Characteristics of ambulatory anticoagulant adverse drug events: a descriptive study

<p>Abstract</p> <p>Background</p> <p>Despite the high frequency with which adverse drug events (ADEs) occur in outpatient settings, detailed information regarding these events remains limited. Anticoagulant drugs are associated with increased safety concerns and are commonly involved in outpatient ADEs. We therefore sought to evaluate ambulatory anticoagulation ADEs and the patient population in which they occurred within the Duke University Health System (Durham, NC, USA).</p> <p>Methods</p> <p>A retrospective chart review of ambulatory warfarin-related ADEs was conducted. An automated trigger surveillance system identified eligible events in ambulatory patients admitted with an International Normalized Ratio (INR) >3 and administration of vitamin K. Event and patient characteristics were evaluated, and quality/process improvement strategies for ambulatory anticoagulation management are described.</p> <p>Results</p> <p>A total of 169 events in 167 patients were identified from December 1, 2006-June 30, 2008 and included in the study. A median supratherapeutic INR of 6.1 was noted, and roughly half of all events (52.1%) were associated with a bleed. Nearly 74% of events resulted in a need for fresh frozen plasma; 64.8% of bleeds were classified as major. A total of 59.2% of events were at least partially responsible for hospital admission. Median patient age was 68 y (range 36-95 y) with 24.9% initiating therapy within 3 months prior to the event. Of events with a prior documented patient visit (n = 157), 73.2% were seen at a Duke clinic or hospital within the previous month. Almost 80% of these patients had anticoagulation therapy addressed, but only 60.0% had a follow-up plan documented in the electronic note.</p> <p>Conclusions</p> <p>Ambulatory warfarin-related ADEs have significant patient and healthcare utilization consequences in the form of bleeding events and associated hospital admissions. Recommendations for improvement in anticoagulation management include use of information technology to assist monitoring and follow-up documentation, avoid drug interactions, and engage patients in their care.</p

IMPaCT Back study protocol. Implementation of subgrouping for targeted treatment systems for low back pain patients in primary care: a prospective population-based sequential comparison.

BACKGROUND: Prognostic assessment tools to identify subgroups of patients at risk of persistent low back pain who may benefit from targeted treatments have been developed and validated in primary care. The IMPaCT Back study is investigating the effects of introducing and supporting a subgrouping for targeted treatment system in primary care. METHODS/DESIGN: A prospective, population-based, quality improvement study in one Primary Care Trust in England with a before and after design. Phases 1 and 3 collect data on current practice, attitudes and behaviour of health care practitioners, patients' outcomes and health care costs. Phase 2 introduces and supports the subgrouping for targeted treatment system, via a multi-component, quality improvement intervention that includes educational courses and outreach visits led by opinion leaders, audit/feedback, mentoring and organisational support to embed the subgrouping tools within IT and clinical management systems.We aim to recruit 1000 low back pain patients aged 18 years and over consulting 7 GP practices within one Primary Care Trust in England, UK. The study includes GPs in participating practices and physiotherapists in associated services. The primary objective is to determine the effect of the subgrouping for targeted treatment system on back pain related disability and catastrophising at 2 and 6 months, comparing data from phase 1 with phase 3. Key secondary objectives are to determine the impact on: a) GPs' and physiotherapists' attitudes and behaviour regarding low back pain; b) The process of care that patients receive; c) The cost-effectiveness and sustainability of the new clinical system. DISCUSSION: This paper details the rationale, design, methods, planned analysis and operational aspects of the IMPaCT Back study. We aim to determine whether the new subgrouping for targeted treatment system is implemented and sustained in primary care, and evaluate its impact on clinical decision-making, patient outcomes and costs. STUDY REGISTRATION: International Standard Randomised Controlled Trial Number Register ISRCTN55174281.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element

Gene regulation relies on dynamic changes in three-dimensional chromatin conformation, which are shaped by composite regulatory and architectural elements. However, mechanisms that govern such conformational switches within chromosomal domains remain unknown. We identify a novel mechanism by which cis-elements promote long-range interactions, inducing conformational changes critical for diversification of the TCRβ antigen receptor locus (Tcrb). Association between distal Vβ gene segments and the highly expressed DβJβ clusters, termed the recombination center (RC), is independent of enhancer function and recruitment of V(D)J recombinase. Instead, we find that tissue-specific folding of Tcrb relies on two distinct architectural elements located upstream of the RC. The first, a CTCF-containing element, directly tethers distal portions of the Vβ array to the RC. The second element is a chromatin barrier that protects the tether from hyperactive RC chromatin. When the second element is removed, active RC chromatin spreads upstream, forcing the tether to serve as a new barrier. Acquisition of barrier function by the CTCF element disrupts contacts between distal Vβ gene segments and significantly alters Tcrb repertoires. Our findings reveal a separation of function for RC-flanking regions, in which anchors for long-range recombination must be cordoned off from hyperactive RC landscapes by chromatin barriers

NuMA Overexpression in Epithelial Ovarian Cancer

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon