Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Pockets of flexibility in workflow specification

Workflow technology is currently being deployed in quite diverse domains. However, the element of change is present in some degree and form in almost all domains. A workflow implementation that does not support the process of change will not benefit the organization in the long run. Change can be manifested in different forms in workflow processes. In this paper, we first present a categorization of workflow change characteristics and divide workflow processes into dynamic, adaptive and flexible processes. We define flexibility as the ability of the workflow process to execute on the basis of a loosely, or partially specified model, where the full specification of the model is made at runtime, and may be unique to each instance. To provide a modeling framework that offers true flexibility, we need to consider the factors, which influence the paths of (unique) instances together with the process definition. We advocate an approach that aims at making the process of change part of the workflow process itself. We introduce the notion of an open instance that consists of a core process and several pockets of flexibility, and present a framework based on this notion, which makes use of special build activities that provide the functionality to integrate the process of defining a change, into the open workflow instance

The Role of Messaging in Collaborative Business Processes *

Business process management technologies are considered as one of the key success stories in providing process control and addressing complex integration requirements. However, the expectation of what this technology must deliver is a moving target. What was true for workflow systems is no longer acceptable in the dynamic and cross organizational requirements for management of collaborative processes. Whereas the success of coordinative processes depends upon the conformance to the prescribed control flow, the success of the collaborative process depends upon the ability to detect and react to changing conditions. In this paper we highlight the differences between the well known coordinative and emerging collaborative processes and present key distinguishing characteristics. We further deliberate on the widely established role of messaging as an enabling technology for inter and intra process communication. Acknowledging the role of messaging, and the distinct requirements posed by collaborative processes, we question the appropriateness of current control flow driven approaches and propose an alternative mode of thought for addressing the modeling and execution of collaborative business processes. This paper is not intended to present a complete solution of the alternative approach, but to identify it as a viable research direction and a potentially more appropriate approach

When workflows will not deliver – The case of contradicting work practice

A new class of problems has been identified for workflow management wherein this technology imposes an additional overhead on users which is not adequately compensated by the benefits gained. Multiple observations from real cases identify a contradiction between the preferred work practice and some fundamental principles behind workflow systems. The focus of this paper is primarily to motivate the problem, however, we will also provide deliberations on the impact of these advanced process requirements on existing technology solutions. 1

COLLABORATIVE BUSINESS PROCESS MANAGEMENT THROUGH HARMONIZED MESSAGING

Technologies in general, have significantly contributed to overcoming some of the integration problems of intra and inter enterprise process control and monitoring. However, the complexity of the interactions between heterogeneous and autonomous systems within the enterprise and often between trading partners in ever increasing. A number of initiatives and proposals are underway to provide solutions for process specification and communication. However, the focus is often on defining APIs and interfaces rather than the semantics of the underlying interactions. On the other hand messaging technologies are well positioned as the key enabling technology for facilitating these interactions. Although messaging systems have traditionally had a different agenda dominated by scalability and performance, we see a great potential in the enhancement of current messaging infrastructure, in its new role in facilitating complex, long running interactions for dynamic and collaborative processes operating in decentralized environments like the web. In this paper, we primarily present a vision for a technology aimed at providing a level of harmonization to multiple messages to form a single custom definable backbone. We will provide the foundation framework for the harmonized messaging technology and identify fundamental issues for the management of such complex interactions.

Data Flow and Validation in Workflow Modelling

A complete workflow specification requires careful integration of many different process characteristics. Decisions must be made as to the definitions of individual activities, their scope, the order of execution that maintains the overall business process logic, the rules governing the discipline of work list scheduling to performers, identification of time constraints and more. The goal of this paper is to address an important issue in workflows modelling and specification, which is data flow, its modelling, specification and validation. Researchers have neglected this dimension of process analysis for some time, mainly focussing on structural considerations with limited verification checks. In this paper, we identify and justify the importance of data modelling in overall workflows specification and verification. We illustrate and define several potential data flow problems that, if not detected prior to workflow deployment may prevent the process from correct execution, execute process on inconsistent data or even lead to process suspension. A discussion on essential requirements of the workflow data model in order to support data validation is also given

On sensor network segmentation for urban water distribution monitoring

Identifying water wastage in forms of leaks in a water distribution network of any city becomes essential as droughts are presenting serious threats to few major cities. In this paper, we propose a deployment of sensor network for monitoring water flow in any water distribution network. We cover the issues related with designing such a dedicated sensor network by considering types of sensors required, sensors' functionality, data collection, and providing computation serving as leak detection mechanism. The main focus of this paper is on appropriate network segmentation that provides the base for hierarchical approach to pipes' failure detection. We show a method for sensors allocation to the network in order to facilitate effective pipes monitoring. In general, the identified computational problem belongs to hard problems. The paper shows a heuristic method to build effective hierarchy of the network segmentation