Using multicentre RCT-based individual patient level data to populate decision analytic cost-effectiveness models for location-specific decision making

Objectives: To develop methodology for the analysis of individual patient level data from multicentre/multinational randomized controlled trials with the aim of estimating location-specific parameters to populate decision models for location-specific decision making. Methods: Multilevel or hierarchical modelling is the analytical framework used to handle hierarchical cost-effectiveness data. Hierarchical modelling was developed in a Bayesian framework and Bayesian shrinkage estimation procedures were used to obtain location-specific cost-effectiveness estimates. Results: Using data from a recently conducted economic analysis of the RITA 3 trial, locationspecific cost-effectiveness measures were obtained and compared to the trial-wide results. For the analysed centres, the centre-specific cost-effectiveness planes showed higher variability in mean differential cost and mean differential QALY estimates compared to the trial wide results, with the latter having longer left tail estimate distribution. The majority of the location-specific incremental cost-effectiveness ratio results show higher cost per QALY for the intervention strategy compared to the trial wide results (approx. £41,400/QALY). With respect to centre-specific cost-effectiveness acceptability curves, the curves for the selected centres display great variability across centres in cost-effectiveness for given values of the threshold, λ. If the decision maker is willing to pay £50,000 for an additional QALY, the probability that the intervention strategy is cost-effective is, for instance, 0.34 for centre 37, compared to the 0.65 for the trial wide results. Conclusions: This thesis shows how Bayesian hierarchical modelling can be used to estimate more appropriate cluster-specific parameters for use in decision analytic models where individual patient level data from a multi-location trial are available. Bayesian hierarchical modelling estimates can be used to explore correctly the variability between centres/countries of the cost-effectiveness results allowing the correct quantification of uncertainty by adjusting the standard errors to reflect the estimates variability both within and between locations

Composição e improvisação: escrita vs "não escrita"

O objectivo do trabalho que se apresenta, que corresponde a um projecto realizado para obtenção do grau de Mestre em Composição e Teoria Musical, foi explorar a relação entre a Composição e a Improvisação com base numa reflexão teórica acerca de questões relevantes, como o problema de combinar partes escritas, notadas tradicionalmente, com partes mais abertas, que quase dispensam a escrita e em que se faz uso da improvisação. Nele se aborda o problema de encontrar processos geradores de ideias musicais que não passam necessariamente pela notação tradicional, combinando a escrita e improvisação mais idiomática do jazz com conceitos como indeterminação e abertura, e que tornam possível a composição de peças musicais em tempo real. Na segunda parte deste trabalho, é apresentada a descrição e análise dos processos utilizados na escrita de música para um grande ensemble de Jazz, um dos objectivos da Tese de Mestrado, assim como os processos usados na improvisação e uma análise dos resultados obtidos numa performance realizada no final do projecto, dirigida com base na linguagem do Soundpainting.The objective of the work presented, which corresponds to a project undertaken for the degree of Master of Composition and Music Theory, was to explore the relationship between composition and improvisation based on a theoretical reflection on relevant issues, as the problem of combining traditionally notated written pieces with more open pieces that nearly dispense writing and make use of improvisation. The work presented addresses the issue of finding processes that generate musical ideas which do not necessarily involve the use of traditional notation, combining the more idiomatic writing and improvisation of jazz with concepts such as indeterminacy and openness, that make possible the composition of musical pieces in real time. In the second part of this work, the description and analysis of the processes used in writing music for a large ensemble Jazz, one of the objectives of the Master Thesis, is presented, as well as the processes used in improvisation and an analysis of the results obtained in a performance held at the end of the project, directed using the Soundpainting language

Treino auditivo como instrumento para a improvisação - reconhecimento de progressões harmónicas

O presente relatório de estágio está baseado na minha prática educativa integrada na variante jazz do curso secundário de música do Conservatório de Música do Porto. Essa prática não se foca apenas no tipo de aula individual, mas também em aulas de combo e treino auditivo. O relatório de Estágio pretende ser uma reflexão acerca do ensino do jazz com o objectivo de melhorar os métodos de ensino deste estilo musical. O projecto de investigação foca-se na questão da importância do treino auditivo como ferramenta para a improvisação. Na minha prática como docente de instrumento, combo e treino auditivo tenho assistido muitas vezes a uma “desvalorização” do treino auditivo por parte dos alunos. Este deve acompanhar o estudo do instrumento e não deve ser visto como algo separado deste. A importância de reconhecer e reproduzir intervalos, chordscales, reconhecer acordes, progressões harmónicas, forma bem como ser capaz de improvisar utilizando apenas a voz no sentido de se conseguir cantar o que se ouve interiormente mostra-se como uma ferramenta essencial para se ser um músico de jazz.The present report is based on my educational practice integrated in the jazz variant of the secondary course of music of the Conservatory of Music of Porto. This practice focuses not only on the individual class type but also on combo lessons and ear training. The report aims to be a reflection on the teaching of jazz with the aim of improving the teaching methods of this musical style. The research project focuses on the question of the importance of auditory training as a tool for improvisation. In my practice as an instrument teacher, combo and ear training I have often witnessed a "devaluation" of the ear training by the students. This should accompany the study of the instrument and should not be seen as something separate from this. The importance of recognizing and reproducing intervals, chordscales, recognizing chords, harmonic progressions, as well as being able to improvise using only the voice in the sense of being able to sing what we gear, is an essential tool for be a jazz musician

Experimental Validation of a Double-Deck Track-Bridge System under Railway Traffic

This article describes the experimental and numerical evaluation of the dynamic behaviour of the Cascalheira bridge, located on the Northern Line of the Portuguese railway network. The bridge has a short span formed by two filler-beam half-decks, each one accommodating a railway track. The study includes the development of a finite element numerical model in ANSYS® software, as well as in situ dynamic characterization tests of the structure, namely ambient vibration tests, for the estimation of natural frequencies, modes shapes and damping coefficients, and a dynamic test under railway traffic, particularly for the passage of the Alfa Pendular train. The damping coefficients’ estimation was performed based on the Prony method, which proved effective in situations where the classical methods (e.g., decrement logarithm) tend to fail, particularly in the case of mode shapes with closed natural frequencies, as typically happens with the first vertical bending and torsion modes. The updating of the numerical model of the bridge was carried out using an iterative methodology based on a genetic algorithm, allowing an upgrade of the agreement between the numerical and experimental modal parameters. Particular attention was given to the characterization of the ballast degradation over the longitudinal joint between the two half-decks, given its influence in the global dynamic behavior of this type of double-deck bridges. Finally, the validation of the numerical model was performed by comparing the acceleration response of the structure under traffic actions, by means of numerical dynamic analyses considering vehicle-bridge interaction and including track irregularities, with the ones obtained by the dynamic test under traffic actions. The results of the calibrated numerical model showed a better agreement with the experimental results based on the accelerations evaluated in several measurement points located in both half-decks. In the validation process the vertical stiffness of the supports, as well as the degradation of the ballast located over the longitudinal joint between half-decks, was demonstrated to be relevant for the accuracy and effectiveness of the numerical models.This work has been supported by the projects IN2TRACK2 and IN2TRACK3 funded by the Shift2Rail Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme under grant agreements No. 826255 and No. 101012456, respectively. Moreover, this work was also financially supported by Base Funding—UIDB/04708/2020 and Programmatic Funding— UIDP/04708/2020 of the CONSTRUCT—Instituto de I&D em Estruturas e Construções—funded by national funds through the FCT/MCTES (PIDDAC). Finally, the second and fourth authors acknowledge Grant No. 2020.00305.CEECIND from the Stimulus of Scientific Employment, Individual Support (CEECIND)—3rd Edition provided by “FCT—Fundação para a Ciência e Tecnologia” and project operation NORTE-08-5369-FSE-000027 by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Social Fund (ESF), respectively.info:eu-repo/semantics/publishedVersio

High-throughput non-invasive prenatal testing for fetal rhesus D status in RhD-negative women not known to be sensitised to the RhD antigen : a systematic review and economic evaluation

Background: High-throughput non-invasive prenatal testing (NIPT) for fetal rhesus (D antigen) (RhD) status could avoid unnecessary treatment with routine anti-D immunoglobulin for RhD-negative women carrying a RhD-negative fetus, although this may lead to an increased risk of RhD sensitisations. Objectives: To systematically review the evidence on the diagnostic accuracy, clinical effectiveness and implementation of high-throughput NIPT and to develop a cost-effectiveness model. Methods: We searched MEDLINE and other databases, from inception to February 2016, for studies of high-throughput NIPT free-cell fetal deoxyribonucleic acid (DNA) tests of maternal plasma to determine fetal RhD status in RhD-negative pregnant women who were not known to be sensitised to the RhD antigen. Study quality was assessed with the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) and A Cochrane Risk of Bias Assessment Tool: for Non-Randomised Studies of Interventions (ACROBAT-NRSI). Summary estimates of false-positive rates (FPRs) and false-negative rates (FNRs) were calculated using bivariate models. Clinical effectiveness evidence was used to conduct a simulation study. We developed a de novo probabilistic decision tree-based cohort model that considered four alternative ways in which the results of NIPT could guide the use of anti-D immunoglobulin antenatally and post partum. Sensitivity analyses (SAs) were conducted to address key uncertainties and model assumptions. Results: Eight studies were included in the diagnostic accuracy review, seven studies were included in the clinical effectiveness review and 12 studies were included in the review of implementation. Meta-analyses included women mostly at or post 11 weeks’ gestation. The pooled FNR (women at risk of sensitisation) was 0.34% [95% confidence interval (CI) 0.15% to 0.76%] and the pooled FPR (women needlessly receiving anti-D) was 3.86% (95% CI 2.54% to 5.82%). SAs did not materially alter the overall results. Data on clinical outcomes, including sensitisation rates, were limited. Our simulation suggests that NIPT could substantially reduce unnecessary use of antenatal anti-D with only a small increase in the risk of sensitisation. All large implementation studies suggested that large-scale implementation of high-throughput NIPT was feasible. Seven cost-effectiveness studies were included in the review, which found that the potential for the use of NIPT to produce cost savings was dependent on the cost of the test. Our de novo model suggested that high-throughput NIPT is likely to be cost saving compared with the current practice of providing routine antenatal anti-D prophylaxis to all women who are RhD negative. The extent of the cost saving appeared to be sufficient to outweigh the small increase in sensitisations. However, the magnitude of the cost saving is highly sensitive to the cost of NIPT itself. Limitations: There was very limited evidence relating to the clinical effectiveness of high-throughput NIPT, with no evidence on potential adverse effects. The generalisability of the findings to non-white women and multiple pregnancies is unclear. Conclusions: High-throughput NIPT is sufficiently accurate to detect fetal RhD status in RhD-negative women from 11 weeks’ gestation and would considerably reduce unnecessary treatment with routine anti-D immunoglobulin, potentially resulting in cost savings of between £485,000 and £671,000 per 100,000 pregnancies if the cost of implementing NIPT is in line with that reflected in this evaluation

Early season symptoms of stem, inflorescences and flowers of grapevine associated with Botryosphaeriaceae species

Botryosphaeria dieback caused by several Botryosphaeriaceae species is one of the most important grapevine trunk diseases a ecting vineyards worldwide. These fungi cause wedge-shaped perennial cankers and black streaking of the wood and have also been associated with intervein leaf chlorosis, dried or mummified berries, and eventually, the death of the plant. Early season symptoms may sometimes be disregarded by growers, being mistaken with symptoms from other diseases such as downy mildew or botrytis rot. Currently, few studies are available to determine what species may be causing these early season symptoms in grapevines. During the 2018 season, during the flowering period, grapevine samples showing necrosis on green shoots, dried inflorescences, and flowers, were collected in vineyards throughout the central regions of Portugal. Isolations were performed from symptomatic organs, and twenty-three isolates of Botryosphaeriaceae were selected. An analysis of the ITS and part of the translation elongation factor 1- sequences was performed, revealing that the two main species apparently responsible for these symptoms were Diplodia seriata and Neofusicoccum parvum. In pathogenicity tests conducted on 1-year-old plants grown under controlled conditions in a greenhouse and on field-grown clusters, symptoms were reproduced, confirming the pathogenic behavior of the selection of isolatesinfo:eu-repo/semantics/publishedVersio

Bayesian econometric modelling of observational data for cost-effectiveness analysis : establishing the value of Negative Pressure Wound Therapy in the healing of open surgical wounds

Background/Introduction In the absence of evidence from randomised controlled trials on the relative effectiveness of treatments, cost-effectiveness analyses increasingly use observational data instead. Treatment assignment is not, however, randomised, and naïve estimates of treatment effect may be biased. To deal with this bias, one may need to adjust for observed and unobserved confounders. In this work we aim to explore and discuss the challenges of these adjustment strategies using a case study of negative pressure wound therapy (NPWT) versus standard dressings for the treatment of open surgical wounds. Methods Time to wound healing, was estimated using Bayesian inference methods: i) OLS models, ii) OLS model adjusting for potential observed confounders and iii) two-stage instrumental variable (IV) models. A panel data regression approach was used to model health-related quality of life weights and costs. Cost-effectiveness estimates were obtained for selected models. Results The case study was a longitudinal cohort study of 393 participants followed up by on average 500 days. In all the modelling approaches we implemented, the treatment NPWT was estimated to offer less benefit at higher costs than competing interventions. Conclusions This study shows how to use observational data to assess cost-effectiveness by adjusting for both observable and unobservable confounders. Within the case study, we could not demonstrate that existing uncontrolled confounding affects the effectiveness of NPWT. There was no evidence that NPWT was effective or cost-effective compared to standard dressings for the treatment of SWHSI

Methods for network meta-analysis of continuous outcomes using individual patient data : a case study in acupuncture for chronic pain

Background: Network meta-analysis methods, which are an extension of the standard pair-wise synthesis framework, allow for the simultaneous comparison of multiple interventions and consideration of the entire body of evidence in a single statistical model. There are well-established advantages to using individual patient data to perform network meta-analysis and methods for network meta-analysis of individual patient data have already been developed for dichotomous and time-to-event data. This paper describes appropriate methods for the network meta-analysis of individual patient data on continuous outcomes. Methods: This paper introduces and describes network meta-analysis of individual patient data models for continuous outcomes using the analysis of covariance framework. Comparisons are made between this approach and change score and final score only approaches, which are frequently used and have been proposed in the methodological literature. A motivating example on the effectiveness of acupuncture for chronic pain is used to demonstrate the methods. Individual patient data on 28 randomised controlled trials were synthesised. Consistency of endpoints across the evidence base was obtained through standardisation and mapping exercises. Results: Individual patient data availability avoided the use of non-baseline-adjusted models, allowing instead for analysis of covariance models to be applied and thus improving the precision of treatment effect estimates while adjusting for baseline imbalance. Conclusions: The network meta-analysis of individual patient data using the analysis of covariance approach is advocated to be the most appropriate modelling approach for network meta-analysis of continuous outcomes, particularly in the presence of baseline imbalance. Further methods developments are required to address the challenge of analysing aggregate level data in the presence of baseline imbalance

Immediate Versus Triggered Transfusion for Children with Uncomplicated Severe Anaemia

Background: The World Health Organization recommends a haemoglobin transfusion threshold of 0.2) nor evidence of differences between groups in re-admissions (p=0.36), serious adverse events (p=0.36) nor in haemoglobin recovery at 180-days (p=0.08). Length-of-stay was mean 0.9 days longer in the triggered group. Conclusions: There was no evidence of differences in clinical outcomes over 6 months with triggered vs immediate transfusion. Triggered transfusion reduced blood-volume requirements by 60% but increased length-of-stay by 20% and required repeated haemoglobin monitoring and surveillance