One of the most common statistical analyses in experimental psychology concerns the comparison of two means using the frequentist t test. However, frequentist t tests do not quantify evidence and require various assumption tests. Recently, popularized Bayesian t tests do quantify evidence, but these were developed for scenarios where the two populations are assumed to have the same variance. As an alternative to both methods, we outline a comprehensive t test framework based on Bayesian model averaging. This new t test framework simultaneously takes into account models that assume equal and unequal variances, and models that use t-likelihoods to improve robustness to outliers. The resulting inference is based on a weighted average across the entire model ensemble, with higher weights assigned to models that predicted the observed data well. This new t test framework provides an integrated approach to assumption checks and inference by applying a series of pertinent models to the data simultaneously rather than sequentially. The integrated Bayesian model-averaged t tests achieve robustness without having to commit to a single model following a series of assumption checks. To facilitate practical applications, we provide user-friendly implementations in JASP and via the RoBTT package in R . A tutorial video is available at https://www.youtube.com/watch?v=EcuzGTIcorQ.
- Klíčová slova
- t-likelihood, t test, Bayes factor, Bayesian model-averaging, Robust inference, Unequal variances,
- MeSH
- Bayesova věta MeSH
- experimentální psychologie * metody MeSH
- interpretace statistických dat MeSH
- lidé MeSH
- statistické modely * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Gout and hyperuricemia increase cardiovascular disease risk, highlighting the need for improved risk stratification. In this pilot study, we evaluated the Coronary Event Risk Test (CERT) in 94 hyperuricemic and 196 gout patients, and 53 controls. Plasma ceramides were determined by liquid chromatography-mass spectrometry. Elevated CERT scores (≥7) occurred in 11.7 % (2-fold increase) of hyperuricemic and 31.12 % (5.5-fold increase) of gout patients compared to controls. Additionally, both hyperuricemic and gout patients with increased CERT also exhibited higher levels of inflammation and atherogenic index of plasma, both of which were significantly associated with CERT. Incorporating CERT into routine care may enhance risk stratification and guide targeted interventions in this patient population.
- Klíčová slova
- Cardiovascular risk, Ceramides, Coronary event risk test, Gout, Hyperuricemia, Lipidomics,
- MeSH
- biologické markery krev MeSH
- ceramidy * krev MeSH
- chromatografie kapalinová MeSH
- dna (nemoc) * krev diagnóza komplikace MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- hyperurikemie * krev diagnóza komplikace MeSH
- kardiovaskulární nemoci * diagnóza krev etiologie epidemiologie MeSH
- kyselina močová * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody pro podporu rozhodování * MeSH
- pilotní projekty MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- biologické markery MeSH
- ceramidy * MeSH
- kyselina močová * MeSH
of the original article, 'Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02'. Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate, which is a chemotherapy with a linker (deruxtecan) joined to an antibody (trastuzumab). Trastuzumab binds to the human epidermal growth factor receptor 2 (HER2) protein on cancer cells, where it releases the chemotherapy to kill these cells. The DESTINY-PanTumor02 clinical study tested the effectiveness of T-DXd for people with various HER2-expressing cancers and the safety of treatment. Previous results from DESTINY-PanTumor02 showed that T-DXd had antitumor activity, and the greatest effects were seen in people with the highest tumor level of HER2 [defined as immunohistochemistry (IHC) 3+]. In this previous analysis, the HER2 expression was measured at a central laboratory. In clinical practice, HER2 expression will likely be measured at a local laboratory, so understanding whether T-DXd has similar effects regardless of how HER2 expression is measured is important. Here, we looked at the effects of T-DXd based on the HER2 test result used to determine a person's eligibility for the study, which could be measured using a local or central laboratory. In people with IHC 3+ tumors (where HER2 was measured at a local or central laboratory), 51% had a decrease in the size or number of tumors, according to established criteria (referred to as an objective response), while, in people with IHC 2+ tumors, 26% had an objective response. Side effects with T-DXd were consistent with previous studies. These results confirm T-DXd has antitumor effects in HER2-expressing cancers where the HER2 expression is measured by a local or central laboratory.
- Klíčová slova
- Advanced/metastatic solid tumors, HER2 testing, HER2-expressing, Trastuzumab deruxtecan,
- MeSH
- imunohistochemie MeSH
- imunokonjugáty * terapeutické užití škodlivé účinky MeSH
- kamptothecin * analogy a deriváty terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- klinické zkoušky, fáze II jako téma MeSH
- lidé MeSH
- nádory * farmakoterapie metabolismus patologie MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- receptor erbB-2 * metabolismus MeSH
- sekundární analýza dat MeSH
- trastuzumab * terapeutické užití škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- ERBB2 protein, human MeSH Prohlížeč
- imunokonjugáty * MeSH
- kamptothecin * MeSH
- protinádorové látky imunologicky aktivní * MeSH
- receptor erbB-2 * MeSH
- trastuzumab deruxtecan MeSH Prohlížeč
- trastuzumab * MeSH
OBJECTIVES: Decision-analytic models assessing the value of emerging Alzheimer's disease (AD) treatments are challenged by limited evidence on short-term trial outcomes and uncertainty in extrapolating long-term patient-relevant outcomes. To improve understanding and foster transparency and credibility in modeling methods, we cross-compared AD decision models in a hypothetical context of disease-modifying treatment for mild cognitive impairment (MCI) due to AD. METHODS: A benchmark scenario (US setting) was used with target population MCI due to AD and a set of synthetically generated hypothetical trial efficacy estimates. Treatment costs were excluded. Model predictions (10-year horizon) were assessed and discussed during a 2-day workshop. RESULTS: Nine modeling groups provided model predictions. Implementation of treatment effectiveness varied across models based on trial efficacy outcome selection (clinical dementia rating - sum of boxes, clinical dementia rating - global, mini-mental state examination, functional activities questionnaire) and analysis method (observed severity transitions, change from baseline, progression hazard ratio, or calibration to these). Predicted mean time in MCI ranged from 2.6 to 5.2 years for control strategy and from 0.1 to 1.0 years for difference between intervention and control strategies. Predicted quality-adjusted life-year gains ranged from 0.0 to 0.6 and incremental costs (excluding treatment costs) from -US$66 897 to US$11 896. CONCLUSIONS: Trial data can be implemented in different ways across health-economic models leading to large variation in model predictions. We recommend (1) addressing the choice of outcome measure and treatment effectiveness assumptions in sensitivity analysis, (2) a standardized reporting table for model predictions, and (3) exploring the use of registries for future AD treatments measuring long-term disease progression to reduce uncertainty of extrapolating short-term trial results by health-economic models.
- Klíčová slova
- Alzheimer’s disease, cross-validation, decision-analytic modeling, health-economic evaluation,
- MeSH
- Alzheimerova nemoc * ekonomika farmakoterapie terapie MeSH
- analýza nákladů a výnosů * MeSH
- ekonomické modely MeSH
- kognitivní dysfunkce * ekonomika farmakoterapie MeSH
- kvalitativně upravené roky života MeSH
- lidé MeSH
- metody pro podporu rozhodování * MeSH
- progrese nemoci MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
IMPORTANCE: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance. OBJECTIVE: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD. DESIGN, SETTING, AND PARTICIPANTS: This was an international, multicenter, prospective, double-blind, placebo-controlled, randomized clinical trial including patients implanted with a de novo HM3 LVAD across 51 centers. Data analysis was conducted from April to July 2024. INTERVENTIONS: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg per day) or placebo, in addition to a vitamin K antagonist (VKA) targeted to an international normalized ratio of 2 to 3 in both groups. MAIN OUTCOMES AND MEASURES: Primary end point (assessed for noninferiority) was a composite of survival free of any nonsurgical (>14 days after implant) HRAEs including stroke, pump thrombosis, bleeding, and arterial peripheral thromboembolism at 12 months. Secondary end points included nonsurgical bleeding, stroke, and pump thrombosis events. RESULTS: Among 589 of 628 patients (mean [SD] age, 57.1 [13.7] years; 456 male [77.4%]) who contributed to the primary end point analysis, a history of PCI, CABG, stroke, or PVD was present in 41% (240 of 589 patients). There was no interaction between the presence of an atherosclerotic vascular condition and effect of aspirin compared with placebo (P for interaction= .23). The preset 10% noninferiority margin was not crossed for the studied subgroup of patients. Thrombotic events were rare, with no differences between aspirin and placebo in patients with and without vascular disease (P for interaction = .77). Aspirin treatment was associated with a higher rate of nonsurgical major bleeding events in the group with prior vascular condition history compared with those without aspirin (rate ratio for placebo compared with aspirin, 0.52; 95% CI, 0.35-0.79). CONCLUSIONS AND RELEVANCE: Results of this prespecified analysis of the ARIES-HM3 randomized clinical trial demonstrate that in patients with advanced heart failure who have classical indications for antiplatelet therapy use at the time of LVAD implantation, aspirin avoidance was safe and not associated with increased thrombosis risk. Importantly, elimination of aspirin was associated with no increased thrombosis but a reduction in nonsurgical bleeding events in patients with a history of PCI, CABG, stroke, or PVD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.
- MeSH
- Aspirin * aplikace a dávkování MeSH
- ateroskleróza * komplikace MeSH
- cévní mozková příhoda MeSH
- dvojitá slepá metoda MeSH
- fibrinolytika terapeutické užití MeSH
- inhibitory agregace trombocytů * terapeutické užití MeSH
- koronární angioplastika MeSH
- krvácení chemicky indukované MeSH
- lidé středního věku MeSH
- lidé MeSH
- podpůrné srdeční systémy * škodlivé účinky MeSH
- prospektivní studie MeSH
- sekundární analýza dat MeSH
- senioři MeSH
- srdeční selhání * terapie chirurgie komplikace MeSH
- trombóza prevence a kontrola MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- komentáře MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
- Názvy látek
- Aspirin * MeSH
- fibrinolytika MeSH
- inhibitory agregace trombocytů * MeSH
BACKGROUND: Observational data on composite scores often comes with missing component information. When a complete-case (CC) analysis of composite scores is unbiased, preferable approaches of dealing with missing component information should also be unbiased and provide a more precise estimate. We assessed the performance of several methods compared to CC analysis in estimating the means of common composite scores used in axial spondyloarthritis research. METHODS: Individual mean imputation (IMI), the modified formula method (MF), overall mean imputation (OMI), and multiple imputation of missing component values (MI) were assessed either analytically or by means of simulations from available data collected across Europe. Their performance in estimating the means of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Bath Ankylosing Spondylitis Functional Index (BASFI), and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) in cases where component information was set missing completely at random was compared to the CC approach based on bias, variance, and coverage. RESULTS: Like the MF method, IMI uses a modified formula for observations with missing components resulting in modified composite scores. In the case of an unbiased CC approach, these two methods yielded representative samples of the distribution arising from a mixture of the original and modified composite scores, which, however, could not be considered the same as the distribution of the original score. The IMI and MF method are, thus, intrinsically biased. OMI provided an unbiased mean but displayed a complex dependence structure among observations that, if not accounted for, resulted in severe coverage issues. MI improved precision compared to CC and gave unbiased means and proper coverage as long as the extent of missingness was not too large. CONCLUSIONS: MI of missing component values was the only method found successful in retaining CC's unbiasedness and in providing increased precision for estimating the means of BASDAI, BASFI, and ASDAS-CRP. However, since MI is susceptible to incorrect implementation and its performance may become questionable with increasing missingness, we consider the implementation of an error-free CC approach a valid and valuable option. TRIAL REGISTRATION: Not applicable as study uses data from patient registries.
- Klíčová slova
- Axial spondyloarthritis, Complete-case analysis, Composite score, Missing components, Multiple imputation,
- MeSH
- axiální spondyloartritida * diagnóza MeSH
- C-reaktivní protein analýza MeSH
- interpretace statistických dat MeSH
- lidé MeSH
- stupeň závažnosti nemoci MeSH
- výzkumný projekt MeSH
- zkreslení výsledků (epidemiologie) MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Evropa MeSH
- Názvy látek
- C-reaktivní protein MeSH
Laboratory measurements used for safety assessments in clinical trials are subject to the limits of the used laboratory equipment. These limits determine the range of values which the equipment can accurately measure. When observations fall outside the measurable range, this creates a problem in estimating parameters of the normal distribution. It may be tempting to use methods of estimation that are easy to implement, however selecting an incorrect method may lead to biased estimates (under- or overestimation) and change the research outcomes, for example, incorrect result of two-sample test about means when comparing two populations or biased estimation of regression line. In this article, we consider the use of four methods: ignoring unmeasured observations, replacing unmeasured observations with a multiple of the limit, using a truncated normal distribution, and using a normal distribution with censored observations. To compare these methods we designed a simulation study and measured their accuracy in several different situations using relative error μ ̂ - μ μ $$ \frac{\hat{\mu}-\mu }{\mu } $$ , ratio σ ̂ σ $$ \frac{\hat{\sigma}}{\sigma } $$ , and mean square errors of both parameters. Based on the results of this simulation study, if the amount of observations outside of measurable range is below 40%, we recommend using a normal distribution with censored observations in practice. These recommendations should be incorporated into guidelines for good statistical practice. If the amount of observations outside of measurable range exceeds 40%, we advise not to use the data for any statistical analysis. To illustrate how the choice of method can affect the estimates, we applied the methods to real-life laboratory data.
- Klíčová slova
- clinical trial, estimation techniques, limit of detection, limit of quantitation, measurable range, simulation study,
- MeSH
- interpretace statistických dat MeSH
- klinické zkoušky jako téma metody MeSH
- lidé MeSH
- normální rozdělení MeSH
- počítačová simulace * MeSH
- statistické modely MeSH
- výzkumný projekt MeSH
- zkreslení výsledků (epidemiologie) MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Feature-based molecular networking (FBMN) is a popular analysis approach for liquid chromatography-tandem mass spectrometry-based non-targeted metabolomics data. While processing liquid chromatography-tandem mass spectrometry data through FBMN is fairly streamlined, downstream data handling and statistical interrogation are often a key bottleneck. Especially users new to statistical analysis struggle to effectively handle and analyze complex data matrices. Here we provide a comprehensive guide for the statistical analysis of FBMN results, focusing on the downstream analysis of the FBMN output table. We explain the data structure and principles of data cleanup and normalization, as well as uni- and multivariate statistical analysis of FBMN results. We provide explanations and code in two scripting languages (R and Python) as well as the QIIME2 framework for all protocol steps, from data clean-up to statistical analysis. All code is shared in the form of Jupyter Notebooks ( https://github.com/Functional-Metabolomics-Lab/FBMN-STATS ). Additionally, the protocol is accompanied by a web application with a graphical user interface ( https://fbmn-statsguide.gnps2.org/ ) to lower the barrier of entry for new users and for educational purposes. Finally, we also show users how to integrate their statistical results into the molecular network using the Cytoscape visualization tool. Throughout the protocol, we use a previously published environmental metabolomics dataset for demonstration purposes. Together, the protocol, code and web application provide a complete guide and toolbox for FBMN data integration, cleanup and advanced statistical analysis, enabling new users to uncover molecular insights from their non-targeted metabolomics data. Our protocol is tailored for the seamless analysis of FBMN results from Global Natural Products Social Molecular Networking and can be easily adapted to other mass spectrometry feature detection, annotation and networking tools.
AIMS: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals. METHODS AND RESULTS: The updated LIFE-CVD (i.e. LIFE-CVD2) models were derived using individual participant data from 44 cohorts in 13 countries (687 135 individuals without established CVD, 30 939 CVD events in median 10.7 years of follow-up). LIFE-CVD2 uses sex-specific functions to estimate the lifetime risk of fatal and non-fatal CVD events with adjustment for the competing risk of non-CVD death and is systematically recalibrated to four distinct European risk regions. The updated models showed good discrimination in external validation among 1 657 707 individuals (61 311 CVD events) from eight additional European cohorts in seven countries, with a pooled C-index of 0.795 (95% confidence interval 0.767-0.822). Predicted and observed CVD event risks were well calibrated in population-wide electronic health records data in the UK (Clinical Practice Research Datalink) and the Netherlands (Extramural LUMC Academic Network). When using LIFE-CVD2 to estimate potential gain in CVD-free life expectancy from preventive therapy, projections varied by risk region reflecting important regional differences in absolute lifetime risk. For example, a 50-year-old smoking woman with a systolic blood pressure (SBP) of 140 mmHg was estimated to gain 0.9 years in the low-risk region vs. 1.6 years in the very high-risk region from lifelong 10 mmHg SBP reduction. The benefit of smoking cessation for this individual ranged from 3.6 years in the low-risk region to 4.8 years in the very high-risk region. CONCLUSION: By taking into account geographical differences in CVD incidence using contemporary representative data sources, the recalibrated LIFE-CVD2 model provides a more accurate tool for the prediction of lifetime risk and CVD-free life expectancy for individuals without previous CVD, facilitating shared decision-making for cardiovascular prevention as recommended by 2021 European guidelines.
The study introduces LIFE-CVD2, a new tool that helps predict the risk of heart disease over a person’s lifetime, and highlights how where you live in Europe can affect this risk.Using health information from over 687 000 people, LIFE-CVD2 looks at things like blood pressure and whether someone smokes to figure out their chance of having heart problems later in life. Health information from another 1.6 million people in seven different European countries was used to show that it did a good job of predicting who might develop heart disease.Knowing your heart disease risk over your whole life helps doctors give you the best advice to keep your heart healthy. Let us say there is a 50-year-old woman who smokes and has a bit high blood pressure. Right now, she might not look like she is in danger. But with the LIFE-CVD2 tool, doctors can show her how making changes today, like lowering her blood pressure or stopping smoking, could mean many more years without heart problems. These healthy changes can make a big difference over many years.
- Klíčová slova
- Cardiovascular disease, Lifetime, Prevention, Primary prevention, Risk prediction,
- MeSH
- časové faktory MeSH
- dospělí MeSH
- hodnocení rizik MeSH
- kardiovaskulární nemoci * prevence a kontrola epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody pro podporu rozhodování MeSH
- prognóza MeSH
- rizikové faktory kardiovaskulárních chorob * MeSH
- rizikové faktory MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
AIMS: While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients' stratification. The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended Global Registry of Acute Coronary Events (GRACE) score. METHODS AND RESULTS: A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. Data from 1135 patients (aged 64 ± 12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire and clinical variables were used as possible predictors. The best model included the following variables: age, HF history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months [the area under the receiver operating curve (AUC) 90.1, 95% confidence interval (CI) 81.8-98.4 vs. 77.4, 95% CI 62.2-92.5, P = 0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5-96.0 vs. 76.2, 95% CI 64.7-87.7, P = 0.004). CONCLUSION: The PragueMi score combining HF symptoms and clinical variables performs better than the currently recommended GRACE score.
The prognosis of patients after myocardial infarction is heterogeneous. Thus, risk stratification is needed to identify and intervene patients at increased risk. While heart failure (HF) symptoms are associated with adverse prognosis, they are not used for patients’ stratification. We have developed and internally validated the PragueMi score, which integrates clinical risk factors at the time of hospitalization and HF symptoms determined remotely by a questionnaire 1 month after hospital discharge. PragueMi score was able to better stratify patients’ risk as compared with the currently recommended Global Registry of Acute Coronary Events score.
- Klíčová slova
- Heart failure, Mortality, Myocardial infarction, Questionnaire, Risk prediction, Symptoms,
- MeSH
- časové faktory MeSH
- hodnocení rizik MeSH
- infarkt myokardu * mortalita diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody pro podporu rozhodování MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- prospektivní studie MeSH
- reprodukovatelnost výsledků MeSH
- rizikové faktory MeSH
- senioři MeSH
- srdeční selhání * mortalita diagnóza patofyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- validační studie MeSH