A systematic comparison of software dedicated to meta-analysis of causal studies

<p>Abstract</p> <p>Background</p> <p>Our objective was to systematically assess the differences in features, results, and usability of currently available meta-analysis programs.</p> <p>Methods</p> <p>Systematic review of software. We did an extensive search on the internet (Google, Yahoo, Altavista, and MSN) for specialized meta-analysis software. We included six programs in our review: Comprehensive Meta-analysis (CMA), MetAnalysis, MetaWin, MIX, RevMan, and WEasyMA. Two investigators compared the features of the software and their results. Thirty independent researchers evaluated the programs on their usability while analyzing one data set.</p> <p>Results</p> <p>The programs differed substantially in features, ease-of-use, and price. Although most results from the programs were identical, we did find some minor numerical inconsistencies. CMA and MIX scored highest on usability and these programs also have the most complete set of analytical features.</p> <p>Conclusion</p> <p>In consideration of differences in numerical results, we believe the user community would benefit from openly available and systematically updated information about the procedures and results of each program's validation. The most suitable program for a meta-analysis will depend on the user's needs and preferences and this report provides an overview that should be helpful in making a substantiated choice.</p

Development and validation of MIX: comprehensive free software for meta-analysis of causal research data

BACKGROUND: Meta-analysis has become a well-known method for synthesis of quantitative data from previously conducted research in applied health sciences. So far, meta-analysis has been particularly useful in evaluating and comparing therapies and in assessing causes of disease. Consequently, the number of software packages that can perform meta-analysis has increased over the years. Unfortunately, it can take a substantial amount of time to get acquainted with some of these programs and most contain little or no interactive educational material. We set out to create and validate an easy-to-use and comprehensive meta-analysis package that would be simple enough programming-wise to remain available as a free download. We specifically aimed at students and researchers who are new to meta-analysis, with important parts of the development oriented towards creating internal interactive tutoring tools and designing features that would facilitate usage of the software as a companion to existing books on meta-analysis. RESULTS: We took an unconventional approach and created a program that uses Excel as a calculation and programming platform. The main programming language was Visual Basic, as implemented in Visual Basic 6 and Visual Basic for Applications in Excel 2000 and higher. The development took approximately two years and resulted in the 'MIX' program, which can be downloaded from the program's website free of charge. Next, we set out to validate the MIX output with two major software packages as reference standards, namely STATA (metan, metabias, and metatrim) and Comprehensive Meta-Analysis Version 2. Eight meta-analyses that had been published in major journals were used as data sources. All numerical and graphical results from analyses with MIX were identical to their counterparts in STATA and CMA. The MIX program distinguishes itself from most other programs by the extensive graphical output, the click-and-go (Excel) interface, and the educational features. CONCLUSION: The MIX program is a valid tool for performing meta-analysis and may be particularly useful in educational environments. It can be downloaded free of charge via or

Does CDX2 expression predict Barrett's metaplasia in oesophageal columnar epithelium without goblet cells?

Background: Intestinal metaplasia (Barrett's oesophagus), but not cardiac-type mucosa in columnar-lined oesophagus, is regarded as premalignant. As intestinal metaplasia and cardiac-type mucosa are endoscopically indiscernible, it is difficult to take targeted samples from columnar-lined oesophagus with consequently a risk of having undetected intestinal metaplasia. Aim: To investigate whether the intestinal markers CDX2, MUC2 and villin can predict the presence of undetected intestinal metaplasia in columnar-lined oesophagus. Methods: Presence of intestinal metaplasia or cardiac-type mucosa was identified in 122 biopsy sets of columnar-lined oesophagus from 61 patients, collected at two subsequent follow-up upper endoscopies. CDX2, MUC2 and villin expression were determined by immunohistochemistry. Results: All intestinal metaplasia samples (55) were positive for CDX2 and MUC2 and 32 of 55 for vil

Aortic Stenosis and Heart Failure: Disease Ascertainment and Statistical Considerations for Clinical Trials

Aortic stenosis is a progressive disease that develops over decades, and once symptomatic and untreated, is associated with poor survival. Transcatheter aortic valve replacement has evolved significantly in the past decade and has expanded its indication from surgically inoperable and high-risk patients to patients with intermediate risk. Assessment of heart failure-related outcomes include the use of functional assessments, disease-specific quality of life surveys and standardised ascertainment of events, such as hospitalisations. Multiple statistical approaches are currently being tested to account for recurrent events such as hospitalisations for heart failure or to combine binary and continuous outcomes, both intended to assess the holistic burden of the disease, as opposed to the traditional analysis of time to first event

Discordant severity criteria in patients with moderate aortic stenosis: prognostic implications

Background The criteria to define the grade of aortic stenosis (AS)-aortic valve area (AVA) and mean gradient (MG) or peak jet velocity-do not always coincide into one grade. Although in severe AS, this discrepancy is well characterised, in moderate AS, the phenomenon of discordant grading has not been investigated and its prognostic implications are unknown.Objectives To investigate the occurrence of discordant grading in patients with moderate AS (defined by an AVA between 1.0 cm(2) and 1.5 cm(2) but with an MG = 20 mm Hg) in terms of clinical outcomes.Methods From an ongoing registry of patients with AS, patients with moderate AS based on AVA were selected and classified into discordant or concordant grading (MG = 20 mm Hg, respectively). The clinical endpoint was all-cause mortality.Results Of 790 patients with moderate AS, 150 (19.0%) had discordant grading, moderate AS. Patients with discordant grading were older, had higher prevalence of previous myocardial infarction and left ventricular (LV) hypertrophy, larger LV end-diastolic and end-systolic volume index, higher LV filling pressure and lower LV ejection fraction and stroke volume index as compared with their counterparts. After a median follow-up of 4.9 years (IQR 3.0-8.2), patients with discordant grading had lower aortic valve replacement rates (26.7% vs 44.1%, p<0.001) and higher mortality rates (60.0% vs 43.1%, p<0.001) as compared with patients with concordant grading. Discordant grading moderate AS, combined with low LV ejection fraction, presented the higher risk of mortality (HR 2.78 (2.00-3.87), p<0.001).Conclusion Discordant-grading moderate AS is not uncommon and, when combined with low LV ejection fraction, is associated with high risk of mortality.Cardiolog

Impact of tricuspid regurgitation on survival in patients with heart failure: a large electronic health record patient-level database analysis.

AIMS: More evidence is needed to quantify the association between tricuspid regurgitation (TR) and mortality in patients with heart failure (HF). METHODS AND RESULTS: Between 2008-2017, using the Optum longitudinal database, a patient-level database that integrates multiple US-based electronic health and claim records from several health care providers, we identified 435 679 patients with new HF diagnosis and both an assessment of the left ventricular ejection fraction and at least 1 year of history. TR was graded as mild, moderate or severe and classified as prevalent (at the time of the initial HF diagnosis) or incident (subsequent new cases thereafter). For prevalent TR, the analysis was performed using a Cox proportional hazards model with adjustment for patient covariates. Incident TR was modelled as a time-updated covariate, as were other non-fatal events during follow-up. Prevalence of mild, moderate and severe TR at baseline was 10.1%, 5.1% and 1.4%, respectively. Over a median follow-up of 1.5 years, 121 273 patients (27.8%) died and prevalent TR was independently associated with survival. Compared to patients with no TR at baseline, the adjusted hazard ratios for mortality were 0.99 [95% confidence interval (CI) 0.97-1.01], 1.17 (95% CI 1.14-1.20) and 1.34 (95% CI 1.28-1.39) for mild, moderate and severe TR, respectively. In the 363 270 patients free from TR at baseline, incident TR (at least mild, at least moderate, or severe) developed during follow-up in 12.1%, 5.1% and 1.1%, respectively. Adjusted mortality hazard ratios for such new cases were 1.48 (95% CI 1.44-1.52), 1.92 (95% CI 1.86-1.99) and 2.44 (95% CI 2.32-2.57), respectively. Findings were consistent across all patient subgroups based on age, gender, rhythm, associated comorbidities, prior cardiac surgery, B-type natriuretic peptide/N-terminal pro-B-type natriuretic peptide, and left ventricular ejection fraction. CONCLUSIONS: In this large contemporary patient-level database of almost half-million US patients with HF, TR was associated with a marked increases in mortality risk overall and in all subgroups. Future randomized controlled trials will evaluate the impact of TR correction on clinical outcomes and the causal relationship between TR and mortality

Prosthesis-patient mismatch after aortic valve replacement in the PARTNER 2 trial and registry

Objectives This study aimed to compare incidence and impact of measured prosthesis-patient mismatch (PPMM) versus predicted PPM (PPMP) after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). Background TAVR studies have used measured effective orifice area indexed (EOAi) to body surface area (BSA) to define PPM, but most SAVR series have used predicted EOAi. This difference may contribute to discrepancies in incidence and outcomes of PPM between series. Methods The study analyzed SAVR patients from the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial and TAVR patients from the PARTNER 2 SAPIEN 3 Intermediate Risk registry. PPM was classified as moderate if EOAi ≤0.85 cm2/m2 (≤0.70 if obese: body mass index ≥30 kg/m2) and severe if EOAi ≤0.65 cm2/m2 (≤0.55 if obese). PPMM was determined by the core lab–measured EOAi on 30-day echocardiogram. PPMP was determined by 2 methods: 1) using normal EOA reference values previously reported for each valve model and size (PPMP1; n = 929 SAVR, 1,069 TAVR) indexed to BSA; and 2) using normal reference EOA predicted from aortic annulus size measured by computed tomography (PPMP2; n = 864 TAVR only) indexed to BSA. Primary endpoint was the composite of 5-year all-cause death and rehospitalization. Results The incidence of moderate and severe PPMP was much lower than PPMM in both SAVR (PPMP1: 28.4% and 1.2% vs. PPMM: 31.0% and 23.6%) and TAVR (PPMP1: 21.0% and 0.1% and PPMP2: 17.0% and 0% vs. PPMM: 27.9% and 5.7%). The incidence of severe PPMM and severe PPMP1 was lower in TAVR versus SAVR (P < 0.001). The presence of PPM by any method was associated with higher transprosthetic gradient. Severe PPMP1 was independently associated with events in SAVR after adjustment for sex and Society of Thoracic Surgeons score (hazard ratio: 3.18;95% CI: 1.69-5.96; P < 0.001), whereas no association was observed between PPM by any method and outcomes in TAVR. Conclusions EOAi measured by echocardiography results in a higher incidence of PPM following SAVR or TAVR than PPM based on predicted EOAi. Severe PPMP is rare (<1.5%), but is associated with increased all-cause death and rehospitalization after SAVR, whereas it is absent following TAVR

Left Ventricular Global Longitudinal Strain in Patients with Moderate Aortic Stenosis

BackgroundModerate aortic stenosis (AS) is associated with an increased risk for adverse events. Although reduced left ventricular (LV) global longitudinal strain (GLS) is associated with worse outcomes in patients with severe AS, its prognostic value in patients with moderate AS is unknown. The aim of this study was to investigate the prognostic implications of LV GLS in patients with moderate AS.MethodsLV GLS was evaluated using speckle-tracking echocardiography in patients with moderate AS (aortic valve area 1.0-1.5 cm2) and reported as absolute (i.e., positive) values. Patients were divided into three groups: LV ejection fraction (LVEF) ResultsA total of 760 patients (mean age, 71 ± 12 years; 61% men) were analyzed. During a median follow-up period of 50 months (interquartile range, 26-94 months), 257 patients (34%) died. Patients with LVEF P P = .592). LV GLS discriminated higher risk patients even among those with LVEF ≥ 60% (P P P P ConclusionsIn patients with moderate AS, reduced LV GLS is associated with an increased risk for all-cause mortality, even if LVEF is still preserved.</p

Acute Beneficial Hemodynamic Effects of a Novel 3D-Echocardiographic Optimization Protocol in Cardiac Resynchronization Therapy

Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming.25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization).EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001).Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT