Using decision-tree classifier systems to extract knowledge from databases

One difficulty in applying artificial intelligence techniques to the solution of real world problems is that the development and maintenance of many AI systems, such as those used in diagnostics, require large amounts of human resources. At the same time, databases frequently exist which contain information about the process(es) of interest. Recently, efforts to reduce development and maintenance costs of AI systems have focused on using machine learning techniques to extract knowledge from existing databases. Research is described in the area of knowledge extraction using a class of machine learning techniques called decision-tree classifier systems. Results of this research suggest ways of performing knowledge extraction which may be applied in numerous situations. In addition, a measurement called the concept strength metric (CSM) is described which can be used to determine how well the resulting decision tree can differentiate between the concepts it has learned. The CSM can be used to determine whether or not additional knowledge needs to be extracted from the database. An experiment involving real world data is presented to illustrate the concepts described

Strategies for adding adaptive learning mechanisms to rule-based diagnostic expert systems

Rule-based diagnostic expert systems can be used to perform many of the diagnostic chores necessary in today's complex space systems. These expert systems typically take a set of symptoms as input and produce diagnostic advice as output. The primary objective of such expert systems is to provide accurate and comprehensive advice which can be used to help return the space system in question to nominal operation. The development and maintenance of diagnostic expert systems is time and labor intensive since the services of both knowledge engineer(s) and domain expert(s) are required. The use of adaptive learning mechanisms to increment evaluate and refine rules promises to reduce both time and labor costs associated with such systems. This paper describes the basic adaptive learning mechanisms of strengthening, weakening, generalization, discrimination, and discovery. Next basic strategies are discussed for adding these learning mechanisms to rule-based diagnostic expert systems. These strategies support the incremental evaluation and refinement of rules in the knowledge base by comparing the set of advice given by the expert system (A) with the correct diagnosis (C). Techniques are described for selecting those rules in the in the knowledge base which should participate in adaptive learning. The strategies presented may be used with a wide variety of learning algorithms. Further, these strategies are applicable to a large number of rule-based diagnostic expert systems. They may be used to provide either immediate or deferred updating of the knowledge base

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

Outcomes After Cardioversion and Atrial Fibrillation Ablation in Patients Treated With Rivaroxaban and Warfarin in the ROCKET AF Trial

ObjectivesThis study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban.BackgroundThere are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors.MethodsWe compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial.ResultsOver a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups.ConclusionsDespite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation [ROCKET AF]; NCT00403767

Impact of global geographic region on time in therapeutic range on warfarin anticoagulant therapy:data from the ROCKET AF clinical trial

Background: Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results: TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR 3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions: Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing

Safety and Efficacy of Rivaroxaban in Patients With Cardiac Implantable Electronic Devices:Observations From the ROCKET AF Trial

Background: Although implantation of cardiac implantable electronic devices (CIEDs) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting. Methods and Results: Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision. In this post‐hoc, postrandomization, on‐treatment analysis, only the first intervention per patient was analyzed. During a median follow‐up of 2.2 years, 453 patients (242 rivaroxaban group; 211 warfarin group) underwent de novo CIED implantation (64.2%) or revision procedures (35.8%). Patients who received CIEDs were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive CIEDs. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30‐day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing. Conclusions: Bleeding and thromboembolic events were low in both rivaroxaban‐ and warfarin‐treated patients. Periprocedural use of oral factor Xa inhibitors in CIED implantation requires further study in prospective, randomized trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767

Hospitalizations in patients with atrial fibrillation:an analysis from ROCKET AF

AIMS: The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF. METHODS AND RESULTS: The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29–1.66], diabetes [1.22, (1.11–1.34)], prior MI [1.27, (1.13–1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04–1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization. CONCLUSION: Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization

Antiplatelet Therapy After Noncardioembolic Stroke

Background and Purpose- We assessed the efficacy and safety of antiplatelet agents after noncardioembolic stroke or transient ischemic attack and examined how these vary according to patients' demographic and clinical characteristics. Methods- We did a network meta-analysis (NMA) of data from 6 randomized trials of the effects of commonly prescribed antiplatelet agents in the long-term (≥3 months) secondary prevention of noncardioembolic stroke or transient ischemic attack. Individual patient data from 43 112 patients were pooled and reanalyzed. Main outcomes were serious vascular events (nonfatal stroke, nonfatal myocardial infarction, or vascular death), major bleeding, and net clinical benefit (serious vascular event or major bleeding). Subgroup analyses were done according to age, sex, ethnicity, hypertension, qualifying diagnosis, type of vessel involved (large versus small vessel disease), and time from qualifying event to randomization. Results- Aspirin/dipyridamole combination (RRNMA-adj, 0.83; 95% CI, 0.74-0.94) significantly reduced the risk of vascular events compared with aspirin, as did clopidogrel (RRNMA-adj, 0.88; 95% CI, 0.78-0.98), and aspirin/clopidogrel combination (RRNMA-adj, 0.83; 95% CI, 0.71-0.96). Clopidogrel caused significantly less major bleeding and intracranial hemorrhage than aspirin, aspirin/dipyridamole combination, and aspirin/clopidogrel combination. Aspirin/clopidogrel combination caused significantly more major bleeding than aspirin, aspirin/dipyridamole combination, and clopidogrel. Net clinical benefit was similar for clopidogrel and aspirin/dipyridamole combination (RRNMA-adj, 0.99; 95% CI, 0.93-1.05). Subgroup analyses showed no heterogeneity of treatment effectiveness across prespecified su

Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial

Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion: In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF