Bleeding risks associated with vitamin K antagonists

Vitamin K antagonists are widely used for the prevention of stroke due to atrial fibrillation, treatment and secondary prevention of venous thromboembolism, prevention of valvular thromboembolism in patients with prosthetic heart valves, and secondary prevention of acute myocardial infarction. The most common adverse event experienced by patients receiving anticoagulant therapy is major bleeding. The incidence of major bleeding in patients receiving long-term anticoagulation with a vitamin K antagonist in contemporary studies is 1–3% per year. To determine if the benefits of anticoagulant therapy outweigh the risk of bleeding in an individual patient, physicians must be aware of the risk factors associated with major bleeding. This narrative review will provide an overview of the incidence of major bleeding in patients receiving therapeutic anticoagulant therapy with vitamin K antagonists, discuss the risk factors for bleeding, and outline the most commonly used clinical prediction rules for bleeding.     

Development and validation of a diagnostic prediction model distinguishing complicated from uncomplicated diverticulitis

Abstract

Objectives: Most diverticulitis patients (80%) who are referred to secondary care have uncomplicated diverticulitis (UD) which is a self-limiting disease and can be treated at home. The aim of this study is to develop a diagnostic model that can safely rule out complicated diverticulitis (CD) based on clinical and laboratory parameters to reduce unnecessary referrals.

Methods: A retrospective cross-sectional study was performed including all patients who presented at the emergency department with CT-proven diverticulitis. Patient characteristics, clinical signs and laboratory parameters were collected. CD was defined as?>?Hinchey 1A. Multivariable logistic regression analyses were used to quantify which (combination of) variables were independently related to the presence or absence of CD. A diagnostic prediction model was developed and validated to rule out CD.

Results: A total of 943 patients were included of whom 172 (18%) had CD. The dataset was randomly split into a derivation and validation set. The derivation dataset contained 475 patients of whom 82 (18%) patients had CD. Age, vomiting, generalized abdominal pain, change in bowel habit, abdominal guarding, C-reactive protein and leucocytosis were univariably related to CD. The final validated diagnostic model included abdominal guarding, C-reactive protein and leucocytosis (AUC 0.79 (95% CI 0.73–0.84)). At a CD risk threshold of ≤7.5% this model had a negative predictive value of 96%.

Conclusion: This proposed prediction model can safely rule out complicated diverticulitis. Clinical practitioners could cautiously use this model to aid them in the decision whether or not to subject patients to further secondary care diagnostics or treatment.     

An i2b2-based,generalizable, open source,self-scaling chronic disease registry

Objective

Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software.

Materials and methods

Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions.

Results

The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA.

Discussion

We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing.

Conclusions

The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.     

Review: Pathology imaging informatics for quantitative analysis of whole-slide images

Objectives

With the objective of bringing clinical decision support systems to reality, this article reviews histopathological whole-slide imaging informatics methods, associated challenges, and future research opportunities.

Target audience

This review targets pathologists and informaticians who have a limited understanding of the key aspects of whole-slide image (WSI) analysis and/or a limited knowledge of state-of-the-art technologies and analysis methods.

Scope

First, we discuss the importance of imaging informatics in pathology and highlight the challenges posed by histopathological WSI. Next, we provide a thorough review of current methods for: quality control of histopathological images; feature extraction that captures image properties at the pixel, object, and semantic levels; predictive modeling that utilizes image features for diagnostic or prognostic applications; and data and information visualization that explores WSI for de novo discovery. In addition, we highlight future research directions and discuss the impact of large public repositories of histopathological data, such as the Cancer Genome Atlas, on the field of pathology informatics. Following the review, we present a case study to illustrate a clinical decision support system that begins with quality control and ends with predictive modeling for several cancer endpoints. Currently, state-of-the-art software tools only provide limited image processing capabilities instead of complete data analysis for clinical decision-making. We aim to inspire researchers to conduct more research in pathology imaging informatics so that clinical decision support can become a reality.     

Diterpene quinone tanshinone IIA selectively inhibits mouse and human cytochrome P4501A2

1. Tanshinone IIA is the main active diterpene quinone in the herbal medicine Salvia miltiorrhiza. In untreated mouse liver microsomes, tanshinone IIA selectively inhibited 7-ethoxyresorufin O -deethylation (EROD) and 7-methoxyresorufin O -demethylation (MROD) activities without affecting the oxidation of benzo(a)pyrene, tolbutamide, N -nitrosodimethylamine and nifedipine. Tanshinone IIA was a competitive inhibitor of MROD activity with a K i of 7.2 ± 0.7 nM. 2. In 3-methylcholanthrene-treated mouse liver microsomes, tanshinone IIA and two minor tanshinones, tanshinone I and cryptotanshinone, inhibited liver microsomal MROD activity without affecting EROD and benzo(a)pyrene hydroxylation activities at the concentrations up to 1 µ M. Tanshinone IIA induced a type I binding spectrum with a spectral dissociation constant K?s of 2.3 ± 0.8 µ M without cooperativity. 3. In human liver microsomes, tanshinone IIA decreased EROD and MROD activities without affecting the oxidation of benzo(a)pyrene, tolbutamide, chlorzoxazone and nifedipine. 4. In Escherichia coli membranes expressing bicistronic human CYP1A enzymes, tanshinone IIA inhibited EROD activity of CYP1A1 with an IC 50 48 times higher than that for CYP1A2. Tanshinone I and cryptotanshinone had the same IC 50 ratio (1A1/1A2) of 4. 5. The results indicate that tanshinone represents a new group of CYP1A inhibitors, and tanshinone IIA had the highest selectivity in inhibition of CYP1A2.     

时间序列预测模型在门诊量预测中的应用

目的应用时间序列预测模型预测门诊量,旨在建立适用医院的门诊量预测方法和预测模型。方法收集某医院2006年一2010年的月门诊量数据,建立时间序列的预测模型,并用该模型进行预测比对。结果该预测模型预测的下一年的前6个月的门诊量非常接近实际门诊量,最大误差仅为1．54％。预测的2011年该院门诊工作量为2,292,594人次。结论运用时间序列预测模型能够取得很好的预测效果,可以为医院管理提供预案和决策依据。     

274例巨大儿临床分析

目的探讨预测巨大儿的相关因素及分娩方式选择,降低母婴并发症。方法回顾分析2010年1—12月在该院分娩的巨大儿274例作为观察组,并随机选取同期分娩的274例正常体重儿作为对照组。结果观察组孕妇在孕周、孕产次、产前体重指数、剖宫产率等明显大于对照组,两组分娩并发症亦有显著差异。结论做好巨大儿的预防,选择合适的分娩方式,有助于减少巨大儿的发生,降低母婴并发症。     

Predicting risk for radiographic damage in rheumatoid arthritis: comparative analysis of the multi-biomarker disease activity score and conventional measures of disease activity in multiple studies

Objective: To compare the multi-biomarker disease activity (MBDA) score with the DAS28-CRP and CRP for predicting risk of radiographic progression in patients with rheumatoid arthritis.

Methods: Published studies of the MBDA score and radiographic progression with ≥100 patients per cohort were evaluated. Rates of radiographic progression over 1?year were determined across the low/moderate/high categories for MBDA score (low/moderate/high: <30, 30–44, >44), DAS28-CRP (low/moderate/high: ≤2.67, >2.67–4.09, >4.09) and CRP (low/moderate/high: ≤10, >10–30, >30?mg/L), with positive and negative predictive value (PPV, NPV) and relative risk (RR) determined for high vs. not-high (i.e. low and moderate combined) categories. Patient-level data from studies having all three measures was pooled to: (1) determine a combined RR for radiographic progression in the high vs. not-high categories for each measure; and (2) compare the predictive ability of MBDA score vs. DAS28-CRP by comparing the rates of radiographic progression observed in subgroups created by cross-classifying the high and not-high categories of each measure.

Results: Five cohorts were identified for inclusion (total N=929). In each, radiographic progression was more frequent with increasing MBDA scores. Among the three cohorts with requisite data, PPVs were generally similar using categories of MBDA score, DAS28-CRP or CRP but NPVs were greater for MBDA score (93–97%) than DAS28-CRP or CRP (77–87%). RRs for radiographic progression were greater when based on categories of MBDA score than DAS28-CRP or CRP and the combined RR was greater for MBDA score (4.6, p?<?.0001) than DAS28-CRP (1.7, p?=?.02) or CRP (1.7, p?=?.002). For patients cross-classified by MBDA score and DAS28-CRP, high vs. not-high MBDA score significantly predicted radiographic progression independently of DAS28-CRP.

Conclusions: High and not-high MBDA scores were associated with increased and low risk, respectively, for radiographic progression over one year. MBDA score was a better predictor of radiographic progression than DAS28-CRP or CRP.     

Effect of Loading Frequency Ratio on Multiaxial Asynchronous Fatigue Failure of 30CrMnSiA Steel

Multiaxial asynchronous fatigue experiments were carried out on 30CrMnSiA steel to investigate the influence of frequency ratio on fatigue crack initiation and propagation. Test results show that the surface cracks initiate on the maximum shear stress amplitude planes with larger normal stress, propagate approximately tens of microns, and then propagate along the maximum normal stress planes. The frequency ratio has an obvious effect on the fatigue life. The variation of normal and shear stress amplitudes on the maximum normal stress plane induces the crack retardation, and results in that the crack growth length is longer for the constant amplitude loading than that for the asynchronous loading under the same fatigue life ratio. A few fatigue life prediction models were employed and compared. Results show that the fatigue life predicted by the model of Bannantine-Socie cycle counting method, section critical plane criterion and Palmgren-Miner’s cumulative damage rule were more applicable.     

MACC1 – a novel target for solid cancers

Introduction: The metastatic dissemination of primary tumors is directly linked to patient survival in many tumor entities. The previously undescribed gene metastasis-associated in colon cancer 1 (MACC1) was discovered by genome-wide analyses in colorectal cancer (CRC) tissues. MACC1 is a tumor stage-independent predictor for CRC metastasis linked to metastasis-free survival.

Areas covered: In this review, the discovery of MACC1 is briefly presented. In the following, the overwhelming confirmation of these data is provided supporting MACC1 as a new remarkable biomarker for disease prognosis and prediction of therapy response for CRC and also for a variety of additional forms of solid cancers. Lastly, the potential clinical utility of MACC1 as a target for prevention or restriction of tumor progression and metastasis is envisioned.

Expert opinion: MACC1 has been identified as a prognostic biomarker in a variety of solid cancers. MACC1 correlated with tumor formation and progression, development of metastases and patient survival representing a decisive driver for tumorigenesis and metastasis. MACC1 was also demonstrated to be of predictive value for therapy response. MACC1 is a promising therapeutic target for anti-tumor and anti-metastatic intervention strategies of solid cancers. Its clinical utility, however, must be demonstrated in clinical trials.