fluent, but it meets great problems in interaction with organization. The large organizations should develop its practices and ability to react on emerging bottom-up initiations, in order to embed innovation to organization and gain sustainable innovation. In addition, bottom-up initiated innovations are demonstrations of peoples knowing, tacit knowledge and therefore renewing of an organization.

Ensuring the efficient utilization of Business Intelligence

In recent years, chief information officers (CIOs) around the world have identified Business Intelligence (BI) as their top priority and as the best way to enhance their enterprises competitiveness. Yet, many enterprises are struggling to realize the business value that BI promises. This discrepancy causes important questions, for example: what are the critical success factors of Business Intelligence and, more importantly, how it can be ensured that a Business Intelligence program enhances enterprises competitiveness. The main objective of the study is to find out how it can be ensured that a BI program meets its goals in providing competitive advantage to an enterprise. The objective is approached with a literature review and a qualitative case study. For the literature review the main objective populates three research questions (RQs); RQ1: What is Business Intelligence and why is it important for modern enterprises? RQ2: What are the critical success factors of Business Intelligence programs? RQ3: How it can be ensured that CSFs are met? The qualitative case study covers the BI program of a Finnish global manufacturer company. The research questions for the case study are as follows; RQ4: What is the current state of the case company’s BI program and what are the key areas for improvement? RQ5: In what ways the case company’s Business Intelligence program could be improved? The case company’s BI program is researched using the following methods; action research, semi-structured interviews, maturity assessment and benchmarking. The literature review shows that Business Intelligence is a technology-based information process that contains a series of systematic activities, which are driven by the specific information needs of decision-makers. The objective of BI is to provide accurate, timely, fact-based information, which enables taking actions that lead to achieving competitive advantage. There are many reasons for the importance of Business Intelligence, two of the most important being; 1) It helps to bridge the gap between an enterprise’s current and its desired performance, and 2) It helps enterprises to be in alignment with key performance indicators meaning it helps an enterprise to align towards its key objectives. The literature review also shows that there are known critical success factors (CSFs) for Business Intelligence programs which have to be met if the above mentioned value is wanted to be achieved, for example; committed management support and sponsorship, business-driven development approach and sustainable data quality. The literature review shows that the most common challenges are related to these CSFs and, more importantly, that overcoming these challenges requires a more comprehensive form of BI, called Enterprise Performance Management (EPM). EPM links measurement to strategy by focusing on what is measured and why. The case study shows that many of the challenges faced in the case company’s BI program are related to the above-mentioned CSFs. The main challenges are; lack of support and sponsorship from business, lack of visibility to overall business performance, lack of rigid BI development process, lack of clear purpose for the BI program and poor data quality. To overcome these challenges the case company should define and design an enterprise metrics framework, make sure that BI development requirements are gathered and prioritized by business, focus on data quality and ownership, and finally define clear goals for the BI program and then support and sponsor these goals.

Value creation through sponsorship in electronic sports

The objective of this thesis was to study value creation through sponsor-ship in a new emerging electronic sports environment. Sub-questions were formulated which helped in finding answers to the main research question. Theory of traditional sports and practice of electronic sports were compared with each other in order to find out how theories of tradi-tional sports fare in the new environment. B2B-relationship model of Actors, resources and activities is used in this thesis to help in clarifying the different variables used in electronic sports sponsorship environment. The empirical research was conducted via interviews with the managers working in electronic sports environment. One of the main conclusions is that relationship management is really important.. Actors in electronic sports need to find and create win-win-win situations. This means that they need to benefit the actors in sponsoring relationship and also the community.

The corporate bias and the molding of prescription practices: the case of hypertension

Drug management of hypertension has been a noticeable example of the influence of the pharmaceutical industry on prescription practices. The worldwide leading brands of blood pressure-lowering agents are angiotensin receptor-blocking agents, although they are considered to be simply substitutes of angiotensin-converting enzyme (ACE) inhibitors. Commercial strategies have been based on the results of clinical trials sponsored by drug companies. Most of them presented distortions in their planning, presentation or interpretation that favored the drugs from the sponsor, i.e., corporate bias. Atenolol, an ineffective blood pressure agent in elderly individuals, was the comparator drug in several trials. In a re-analysis of the INSIGHT trial, deaths appeared to have been counted twice. The LIFE trial appears in the title of more than 120 reproductions of the main and flawed trial, as a massive strategy of scientific marketing. Most guidelines have incorporated the corporate bias from the original studies, and the evidence from better designed studies, such as the ALLHAT trial, have been largely ignored. In trials published recently corporate influences have touched on ethical limits. In the ADVANCE trial, elderly patients with type 2 diabetes and cardiovascular disease or risk factors, allocated to placebo, were not allowed to use diuretic and full doses of an ACE inhibitor, despite the sound evidence of benefit demonstrated in previous trials. As a consequence, they had a 14% higher mortality rate than the participants allocated to the active treatment arm. This reality should be modified immediately, and a greater independence of the academy from the pharmaceutical industry is necessary.

Why to invest more in women's football for your brand and your business?

The aim of this master’s thesis is to study the role of sponsorship in the business value of companies and clubs. In order to achieve this goal, the French women’s football context is studied. The main research question is formulated as follows: What is the business value in sport sponsorship? The literature and theory part consists of three chapters that clearly follow the theoretical framework: from the sport sponsorship to the sponsor brand, from the sponsor brand to the brand equity, from the brand equity to the business value. The empirical part of the master’s thesis is based on qualitative research method. Face-to-face interviews were conducted with 4 participants who are Sponsorship Manager or General Manager of French women’s football clubs or sponsors and thus considered as specialists of the study context. The results of the study show that the planning process, the objectives, the sponsor brand, the brand equity components such as the customer behaviour, the economic, financial and immaterial values have positive impacts on the business value in sport sponsorship in the French women’s football context.

Urheilusponsorointi yrityksen markkinointiviestintätyökaluna

Tutkielma keskittyy kuvailemaan urheilun sponsorointia yrityksen markkinointiviestinnän välineenä. Aiheeseen lähestytään tutkielmassa yrityksen näkökulmasta, jossa käsitellään keskeisiä sponsorointiin liittyviä ilmiöitä ja ulottuvuuksia. Tutkielma sisältää empiirisen osuuden haastattelun moudossa.