1,720,979 research outputs found
Patient-Reported Outcomes in cardiovascular trials for the treatment of Heart Failure: alternative approaches for quantitative synthesis and joint evaluation with survival.
Full text linkI Patient-Reported Outcomes (PRO) sono ormai cruciali nella ricerca clinica per valutare sintomi e qualità della vita (QoL) dal punto di vista dei pazienti. Nello scompenso cardiaco (HF) il Kansas City Cardiomyopathy Questionnaire (KCCQ) è lo strumento di riferimento per la sua sensibilità e specificità. Tuttavia, l’uso dei PRO comporta nuove sfide metodologiche: le differenze nei formati dei questionari, nelle scale di punteggio e negli intervalli di follow-up rendono difficile il confronto tra studi e la sintesi dei dati. Inoltre, l’interazione tra QoL e sopravvivenza presenta ulteriori complessità. Poiché i PRO sono raccolti solo nei pazienti in vita, la mortalità precoce di coloro con QoL più bassa può portare a una sovrastima della QoL, distorcendo la percezione degli effetti del trattamento. Infine, i modelli di sopravvivenza basati solo sui valori iniziali dei PRO rischiano di trascurare cambiamenti importanti nella QoL correlati alla prognosi.
L’obiettivo di questa tesi era affrontare le complessità introdotte dai PRO nelle metanalisi e negli studi clinici.
Il primo obiettivo era sviluppare una metodologia meta-analitica per confrontare i PRO tra gruppi di trattamento in momenti predefiniti riducendo la perdita di informazioni. Questa è stata applicata ai dati di trial randomizzati (RCT) che confrontavano gli inibitori SGLT2 (SGLT2i) con lo standard di cura (SOC) in pazienti con HF. La misura di interesse era la differenza nel cambiamento medio del punteggio complessivo KCCQ tra i gruppi SGLT2i e SOC a 3 e 6 mesi dal basale. Sono stati applicati due metodi: un approccio tradizionale su dati aggregati, migliorato per gestire i dati mancanti, e un approccio basato sui dati pseudo-individuali ricostruiti (pseudo-IPD). Questo ha utilizzato due approcci meta-analitici distinti: a due stadi, ottenendo le stime specifiche per ciascun studio dagli pseudo-IPD separatamente e poi combinandole in un modello tradizionale; e a uno stadio, basato su un modello lineare a effetti misti (LMM), che ha fornito stime pooled delle differenze di trattamento ai vari momenti predefiniti, esplorando anche le interazioni tra tempo e trattamento. I risultati hanno dimostrato che l’uso degli pseudo-IPD e del LMM migliorano la precisione delle stime, consentendo una visione più completa degli effetti del trattamento nel tempo. L'uso di metodi per minimizzare la perdita di informazioni, come l'estrazione grafica o l'interpolazione lineare, è stato essenziale per ottenere risultati standardizzati tra studi con diversi intervalli di follow-up. Tali affinamenti possono aiutare i medici a comprendere meglio sia l'entità dei miglioramenti nella QoL sia i tempi in cui si verificano.
Il secondo obiettivo era valutare modelli statistici per analizzare congiuntamente sopravvivenza e QoL, affrontando le sfide del trial MITRADVANCE-HF, un RCT che valuta l’efficacia della riparazione percutanea della valvola mitrale in pazienti con HF avanzato. In questo contesto, sono stati recentemente proposti modelli congiunti che collegano un LMM per misure ripetute a un modello di sopravvivenza per i dati di tempo dell’evento. Poichè il trial MITRADVANCE-HF è ancora in corso, sono stati utilizzati dati simulati di sopravvivenza e QoL per esplorare vari scenari. Per valutare la robustezza e le proprietà dei modelli congiunti, sono stati confrontati con metodi tradizionali, come il modello di Cox con covariate tempo-dipendenti. Il modello congiunto ha dimostrato maggiore accuratezza nella stima degli effetti del trattamento e nel rilevare l’effetto protettivo della QoL sulla sopravvivenza, mentre i modelli più semplici hanno mostrato rilevanti bias.
Nel complesso, i risultati evidenziano il valore di integrare tecniche avanzate per l’analisi dei PRO in vari tipi di studio. Tali metodi rafforzano le conclusioni basate sull'evidenza e promuovono una comprensione più completa degli effetti dei trattamenti sulla QoL e sulla sopravvivenza.Patient-Reported Outcomes (PROs) have become essential in clinical research, as they directly capture patients’ perspectives on symptoms and quality of life (QoL). In heart failure (HF), the Kansas City Cardiomyopathy Questionnaire (KCCQ) has emerged as a preferred tool for assessing QoL due to its sensitivity and specificity. However, PROs present new methodological challenges: differences in questionnaire formats, scoring scales, and follow-up intervals make it difficult to align data across studies, complicating comparisons and data synthesis. Additionally, the interplay between QoL and survival presents unique complexities. PROs are collected only from alive patients, so early mortality among those with lower QoL can lead to an overestimation of QoL, distorting perceived treatment effects. Additionally, survival models based only on baseline PROs may miss important QoL changes that correlate with prognosis.
The overall aim of this thesis was to address the complexities introduced by PROs in meta-analyses and survival analysis of clinical studies.
The first objective was to propose a meta-analytic methodology capable of comparing continuous PROs between treatment groups at specified timepoints while minimizing information loss. This approach was applied to PRO data from randomized controlled trials (RCTs) comparing SGLT2 inhibitors (SGLT2i) with standard of care (SOC) in patients with HF. The effect size of interest was the difference in mean change of the KCCQ overall score (KCCQ-OSS) between SGLT2i and SOC groups at 3 and 6 months from baseline. Two complementary methods were used: a traditional aggregated data (AD) approach with specific enhancements for handling missing data and an approach based on reconstructed pseudo individual patient data (IPD). The synthesis was conducted using two meta-analytical approaches: a two-stage approach, where study-specific estimates were first obtained from pseudo-IPD for each study and then combined by a traditional model; and a one-stage approach using a linear mixed-effects model (LMM), which provided pooled estimates of treatment differences at predefined timepoints and explored interactions between time and treatment effects. Results showed that pseudo-IPD reconstruction and the LMM improved accuracy and precision of pooled estimates, allowing a clearer understanding of treatment effects over time. Methods to minimize information loss, including graphical extraction or linear interpolation, were essential for achieving standardized results across studies with varying follow-up intervals. These refinements could help healthcare providers gain clearer insights into the timing and magnitude of QoL improvements.
The second objective was to evaluate statistical models for analyzing survival and QoL outcomes, addressing specific challenges posed by the MITRADVANCE-HF trial, an RCT assessing percutaneous mitral valve repair in patients with advanced HF. Joint models were proposed to capture the dependency structure between longitudinal predictors and survival outcome, linking a LMM for repeated measures with a survival model for event-time data. Since MITRADVANCE-HF is still ongoing, simulated survival and QoL data were used to explore possible scenarios. To assess the robustness of joint models for analyzing these data, they were compared with traditional methods like the Cox model with time-dependent covariates. The joint model demonstrated superior accuracy in estimating treatment effects and capturing the protective influence of QoL on survival, whereas simpler models exhibited substantial bias.
Together, the findings highlight the value of integrating advanced analytical techniques for PRO data across different study designs. These methods not only strengthen evidence-based conclusions but also promote a more comprehensive understanding of treatment impacts on both QoL and survival, supporting a more holistic approach to patient care
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Surrogate endpoints for overall survival in randomized clinical trials testing immune checkpoint inhibitors: a systematic review and meta-analysis
No full textIntroduction: There is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs). Methods: We systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients. We performed a meta-analysis of RCTs to compare the surrogacy value of PFS and modified-PFS (mPFS) for OS in RCTs testing ICIs, when the treatment effect is measured by the hazard ratio (HR) for OS, and by the HR and the ratio of restricted mean survival time (rRMST) for PFS and mPFS. Results: 61 RCTs (67 treatment comparisons and 36,034 patients) were included in the analysis. In comparisons testing ICI plus chemotherapy, HRPFS and HRmPFS both had a strong surrogacy value (R-2 = 0.74 and R-2 = 0.81, respectively). In comparisons testing ICI as monotherapy, HRPFS was the best surrogate, although having a moderate correlation (R-2 = 0.58). In comparisons testing ICI plus other treatment(s), the associations were very weak for all the surrogate endpoints and treatment effect measures, with R-2 ranging from 0.01 to 0.22. Conclusion: In RCTs testing ICIs, the value of potential surrogates for HROS was strongly affected by the type of treatment(s) tested. The evidence available supports HRPFS as the best surrogate, and disproves the use of alternative endpoints, such as the mPFS, or treatment effect measures, such as the RMST
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Biologics as well as inhaled anti-asthmatic therapy achieve clinical remission: Evidence from the Severe Asthma Network in Italy (SANI)
No full textBackground: This study aimed to evaluate the impact of severe asthma (SA) treatments after 12 months in achieving clinical remission (CR) within the context of the Severe Asthma Network in Italy (SANI) using the recent SANI definition of CR on treatment. Methods: CR has been defined by SANI as complete, partial, and no CR. Complete CR is defined by the absence of oral corticosteroids (OCS), no symptoms, no exacerbations, and stable lung function, and partial CR requires the absence of OCS and the fulfillment of 2 out of the other 3 criteria. Patients who do not meet the previous criteria do not reach CR. Results: After 12 months of treatment, 283 patients were selected to evaluate the effectiveness of biologics (225 patients) and inhaled therapy (58 patients) in achieving CR. Among patients treated with biologic agents, 45.8% reached complete CR, 23.1% partial CR, and 31.1% no CR. Differences in CR achievement according to type of biologic agent administered were observed. Interesting results were found when assessing the inhaled therapy (ICS/LABA/LAMA and no biologics) effectiveness: 34.5% patients reached complete CR, 34.5% partial CR, and 31.0% did not reach CR. This finding is noteworthy since it further supports the efficacy of inhaled treatment in certain SA patients and highlights the relevance of using CR as a modern outcome of SA treatments. Chronic rhinosinusitis with nasal polyps (CRSwNP) comorbidity was associated, though not significantly, with CR achievement in patients treated with biologics. Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores significantly impacted CR (p = 0.003 and p = 0.027, respectively), while biomarkers, namely IgE, blood eosinophils, or fractional exhaled nitric oxide (FeNO), were not associated with CR achievement. Conclusions: This study confirmed the effectiveness of biologics in reaching CR and demonstrated also inhaled therapies able to achieve CR. These innovative findings should encourage post hoc analysis of randomized clinical trials or even retrospective analysis of SA patient cohorts to evaluate CR with different inhaled treatments and further define the populations eligible for each treatment. Trial registration: ClinicalTrials.gov ID: NCT06625216; Central Ethics Committee: Comitato Etico Area Vasta Nord-Ovest Toscana (study number 1245/2016, protocol number:73714)
- …
