Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants versus Vitamin K Antagonist Oral Anticoagulants in Patients Undergoing Radiofrequency Catheter Ablation of Atrial Fibrillation: A Meta-Analysis

BackgroundUse of the non-vitamin K antagonist oral anticoagulants (NOACs) is endorsed by current guidelines for stroke prevention in patients with atrial fibrillation (AF). However efficacy and safety of NOACs in patients undergoing catheter ablation (RFCA) of AF has not been well established yet.ObjectivesTo perform a meta-analysis of all studies comparing NOACs and vitamin K antagonist oral anticoagulants (VKAs) in patients undergoing RFCA.ResultsThere was no significant difference in thromboembolic complications (RR 1.39; p=0.13). Bleeding complications were significantly lower in the NOACs-treated arm as compared to VKAs (RR=0.67, p<0.001). Interestingly, a larger number of thromboembolic events was found in the VKAs-treated arm in those studies where VKAs had been interrupted during the periprocedural phase (RR=0.68; p=ns). In this same subgroup a significantly higher incidence of both minor (RR=0.54; p=0.002) and major bleeding (RR=0.41; p=0.01) events was recorded. Conversely, the incidence of thromboembolic events in the VKAs-treated arm was significantly lower in those studies with uninterrupted periprocedural anticoagulation treatment (RR=1.89; p=0.02).LimitationsAs with every meta-analysis, no patients-level data were available.

Conclusions and Implications

The use of NOACs in patients undergoing RFCA is safe, given the lower incidence of bleedings observed with NOACs. On the other side, periprocedural interruption of VKAs and bridging with heparin is associated with a higher bleeding rate with no significant benefit on onset of thromboembolic events.     

A Role for the Superior Colliculus in Decision Criteria

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Decision Analysis Utilizing Data from Multiple Life-Cycle Impact Assessment Methods Part I: A Theoretical Basis

Numerous methodologies for the life-cycle impact assessment (LCIA) step of life-cycle assessment (LCA) are currently in popular use. These methods, which are based on a single method or level of analysis, are limited to the environmental fates, impact categories, damage functions, and stressors included in the method or model. Because of this, it has been suggested within the LCA community that LCIA data from multiple methods and/or levels of analysis, that is, end-point and midpoint indicators, be used in LCA-based decision analysis to facilitate better or, at least more informed, decision making. In this (two-part) series of articles, we develop and present a series of LCA-based decision analysis models, based on multiattribute value theory (MAVT), which utilize data from multiple LCIA methods and/or levels of analysis. The key to accomplishing this is the recognition of what LCIA damage indicators represent with respect to decision analysis, namely, decision attributes and, in most cases, proxy attributes. The use of proxy attributes in a decision model, however, poses certain challenges, such as the assessment of decision-maker preferences for actual consequences that are only known imprecisely because of inherent limits of both LCA and scientific knowledge. In this article (part I), we provide a brief overview of MAVT and examine some of the decision-theoretic issues and implications of current LCIA methods. We illustrate the application of MAVT to develop a decision model utilizing damage indicators from a single LCIA methodology; and, we identify the decision-theoretic issues that arise when attempting to combine LCIA indicators from multiple methods and/or levels of analysis in a single decision model. Finally, we introduce the use in our methodology of constructed attributes to combine related end-point damage indicators into single decision attributes and the concept and evaluation of proxy attributes.     

Clinical Verification of A Clinical Decision Support System for Ventilator Weaning

Background

Weaning is typically regarded as a process of discontinuing mechanical ventilation in the daily practice of an intensive care unit (ICU). Among the ICU patients, 39%-40% need mechanical ventilator for sustaining their lives. The predictive rate of successful weaning achieved only 35-60% for decisions made by physicians. Clinical decision support systems (CDSSs) are promising in enhancing diagnostic performance and improve healthcare quality in clinical setting. To our knowledge, a prospective study has never been conducted to verify the effectiveness of the CDSS in ventilator weaning before. In this study, the CDSS capable of predicting weaning outcome and reducing duration of ventilator support for patients has been verified.

Methods

A total of 380 patients admitted to the respiratory care center of the hospital were randomly assigned to either control or study group. In the control group, patients were weaned with traditional weaning method, while in the study group, patients were weaned with CDSS monitored by physicians. After excluding the patients who transferred to other hospitals, refused further treatments, or expired the admission period, data of 168 and 144 patients in the study and control groups, respectively, were used for analysis.

Results

The results show that a sensitivity of 87.7% has been achieved, which is significantly higher (p<0.01) than the weaning determined by physicians (sensitivity: 61.4%). Furthermore, the days using mechanical ventilator for the study group (38.41 ± 3.35) is significantly (p<0.001) shorter than the control group (43.69 ± 14.89), with a decrease of 5.2 days in average, resulting in a saving of healthcare cost of NT$45,000 (US$1,500) per patient in the current Taiwanese National Health Insurance setting.

Conclusions

The CDSS is demonstrated to be effective in identifying the earliest time of ventilator weaning for patients to resume and sustain spontaneous breathing, thereby avoiding unnecessary prolonged ventilator use and decreasing healthcare cost.

     

Decision Analysis: A Method for Taking Uncertainties into Account in Risk-Based Decision Making

The assessment of human and ecological risks and associated risk-management decisions are characterized by only partial knowledge of the relevant systems. Typically, large variability and measurement errors in data create challenges for estimating risks and identifying appropriate management strategies. The formal quantitative method of decision analysis can help deal with these challenges because it takes uncertainties into account explicitly and quantitatively. In recent years, research in several areas of natural resource management has demonstrated that decision analysis can identify policies that are appropriate in the presence of uncertainties. More importantly, the resulting optimal decision is often different from the one that would have been chosen had the uncertainties not been taken into account quantitatively. However, challenges still exist to effective implementation of decision analysis.     

Risk of Fatal Bleeding in Episodes of Major Bleeding with New Oral Anticoagulants and Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Background

The reversibility of new/novel oral anticoagulants (NOAC) is not well understood, whereas the reversal strategies for bleeding associated with vitamin k antagonists (VKA), such as warfarin, is well established. It is unknown whether outcomes are different between bleeds occurring with NOAC compared to VKA use.

Objectives

This systematic review and meta-analysis of randomized controlled trials determines the relative odds of fatal bleeding given that a patient suffered a major bleed while on NOAC versus VKA therapy.

Search Methods

Data on major and fatal bleeding events was sought from randomized controlled trials of NOAC agents compared to VKAs.

Main Results

20 trials were included in the meta-analysis. From which, 4056 first-time, major bleeding events were reported and included in the primary analysis. The summary odds ratio for the conditional odds of fatal bleeding given that a major bleeding event occurred was 0.65 [0.52, 0.81] favoring the NOAC agents (p = 0.0001). The reduced odds of fatal bleeding with NOACs was not demonstrated after controlling for bleeding location. Given that an intracranial bleeding event occurred, the summary odds ratio for the conditional odds of fatal bleeding was 0.96 [0.70, 1.32]. For extracranial bleeding events, the summary odds ratio was also statistically insignificant at 0.945 [0.66, 1.35].

Author’s Conclusions

The odds ratio calculated in this meta-analysis showed a reduced odds of death in major bleeding associated with NOAC use. This risk reduction was due to a disproportionate amount of intracranial bleeding in the VKA arms. For any given bleeding site, there was no evidence of a significant difference in fatal outcomes from bleeds associated with NOAC versus VKA use.

Protocol Registration

Protocol registered on PROSPERO under CRD42014013294.     

基于多目标的杨树速生丰产林主伐决策分析

经济效益综合评价是产业决策研究的重要内容.从系统工程观点来看,经济效益综合评价本质上是一个有限方案多目标决策问题.因此,本文采用多目标决策法对杨树速生丰产林的主伐决策进行研究,以年均净现值、内部收益率、土地期望价、效益成本比、成本利润率为指标,提出用熵技术法确定评价指标权重,结合"理想点"法、TOPSIS法和线性加权和法三种方法对决策方案进行排序择优,得到不同排序结果,最后用平均值法得到最终综合评价结果.结果表明,对所研究的密度为10×10m~2、8×8m~2、6×8m~2、5×6m~2的杨速生丰产林进行分析得到综合评价结果,其最优主伐龄分别为:13年、10年、9年、9年.随着密度的增大,经济成熟龄提前.本研究表明该方法对杨树速生丰产林的主伐决策研究是有效可行的.     

两种药物性肝炎诊断评分标准的临床应用分析

目的:比较Maria药物性肝损害(1997年)诊断标准和我国常用诊断标准对药物性肝损害的效价。方法:回顾性分析我院2005年1月至2006年4月期间经肝穿病理诊断为药物性肝损害的54例病例,分别按照上述两个标准评分。评价每一标准的准确性。结果:符合Maria药物性肝损害(1997年)诊断标准的(>10分)有45例,占83%;符合我国常用诊断标准的有39例,占72%。结论:两个诊断标准符合率较高,均可做为药物性肝损害的诊断标准,但仍有部分病例不能准确诊断,需进一步完善。     

Aggregation in a Desert Tenebrionid Beetle: A Cost/Benefit Analysis

Parastizopus armaticeps (Coleoptera: Tenebrionidae), a nocturnal fossorial detritivore inhabiting southern Kalahari dunes, aggregates in burrows during the day. Group size increases during drought but 25% of beetles are still found alone or in pairs. During drought, beetles from large groups leave burrows after sunset synchronously and carlier than pairs and single animals and earlier than beetles of any group size after rain. Detritus from the beetles' major foodplant is scarce and food competition high. Beetles emerging early preferentially select and carry high-quality transportable items into burrows to eat (forage); late-emerging ones feed on the low-quality large twigs on the surface. Foraging is shown to be a strategy to secure food items against surface competitors, not one to reduce body water loss during surface exposure. The costs and benefits of group vs. solitary lifestyles and alternate hypotheses for early and synchronous emergence were tested experimentally. Grouped beetles had lower body water loss rates but, due to competition with burrow mates, higher feeding costs than single ones. It is hunger that advances and thus synchronizes emergence time, not social facilitation. Field data support a model predicting that, for maximal benefits, beetles should alternate between solitary and group life at optimal time intervals.     

Potential Cost-Effectiveness of a New Infant Tuberculosis Vaccine in South Africa - Implications for Clinical Trials: A Decision Analysis

Novel tuberculosis vaccines are in varying stages of pre-clinical and clinical development. This study seeks to estimate the potential cost-effectiveness of a BCG booster vaccine, while accounting for costs of large-scale clinical trials, using the MVA85A vaccine as a case study for estimating potential costs. We conducted a decision analysis from the societal perspective, using a 10-year time frame and a 3% discount rate. We predicted active tuberculosis cases and tuberculosis-related costs for a hypothetical cohort of 960,763 South African newborns (total born in 2009). We compared neonatal vaccination with bacille Calmette-Guérin alone to vaccination with bacille Calmette-Guérin plus a booster vaccine at 4 months. We considered booster efficacy estimates ranging from 40% to 70%, relative to bacille Calmette-Guérin alone. We accounted for the costs of Phase III clinical trials. The booster vaccine was assumed to prevent progression to active tuberculosis after childhood infection, with protection decreasing linearly over 10 years. Trial costs were prorated to South Africa''s global share of bacille Calmette-Guérin vaccination. Vaccination with bacille Calmette-Guérin alone resulted in estimated tuberculosis-related costs of $89.91 million 2012 USD, and 13,610 tuberculosis cases in the birth cohort, over the 10 years. Addition of the booster resulted in estimated cost savings of $7.69–$16.68 million USD, and 2,800–4,160 cases averted, for assumed efficacy values ranging from 40%–70%. A booster tuberculosis vaccine in infancy may result in net societal cost savings as well as fewer active tuberculosis cases, even if efficacy is relatively modest and large scale Phase III studies are required.     

Better Informing Decision Making with Multiple Outcomes Cost-Effectiveness Analysis under Uncertainty in Cost-Disutility Space

Introduction

Comparing multiple, diverse outcomes with cost-effectiveness analysis (CEA) is important, yet challenging in areas like palliative care where domains are unamenable to integration with survival. Generic multi-attribute utility values exclude important domains and non-health outcomes, while partial analyses—where outcomes are considered separately, with their joint relationship under uncertainty ignored—lead to incorrect inference regarding preferred strategies.

Objective

The objective of this paper is to consider whether such decision making can be better informed with alternative presentation and summary measures, extending methods previously shown to have advantages in multiple strategy comparison.

Methods

Multiple outcomes CEA of a home-based palliative care model (PEACH) relative to usual care is undertaken in cost disutility (CDU) space and compared with analysis on the cost-effectiveness plane. Summary measures developed for comparing strategies across potential threshold values for multiple outcomes include: expected net loss (ENL) planes quantifying differences in expected net benefit; the ENL contour identifying preferred strategies minimising ENL and their expected value of perfect information; and cost-effectiveness acceptability planes showing probability of strategies minimising ENL.

Results

Conventional analysis suggests PEACH is cost-effective when the threshold value per additional day at home ( ₁) exceeds $1,068 or dominated by usual care when only the proportion of home deaths is considered. In contrast, neither alternative dominate in CDU space where cost and outcomes are jointly considered, with the optimal strategy depending on threshold values. For example, PEACH minimises ENL when ₁=$2,000 and ₂=$2,000 (threshold value for dying at home), with a 51.6% chance of PEACH being cost-effective.

Conclusion

Comparison in CDU space and associated summary measures have distinct advantages to multiple domain comparisons, aiding transparent and robust joint comparison of costs and multiple effects under uncertainty across potential threshold values for effect, better informing net benefit assessment and related reimbursement and research decisions.     

A Review of Clinical Radioprotection and Chemoprotection for Oral Mucositis

The first tenet of medicine, “primum non nocere” or “first, do no harm”, is not always compatible with oncological interventions e.g., chemotherapy, targeted therapy and radiation, since they commonly result in significant toxicities. One of the more frequent and serious treatment-induced toxicities is mucositis and particularly oral mucositis (OM) described as inflammation, atrophy and breakdown of the mucosa or lining of the oral cavity. The sequelae of oral mucositis (OM), which include pain, odynodysphagia, dysgeusia, decreased oral intake and systemic infection, frequently require treatment delays, interruptions and discontinuations that not only negatively impact quality of life but also tumor control and survivorship. One potential strategy to reduce or prevent the development of mucositis, for which no effective therapies exist only best supportive empirical care measures, is the administration of agents referred to as radioprotectors and/or chemoprotectors, which are intended to differentially protect normal but not malignant tissue from cytotoxicity. This limited-scope review briefly summarizes the incidence, pathogenesis, symptoms and impact on patients of OM as well as the background and mechanisms of four clinical stage radioprotectors/chemoprotectors, amifostine, palifermin, GC4419 and RRx-001, with the proven or theoretical potential to minimize the development of mucositis particularly in the treatment of head and neck cancers.     

Drug Repurposing: A Systematic Approach to Evaluate Candidate Oral Neuroprotective Interventions for Secondary Progressive Multiple Sclerosis

Objective

To develop and implement an evidence based framework to select, from drugs already licenced, candidate oral neuroprotective drugs to be tested in secondary progressive multiple sclerosis.

Design

Systematic review of clinical studies of oral putative neuroprotective therapies in MS and four other neurodegenerative diseases with shared pathological features, followed by systematic review and meta-analyses of the in vivo experimental data for those interventions. We presented summary data to an international multi-disciplinary committee, which assessed each drug in turn using pre-specified criteria including consideration of mechanism of action.

Results

We identified a short list of fifty-two candidate interventions. After review of all clinical and pre-clinical evidence we identified ibudilast, riluzole, amiloride, pirfenidone, fluoxetine, oxcarbazepine, and the polyunsaturated fatty-acid class (Linoleic Acid, Lipoic acid; Omega-3 fatty acid, Max EPA oil) as lead candidates for clinical evaluation.

Conclusions

We demonstrate a standardised and systematic approach to candidate identification for drug rescue and repurposing trials that can be applied widely to neurodegenerative disorders.