Cost sensitive meta-learning

Classification is one of the primary tasks of data mining and aims to assign a class label to unseen examples by using a model learned from a training dataset. Most of the accepted classifiers are designed to minimize the error rate but in practice data mining involves costs such as the cost of getting the data, and cost of making an error. Hence the following question arises:Among all the available classification algorithms, and in considering a specific type of data and cost, which is the best algorithm for my problem?It is well known to the machine learning community that there is no single algorithm that performs best for all domains. This observation motivates the need to develop an “algorithm selector” which is the work of automating the process of choosing between different algorithms given a specific domain of application. Thus, this research develops a new meta-learning system for recommending cost-sensitive classification methods. The system is based on the idea of applying machine learning to discover knowledge about the performance of different data mining algorithms. It includes components that repeatedly apply different classification methods on data sets and measuring their performance. The characteristics of the data sets, combined with the algorithm and the performance provide the training examples. A decision tree algorithm is applied on the training examples to induce the knowledge which can then be applied to recommend algorithms for new data sets, and then active learning is used to automate the ability to choose the most informative data set that should enter the learning process.This thesis makes contributions to both the fields of meta-learning, and cost sensitive learning in that it develops a new meta-learning approach for recommending cost-sensitive methods. Although, meta-learning is not new, the task of accelerating the learning process remains an open problem, and the thesis develops a novel active learning strategy based on clustering that gives the learner the ability to choose which data to learn from and accordingly, speed up the meta-learning process.Both the meta-learning system and use of active learning are implemented in the WEKA system and evaluated by applying them on different datasets and comparing the results with existing studies available in the literature. The results show that the meta-learning system developed produces better results than METAL, a well-known meta-learning system and that the use of clustering and active learning has a positive effect on accelerating the meta-learning process, where all tested datasets show a decrement of error rate prediction by 75 %

Systematic overview of clinical trials of antiarrhythmic drugs

BACKGROUND Arrhythmia is a cardiovascular disorder which can lead to several complications. Over the past decade the introduction of many new drugs has raised concerns about their questionable benefits and cost-effectiveness. Classification of antiarrhythmic drugs has not been fully resolved. Although numerous clinical trials have been conducted, the value of antiarrhythmic drugs in many indications remains controversial. Two meta-analyses of clinical trials addressing the indication of quinidine (Class I) for maintenance of sinus rhythm after cardioversion have suggested high efficacy rates but increased mortality relative to placebo. Several overviews which were conducted to evaluate the impact of antiarrhythmic therapy on improving survival post acute myocardial infarction, have defined a turning point in the management strategy from Class I to Class III drugs, particularly amiodarone and sotalol, due to the unfavourable mortality outcome with the former Class. MAJOR AIMS This thesis was conducted with three major aims: 1) To assess both qualitatively and quantitatively the benefits and risks associated with flecainide (Class Ic), amiodarone (Class III), and sotalol (Class III & II) in treatment of chronic atrial fibrillation, acute medical or surgical supraventricular arrhythmias, and life-threatening ventricular arrhythmias developing post acute myocardial infarction; 2) To produce an overall summary estimate of effectiveness and probabilities of incidence of adverse effects, which can be useful for subsequent incorporation in cost-effectiveness analysis; 3) To validate the usefulness of various therapeutic outcomes implemented by general treatment guidelines. OVERVIEW OF THESIS A meta-analysis was carried out to compare the efficacy and safety of three antiarrhythmic agents (flecainide, sotalol, and amiodarone) in maintaining sinus rhythm after cardioversion of chronic atrial fibrillation. 42 of 119 clinical trials retrieved satisfied the predefined inclusion criteria. Data from 17 amiodarone trials (5 randomised, and 12 uncontrolled), 8 sotalol trials (6 randomised, and 2 nonrandomised), and 19 flecainide trials (8 randomised, 4 nonrandomised controlled, and 6 uncontrolled) were pooled separately after testing for homogeneity of treatment effect across the trials. Although the pooled rate difference in proportion of patients remaining in sinus rhythm between amiodarone and placebo (2 trials) was statistically nonsignificant (RD3mon = 16.1 %, 95% CI = -29.7 to 61.7, P>0.05), the pooled effect compared to Class IA drugs (3 trials) demonstrated significant differences at all time intervals (RDs were 20.5%, 31 %, and 28.8% at 3, 6, and 12 months respectively). Aggregating sotalol efficacy data in randomised or nonrandomised controlled trials has yielded highly significant effect in favour of sotalol as compared to placebo and equal effect as compared to Class IA and Class IC at all time points. Furthermore, comparison of flecainide to placebo or Class IA has revealed a highly superior effect in favour of flecainide. The calculated summary statistics (ORpeto, ORMH, RD, and RR) for the incidence of mortality and pro arrhythmia in the full-exposure group in amiodarone and sotalol trials were not significant, affirming the safety of those two drugs. In flecainide placebo-controlled trials, the ORMH for mortality and proarrhythmia were 1.8 (95% CI, 1.2-2.7, P=0.002), and (95% CI, 4.23-10.6, P<0.00l) respectively, thus indicating low benefit-risk ratio for flecainide as compared to amiodarone. The validity of this meta-analysis was examined by assessment of publication bias using funnel-plots. A funnel-plot of the amiodarone clinical trials displayed the shape of an 'inverted funnel', thus suggesting an evidence of low retrieval bias. However, due to the small sample size identified (18 trials only), a firm conclusion with regard to absence of publication bias could not be drawn. Evolving strategies for management of newly occurring supraventricular arrhythmias were reviewed. A meta-analysis was undertaken to determine the most effective agent for prompt cardioversion to sinus rhythm. Flecainide efficacy relative to placebo was confirmed by pooling data from 5 placebo-controlled trials (OR3hrs, 7.2; 95% CI, 4.7 to 11.1; Z=8.9; and OR8hrs, 5.5; 95% CI, 3.6 to 8.4; Z=7.85). However, pooling the data from three amiodarone, placebo-controlled trials at 3 and 8 hour-intervals demonstrated a nonsignificant effect (OR3hrs, 1.3; 95% CI, 0.7-2.4; Z=0.85; and OR8hrs, 1.03; 95% CI, 0.6-1.8, Z=0.12). All individual odds ratios for intravenous sotalol compared to placebo were highly significant with pooled OR at 1 hour of 8.8 (95% CI, 4.7-16.5; Z=6.8). The effect sizes of the three agents on mean ventricular response rate was estimated for both converted and unconverted patients. Whilst the effect size of flecainide versus placebo was not statistically significant at any time point, those of sotalol and amiodarone were statistically and clinically meaningful for both converted and unconverted patients. It is suggested that for acute cardioversion, intravenous flecainide or sotalol should be initially implemented. Intravenous amiodarone can be subsequently introduced for controlling the ventricular rate in persistent unconverted patients. Recent meta-analyses of randomised controlled trials of secondary prevention of myocardial infarction by antiarrhythmic agents have questioned the validity of using arrhythmia suppression as a substitutive end point for mortality. A meta-analysis examining the effect of sotalol and amiodarone for prevention of death post acute myocardial infarction was undertaken. In addition to single point estimates of pooled odds ratios of total mortality and sudden death, a meta-analysis of survival data which included censored end points was employed. An attempt was made to reconstruct the life tables in individual trials of amiodarone. The Kaplan-Meier percentages were recalculated and pooled at specific time points to reproduce the final meta-analytic survival curves of total mortality and sudden death. The meta-analysis confirmed the clinical efficacy of amiodarone for prolonging the survival in patients with congestive heart failure or myocardial infarction. The nonparametric log-rank odds ratio method was applied to raw actuarial data deduced from published Kaplan-Meier graphs as well as data generated by curve fitting. Pooling each set of data separately has yielded highly significant log-rank ORs for total mortality in the first set of four trials with censoring (log-rank OR at 102 months, 0.598; 95% CI, 0.43 to 0.83; Z = -3). However, log-rank ORs from data generated by curve fitting of data from a further three trials, were nonsignificant up to 48 months (log-rank OR, 0.87; 95% CI, 0.72 to 1.06, Z = -1.4). Merging of the two data sets has suggested strong evidence of efficacy for improving survival in terms of both total mortality and sudden death

Systematic overview of clinical trials of antiarrhythmic drugs

BACKGROUND Arrhythmia is a cardiovascular disorder which can lead to several complications. Over the past decade the introduction of many new drugs has raised concerns about their questionable benefits and cost-effectiveness. Classification of antiarrhythmic drugs has not been fully resolved. Although numerous clinical trials have been conducted, the value of antiarrhythmic drugs in many indications remains controversial. Two meta-analyses of clinical trials addressing the indication of quinidine (Class I) for maintenance of sinus rhythm after cardioversion have suggested high efficacy rates but increased mortality relative to placebo. Several overviews which were conducted to evaluate the impact of antiarrhythmic therapy on improving survival post acute myocardial infarction, have defined a turning point in the management strategy from Class I to Class III drugs, particularly amiodarone and sotalol, due to the unfavourable mortality outcome with the former Class. MAJOR AIMS This thesis was conducted with three major aims: 1) To assess both qualitatively and quantitatively the benefits and risks associated with flecainide (Class Ic), amiodarone (Class III), and sotalol (Class III & II) in treatment of chronic atrial fibrillation, acute medical or surgical supraventricular arrhythmias, and life-threatening ventricular arrhythmias developing post acute myocardial infarction; 2) To produce an overall summary estimate of effectiveness and probabilities of incidence of adverse effects, which can be useful for subsequent incorporation in cost-effectiveness analysis; 3) To validate the usefulness of various therapeutic outcomes implemented by general treatment guidelines. OVERVIEW OF THESIS A meta-analysis was carried out to compare the efficacy and safety of three antiarrhythmic agents (flecainide, sotalol, and amiodarone) in maintaining sinus rhythm after cardioversion of chronic atrial fibrillation. 42 of 119 clinical trials retrieved satisfied the predefined inclusion criteria. Data from 17 amiodarone trials (5 randomised, and 12 uncontrolled), 8 sotalol trials (6 randomised, and 2 nonrandomised), and 19 flecainide trials (8 randomised, 4 nonrandomised controlled, and 6 uncontrolled) were pooled separately after testing for homogeneity of treatment effect across the trials. Although the pooled rate difference in proportion of patients remaining in sinus rhythm between amiodarone and placebo (2 trials) was statistically nonsignificant (RD3mon = 16.1 %, 95% CI = -29.7 to 61.7, P>0.05), the pooled effect compared to Class IA drugs (3 trials) demonstrated significant differences at all time intervals (RDs were 20.5%, 31 %, and 28.8% at 3, 6, and 12 months respectively). Aggregating sotalol efficacy data in randomised or nonrandomised controlled trials has yielded highly significant effect in favour of sotalol as compared to placebo and equal effect as compared to Class IA and Class IC at all time points. Furthermore, comparison of flecainide to placebo or Class IA has revealed a highly superior effect in favour of flecainide. The calculated summary statistics (ORpeto, ORMH, RD, and RR) for the incidence of mortality and pro arrhythmia in the full-exposure group in amiodarone and sotalol trials were not significant, affirming the safety of those two drugs. In flecainide placebo-controlled trials, the ORMH for mortality and proarrhythmia were 1.8 (95% CI, 1.2-2.7, P=0.002), and (95% CI, 4.23-10.6, P<0.00l) respectively, thus indicating low benefit-risk ratio for flecainide as compared to amiodarone. The validity of this meta-analysis was examined by assessment of publication bias using funnel-plots. A funnel-plot of the amiodarone clinical trials displayed the shape of an 'inverted funnel', thus suggesting an evidence of low retrieval bias. However, due to the small sample size identified (18 trials only), a firm conclusion with regard to absence of publication bias could not be drawn. Evolving strategies for management of newly occurring supraventricular arrhythmias were reviewed. A meta-analysis was undertaken to determine the most effective agent for prompt cardioversion to sinus rhythm. Flecainide efficacy relative to placebo was confirmed by pooling data from 5 placebo-controlled trials (OR3hrs, 7.2; 95% CI, 4.7 to 11.1; Z=8.9; and OR8hrs, 5.5; 95% CI, 3.6 to 8.4; Z=7.85). However, pooling the data from three amiodarone, placebo-controlled trials at 3 and 8 hour-intervals demonstrated a nonsignificant effect (OR3hrs, 1.3; 95% CI, 0.7-2.4; Z=0.85; and OR8hrs, 1.03; 95% CI, 0.6-1.8, Z=0.12). All individual odds ratios for intravenous sotalol compared to placebo were highly significant with pooled OR at 1 hour of 8.8 (95% CI, 4.7-16.5; Z=6.8). The effect sizes of the three agents on mean ventricular response rate was estimated for both converted and unconverted patients. Whilst the effect size of flecainide versus placebo was not statistically significant at any time point, those of sotalol and amiodarone were statistically and clinically meaningful for both converted and unconverted patients. It is suggested that for acute cardioversion, intravenous flecainide or sotalol should be initially implemented. Intravenous amiodarone can be subsequently introduced for controlling the ventricular rate in persistent unconverted patients. Recent meta-analyses of randomised controlled trials of secondary prevention of myocardial infarction by antiarrhythmic agents have questioned the validity of using arrhythmia suppression as a substitutive end point for mortality. A meta-analysis examining the effect of sotalol and amiodarone for prevention of death post acute myocardial infarction was undertaken. In addition to single point estimates of pooled odds ratios of total mortality and sudden death, a meta-analysis of survival data which included censored end points was employed. An attempt was made to reconstruct the life tables in individual trials of amiodarone. The Kaplan-Meier percentages were recalculated and pooled at specific time points to reproduce the final meta-analytic survival curves of total mortality and sudden death. The meta-analysis confirmed the clinical efficacy of amiodarone for prolonging the survival in patients with congestive heart failure or myocardial infarction. The nonparametric log-rank odds ratio method was applied to raw actuarial data deduced from published Kaplan-Meier graphs as well as data generated by curve fitting. Pooling each set of data separately has yielded highly significant log-rank ORs for total mortality in the first set of four trials with censoring (log-rank OR at 102 months, 0.598; 95% CI, 0.43 to 0.83; Z = -3). However, log-rank ORs from data generated by curve fitting of data from a further three trials, were nonsignificant up to 48 months (log-rank OR, 0.87; 95% CI, 0.72 to 1.06, Z = -1.4). Merging of the two data sets has suggested strong evidence of efficacy for improving survival in terms of both total mortality and sudden death

Feature selection in meta learning framework

Feature selection is a key step in data mining. Unfortunately, there is no single feature selection method that is always the best and the data miner usually has to experiment with different methods using a trial and error approach, which can be time consuming and costly especially with very large datasets. Hence, this research aims to develop a meta learning framework that is able to learn about which feature selection methods work best for a given data set. The framework involves obtaining the characteristics of the data and then running alternative feature selection methods to obtain their performance. The characteristics, methods used and their performance provide the examples which are used by a learner to induce the meta knowledge which can then be applied to predict future performance on unseen data sets

Drug standardization through pharmacognostic approaches and estimation of anticancer potential of chamomile (Matricaria chamomilla L.) using prostate-cancer cell lines : an in-vitro study

Cancer is the major challenge across world and the adenocarcinoma of prostate malignancy is the second most prevalent male cancer. Various medicinal plants are used for the treatment and management of various cancers. Matricaria chamomilla L., is one of the extensively used Unani medicament for the treatment of various type of diseases. In the current study we evaluated most of the parameters prescribed for drug standardization using pharmacognostic approaches. The 2,2 Diphenyl-1-picryl hydrazyl (DPPH) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. Moreover, we analyzed the antioxidant and cytotoxic activity of M. chamomilla (Gul-e Babuna) through in-vitro method. DPPH (2,2-diphenyl-1-picryl-hydrazl-hydrate) method was utilized for the analysis of antioxidant activity in the flower extracts of M. chamomilla. CFU and wound healing assay were performed to determine the anti-cancer activity. The results demonstrated that various extracts of M. chamomilla fulfilled most of the parameters of drug standardization and contained good antioxidant and anticancer activities. The ethyl acetate showed higher anticancer activity followed by aqueous, hydroalcoholic, petroleum benzene and methanol by CFU method. Also, the wound healing assay demonstrated that ethyl acetate extract has more significant effect followed by methanol and petroleum benzene extract on prostate cancer cell line (C4-2). The current study concluded that the extract of M. chamomilla flowers could act as good source of natural anti-cancer compounds.CCRUM, New Delhi; Science and Engineering Research Board, Department of Science and Technology, Government of India; SERB research grant; Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; South African Medical Research Council (SAMRC) and the National Research Foundation (NRF).https://www.jcancer.orgam2024Medical OncologySDG-03:Good heatlh and well-bein

Corrigendum: A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures

Abstract Background Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax® and Fosamax® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel® and Actonel Once a Week®, Warner Chilcott UK Ltd), ibandronic acid (Bonviva®, Roche Products Ltd) and zoledronic acid (Aclasta®, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. Data sources For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. Review methods A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. Results Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. Limitations We assumed that all treatment strategies are viable alternatives across the whole population. Conclusions Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. Study registration This study is registered as PROSPERO CRD42013006883. Funding The National Institute for Health Research Health Technology Assessment programme