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1.
J Antimicrob Chemother ; 76(12 Suppl 2): ii2-ii6, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312651

RESUMO

OBJECTIVES: This article introduces a series of articles on antibiotic consumption in the community between 1997 and 2017, which provide an update of previous articles covering the periods 1997-2003 and 1997-2009. METHODS: In this article, differences in participating countries, the ATC/DDD classification system, and data collection, validation and analysis between the current and previous series are described. RESULTS: In the previous series, 33 European countries provided valid data for further analysis, while the current series focused on 30 countries belonging to the EU or the European Economic Area (EEA). For both series, data were collected in accordance with the WHO ATC classification system. While the previous series reported data in accordance with the ATC/DDD index 2011, the current series employed the ATC/DDD index 2019. Both series focused on consumption of antibacterials for systemic use (ATC J01) and collected data expressed in DDD per 1000 inhabitants per day and packages per 1000 inhabitants per day. When studying consumption expressed in packages per 1000 inhabitants per day, countries reporting total care data, i.e. community and hospital sector combined, were included in the previous series but excluded in the current series. While the previous series used non-linear mixed models to evaluate time trends in antibiotic consumption, the current series allowed for inclusion of change-points with a data-driven location. In addition, both series assessed the composition and quality of antibiotic consumption in the EU/EEA. CONCLUSIONS: The updated analyses of two decades of ESAC-Net data provide the most comprehensive and detailed description of antibiotic consumption in the community in Europe.


Assuntos
Antibacterianos , Uso de Medicamentos , Antibacterianos/uso terapêutico , Coleta de Dados , Europa (Continente) , União Europeia , Humanos
2.
J Antimicrob Chemother ; 76(12 Suppl 2): ii37-ii44, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312652

RESUMO

OBJECTIVES: Data on quinolone consumption in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of quinolones. METHODS: For the period 1997-2017, data on consumption of quinolones, i.e. ATC group J01M, in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Quinolone consumption was analysed by subgroups based on pharmacokinetic profile, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, quinolone consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 8.2 between countries with the highest (Bulgaria) and the lowest (Norway) consumption. The second-generation quinolones accounted for >50% of quinolone consumption in most countries. Quinolone consumption significantly increased up to 2001, and did not change significantly afterwards. Seasonal variation increased significantly over time. Proportional consumption of third-generation quinolones significantly increased over time relative to that of second-generation quinolones, while proportional consumption of both third- and second-generation quinolones significantly increased relative to that of first-generation quinolones. Levofloxacin and moxifloxacin represented >40% of quinolone consumption in the community in southern EU/EEA countries. CONCLUSIONS: Quinolone consumption in the community is no longer increasing in the EU/EEA, but its seasonal variation continues to increase significantly as is the proportion of quinolones to treat respiratory infections.


Assuntos
Infecções Bacterianas , Quinolonas , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Uso de Medicamentos , Europa (Continente) , União Europeia , Humanos , Pacientes Ambulatoriais
3.
J Antimicrob Chemother ; 76(12 Suppl 2): ii30-ii36, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312653

RESUMO

OBJECTIVES: Data on the consumption of macrolides, lincosamides and streptogramins (MLS) in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in composition of the main subgroups of MLS. METHODS: For the period 1997-2017, data on consumption of MLS, i.e. ATC group J01F, in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of MLS was analysed and presented as trends, seasonal variation, presence of change-points and compositional changes, using a classification based on mean plasma elimination half-life for macrolides. RESULTS: In 2017, consumption of MLS in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 13 between countries with the highest (Greece) and the lowest (Sweden) consumption. Consumption of MLS did not change significantly up to 2003, after which it significantly increased up to 2007. No significant change was observed after 2007. Consumption of MLS showed high seasonal variation. The proportional consumption of long-acting macrolides significantly increased over time compared with that of intermediate-acting macrolides, and proportional consumption of the latter increased compared with that of short-acting macrolides. CONCLUSIONS: Consumption of MLS did not change significantly over time during 2007-2017, while the proportional consumption of long-acting macrolides increased. Seasonal variation remained high, which suggests that MLS are still prescribed inappropriately in many countries.


Assuntos
Macrolídeos , Estreptograminas , Antibacterianos/uso terapêutico , Uso de Medicamentos , União Europeia , Humanos , Lincosamidas
4.
J Antimicrob Chemother ; 76(12 Suppl 2): ii7-ii13, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312654

RESUMO

OBJECTIVES: Data on antibiotic consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main antibiotic groups. METHODS: For the period 1997-2017, data on consumption of antibiotics, i.e. antibacterials for systemic use (ATC group J01), in the community, aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Antibiotic consumption was analysed based on ATC-3 groups, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, antibiotic consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor 3.6 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Antibiotic consumption in the EU/EEA did not change significantly over time. Antibiotic consumption showed a significant seasonal variation, which decreased over time. The number of DDD per package significantly increased over time. The proportional consumption of sulphonamides and trimethoprim (J01E) relative to other groups significantly decreased over time, while the proportional consumption of other antibacterials (J01X) relative to other groups significantly increased over time. CONCLUSIONS: Overall, antibiotic consumption in the community in the EU/EEA did not change during 1997-2017, while seasonal variation consistently decreased over time. The number of DDD per package increased during 1997-2017.


Assuntos
Antibacterianos , Infecções Bacterianas , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Uso de Medicamentos , União Europeia , Humanos , Trimetoprima
5.
J Antimicrob Chemother ; 76(12 Suppl 2): ii79-ii85, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312655

RESUMO

OBJECTIVES: This tutorial describes and illustrates statistical methods to detect time trends possibly including abrupt changes (referred to as change-points) in the consumption of antibiotics in the community. METHODS: For the period 1997-2017, data on consumption of antibacterials for systemic use (ATC group J01) in the community, aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. Trends over time and presence of common change-points were studied through a set of non-linear mixed models. RESULTS: After a thorough description of the set of models used to assess the time trend and presence of common change-points herein, the methodology was applied to the consumption of antibacterials for systemic use (ATC J01) in 25 EU/European Economic Area (EEA) countries. The best fit was obtained for a model including two change-points: one in the first quarter of 2004 and one in the last quarter of 2008. CONCLUSIONS: Allowing for the inclusion of common change-points improved model fit. Individual countries investigating changes in their antibiotic consumption pattern can use this tutorial to analyse their country data.


Assuntos
Antibacterianos , Uso de Medicamentos , Antibacterianos/uso terapêutico , Europa (Continente) , Humanos
6.
J Antimicrob Chemother ; 76(12 Suppl 2): ii60-ii67, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312656

RESUMO

OBJECTIVES: The quality of antibiotic consumption in the community can be assessed using 12 drug-specific quality indicators (DSQIs) developed by the European Surveillance of Antimicrobial Consumption (ESAC) project. We compared quality in 2009 and 2017 in the EU/European Economic Area (EEA) and evaluated the impact of using different DDD values (ATC/DDD indices 2011 and 2019) for the 2009 quality assessment using these DSQIs and a joint scientific opinion (JSO) indicator. METHODS: We calculated the 12 DSQIs and the JSO indicator for 2017 and for 2009 for EU/EEA countries able to deliver values. For each of the indicators we grouped the 2017 and 2009 indicator values into four quartiles. To evaluate changes in quality between 2009 and 2017, we used the quartile distribution of the 2009 indicator values in 30 EU/EEA countries as benchmarks. In addition, we compared the quality assessment for 2009 using the ATC/DDD indices 2011 and 2019. RESULTS: In 2017, a difference in the quality of antibiotic consumption in the community between northern and southern EU/EEA countries remained, but also several eastern EU/EEA countries shifted towards lower quality. Quality of antibiotic consumption decreased between 2009 and 2017 in particular indicator values for penicillin, quinolone, relative ß-lactam and broad- versus narrow-spectrum antibiotic consumption, and seasonal variation. Using different ATC/DDD indices did not substantially change countries' ranking based on their DSQI values. CONCLUSIONS: The quality of antibiotic consumption in the community as measured by the DSQIs further decreased between 2009 and 2017, especially in Southern and Eastern European countries. A continuous effort to improve antibiotic consumption is essential to reduce antibiotic consumption in general and the use of broad-spectrum antibiotics in particular.


Assuntos
Antibacterianos , Quinolonas , Antibacterianos/uso terapêutico , Uso de Medicamentos , Europa (Continente) , União Europeia , Humanos , Penicilinas
7.
J Antimicrob Chemother ; 76(12 Suppl 2): ii14-ii21, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312657

RESUMO

OBJECTIVES: Data on consumption of penicillins in the community were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of penicillins. METHODS: For the period 1997-2017, data on consumption of penicillins, i.e. ß-lactam antibacterials, penicillins (ATC group J01C), in the community aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of penicillins was analysed based on ATC-4 subgroups, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, consumption of penicillins in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 4.9 between countries with the highest (Spain) and the lowest (the Netherlands) consumption. An increase in consumption of penicillins, which was not statistically significant, was observed between 1997 and 2003 and up to 2010. A decrease, which was not statistically significant, was observed from 2010 onwards. Proportional consumption of combinations of penicillins, including ß-lactamase inhibitors (J01CR) increased during 1997-2017, which coincided with a decrease in the proportional consumption of extended-spectrum penicillins (J01CA) and narrow-spectrum penicillins (J01CE). CONCLUSIONS: Considerable variation in the patterns of consumption of penicillins was observed between EU/EEA countries. The consumption of penicillins in the EU/EEA community did not change significantly over time, while the proportional consumption of combinations of penicillins increased.


Assuntos
Antibacterianos , Penicilinas , Antibacterianos/uso terapêutico , Uso de Medicamentos , Europa (Continente) , União Europeia , Humanos , Espanha/epidemiologia
8.
J Antimicrob Chemother ; 76(12 Suppl 2): ii22-ii29, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312658

RESUMO

OBJECTIVES: Data on cephalosporin consumption in the community were collected from 30 EU/EEA countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of the main subgroups of cephalosporins. METHODS: For the period 1997-2017, data on consumption of cephalosporins (i.e. first-, second-, third- and fourth-generation cephalosporins; ATC subgroups J01DB, J01DC, J01DD and J01DE, respectively) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Cephalosporin consumption was analysed based on ATC-4 subgroup, and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, cephalosporin consumption in the community expressed in DDD per 1000 inhabitants per day varied by a factor of 285 between countries with the highest (Greece) and the lowest (the Netherlands) consumption. Cephalosporin consumption did not change significantly between the first quarter of 1997 and the last quarter of 2017. Seasonal variation decreased significantly over time. Proportional consumption of second- and third-generation cephalosporins significantly increased over time compared with that of first-generation cephalosporins, and proportional consumption of fourth-generation cephalosporins significantly decreased compared with that of second- and third-generation cephalosporins. CONCLUSIONS: Despite considerable variation between countries in the composition of cephalosporin consumption and trends over time, a significant shift towards consumption of more broad-spectrum cephalosporins in the community was observed across the EU/EEA during 1997-2017.


Assuntos
Infecções Bacterianas , Cefalosporinas , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Uso de Medicamentos , União Europeia , Humanos , Pacientes Ambulatoriais
9.
J Antimicrob Chemother ; 76(12 Suppl 2): ii68-ii78, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312659

RESUMO

OBJECTIVES: Surveillance of antibiotic consumption in the community is of utmost importance to inform and evaluate control strategies. Data on two decades of antibiotic consumption in the community were collected from 30 EU/European Economic Area (EEA) countries. This article reviews temporal trends and the presence of abrupt changes in subgroups of relevance in antimicrobial stewardship. METHODS: For the period 1997-2017, data on yearly antibiotic consumption in the community, aggregated at the level of the active substance, were collected using the WHO ATC classification and expressed in DDD (ATC/DDD index 2019) per 1000 inhabitants per day. We applied a range of non-linear mixed models to assess the presence of changes in the consumption of antibacterials for systemic use (ATC group J01) and eight antibiotic subgroups. RESULTS: For the majority of the studied groups, a country-specific change-point model provided the best fit. Depending on the antibiotic group/subgroup and on the country, change-points were spread out between 2000 and 2013. CONCLUSIONS: Due to the heterogeneity in antibiotic consumption in the community across EU/EEA countries, a country-specific change-point model provided the better fit. Given the limitations of this model, our recommendation for the included countries is to carefully interpret the country-specific results presented in this article and to use the tutorial included in this series to conduct their own change-point analysis when evaluating the impact of changes in regulations, public awareness campaigns, and other national interventions to improve antibiotic consumption in the community.


Assuntos
Antibacterianos , Uso de Medicamentos , Antibacterianos/uso terapêutico , Europa (Continente) , União Europeia , Humanos
10.
J Antimicrob Chemother ; 76(12 Suppl 2): ii45-ii59, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312660

RESUMO

OBJECTIVES: Data on consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials were collected from 30 EU/European Economic Area (EEA) countries over two decades. This article reviews temporal trends, seasonal variation, presence of change-points and changes in the composition of main subgroups of tetracyclines, sulphonamides and trimethoprim and other antibacterials. METHODS: For the period 1997-2017, data on consumption of tetracyclines (ATC group J01A), sulphonamides and trimethoprim (ATC group J01E), and other antibacterials (ATC group J01X) in the community and aggregated at the level of the active substance, were collected using the WHO ATC/DDD methodology (ATC/DDD index 2019). Consumption was expressed in DDD per 1000 inhabitants per day and in packages per 1000 inhabitants per day. Consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials was analysed based on ATC-4 subgroups and presented as trends, seasonal variation, presence of change-points and compositional changes. RESULTS: In 2017, consumption of tetracyclines, sulphonamides and trimethoprim, and other antibacterials in the community expressed in DDD per 1000 inhabitants per day varied considerably between countries. Between 1997 and 2017, consumption of tetracyclines did not change significantly, while its seasonal variation significantly decreased over time. Consumption of sulphonamides and trimethoprim significantly decreased until 2006, and its seasonal variation significantly decreased over time. The consumption of other antibacterials showed no significant change over time or in seasonal variation. CONCLUSIONS: Consumption and composition of tetracyclines, sulphonamides and trimethoprim, and other antibacterials showed wide variations between EU/EEA countries and over time. This represents an opportunity to further reduce consumption of these groups in some countries and improve the quality of their prescription.


Assuntos
Tetraciclinas , Trimetoprima , Antibacterianos/uso terapêutico , Uso de Medicamentos , União Europeia , Humanos , Sulfonamidas/uso terapêutico , Tetraciclinas/uso terapêutico , Trimetoprima/uso terapêutico
11.
Pharm Stat ; 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34018666

RESUMO

In the meta-analytic surrogate evaluation framework, the trial-level coefficient of determination R trial 2 quantifies the strength of the association between the expected causal treatment effects on the surrogate (S) and the true (T) endpoints. Burzykowski and Buyse supplemented this metric of surrogacy with the surrogate threshold effect (STE), which is defined as the minimum value of the causal treatment effect on S for which the predicted causal treatment effect on T exceeds zero. The STE supplements R trial 2 with a more direct clinically interpretable metric of surrogacy. Alonso et al. proposed to evaluate surrogacy based on the strength of the association between the individual (rather than expected) causal treatment effects on S and T. In the current paper, the individual-level surrogate threshold effect (ISTE) is introduced in the setting where S and T are normally distributed variables. ISTE is defined as the minimum value of the individual causal treatment effect on S for which the lower limit of the prediction interval around the individual causal treatment effect on T exceeds zero. The newly proposed methodology is applied in a case study, and it is illustrated that ISTE has an appealing clinical interpretation. The R package surrogate implements the methodology and a web appendix (supporting information) that details how the analyses can be conducted in practice is provided.

12.
BMC Med Res Methodol ; 21(1): 62, 2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33810785

RESUMO

BACKGROUND: In case-control studies most algorithms allow the controls to be sampled several times, which is not always optimal. If many controls are available and adjustment for several covariates is necessary, matching without replacement might increase statistical efficiency. Comparing similar units when having observational data is of utter importance, since confounding and selection bias is present. The aim was twofold, firstly to create a method that accommodates the option that a control is not resampled, and second, to display several scenarios that identify changes of Odds Ratios (ORs) while increasing the balance of the matched sample. METHODS: The algorithm was derived in an iterative way starting from the pre-processing steps to derive the data until its application in a study to investigate the risk of antibiotics on colorectal cancer in the INTEGO registry (Flanders, Belgium). Different scenarios were developed to investigate the fluctuation of ORs using the combination of exact and varying variables with or without replacement of controls. To achieve balance in the population, we introduced the Comorbidity Index (CI) variable, which is the sum of chronic diseases as a means to have comparable units for drawing valid associations. RESULTS: This algorithm is fast and optimal. We simulated data and demonstrated that the run-time of matching even with millions of patients is minimal. Optimal, since the closest controls is always captured (using the appropriate ordering and by creating some auxiliary variables), and in the scenario that a case has only one control, we assure that this control will be matched to this case, thus maximizing the cases to be used in the analysis. In total, 72 different scenarios were displayed indicating the fluctuation of ORs, and revealing patterns, especially a drop when balancing the population. CONCLUSIONS: We created an optimal and computationally efficient algorithm to derive a matched case-control sample with and without replacement of controls. The code and the functions are publicly available as an open source in an R package. Finally, we emphasize the importance of displaying several scenarios and assess the difference of ORs while using an index to balance population in observational data.


Assuntos
Antibacterianos , Neoplasias Colorretais , Algoritmos , Antibacterianos/uso terapêutico , Bélgica/epidemiologia , Estudos de Casos e Controles , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/epidemiologia , Humanos , Sistema de Registros
13.
Stat Med ; 40(3): 578-592, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33118185

RESUMO

We propose a latent linear mixed model to analyze multivariate longitudinal data of multiple ordinal variables, which are manifestations of fewer continuous latent variables. We focus on the latent level where the effects of observed covariates on the latent variables are of interest. We incorporate serial correlation into the variance component rather than assuming independent residuals. We show that misleading inference may be drawn when misspecifying the variance component. Furthermore, we provide a graphical tool depicting latent empirical semi-variograms to detect serial correlation for latent stationary linear mixed models. We apply our proposed model to examine the treatment effect on patients having the amyotrophic lateral sclerosis disease. The result shows that the treatment can slow down progression of latent cervical and lumbar functions.


Assuntos
Esclerose Amiotrófica Lateral , Esclerose Amiotrófica Lateral/tratamento farmacológico , Humanos , Modelos Lineares , Estudos Longitudinais , Análise Multivariada
14.
Stat Methods Med Res ; 30(3): 747-768, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33256560

RESUMO

In reliability theory, diagnostic accuracy, and clinical trials, the quantity P(X>Y)+1/2P(X=Y), also known as the Probabilistic Index (PI), is a common treatment effect measure when comparing two groups of observations. The quantity P(X>Y)-P(Y>X), a linear transformation of PI known as the net benefit, has also been advocated as an intuitively appealing treatment effect measure. Parametric estimation of PI has received a lot of attention in the past 40 years, with the formulation of the Uniformly Minimum-Variance Unbiased Estimator (UMVUE) for many distributions. However, the non-parametric Mann-Whitney estimator of the PI is also known to be UMVUE in some situations. To understand this seeming contradiction, in this paper a systematic comparison is performed between the non-parametric estimator for the PI and parametric UMVUE estimators in various settings. We show that the Mann-Whitney estimator is always an unbiased estimator of the PI with univariate, completely observed data, while the parametric UMVUE is not when the distribution is misspecified. Additionally, the Mann-Whitney estimator is the UMVUE when observations belong to an unrestricted family. When observations come from a more restrictive family of distributions, the loss in efficiency for the non-parametric estimator is limited in realistic clinical scenarios. In conclusion, the Mann-Whitney estimator is simple to use and is a reliable estimator for the PI and net benefit in realistic clinical scenarios.

15.
Spat Spatiotemporal Epidemiol ; 35: 100379, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33138946

RESUMO

Although COVID-19 has been spreading throughout Belgium since February, 2020, its spatial dynamics in Belgium remain poorly understood, partly due to the limited testing of suspected cases during the epidemic's early phase. We analyse data of COVID-19 symptoms, as self-reported in a weekly online survey, which is open to all Belgian citizens. We predict symptoms' incidence using binomial models for spatially discrete data, and we introduce these as a covariate in the spatial analysis of COVID-19 incidence, as reported by the Belgian government during the days following a survey round. The symptoms' incidence is moderately predictive of the variation in the relative risks based on the confirmed cases; exceedance probability maps of the symptoms' incidence and confirmed cases' relative risks overlap partly. We conclude that this framework can be used to detect COVID-19 clusters of substantial sizes, but it necessitates spatial information on finer scales to locate small clusters.


Assuntos
Infecções por Coronavirus/epidemiologia , Inquéritos Epidemiológicos/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Análise Espacial , Adulto , Idoso , Bélgica/epidemiologia , Betacoronavirus , COVID-19 , Feminino , Inquéritos Epidemiológicos/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Medição de Risco , SARS-CoV-2
16.
Contemp Clin Trials ; 99: 106189, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33132155

RESUMO

Starting from historic reflections, the current SARS-CoV-2 induced COVID-19 pandemic is examined from various perspectives, in terms of what it implies for the implementation of non-pharmaceutical interventions, the modeling and monitoring of the epidemic, the development of early-warning systems, the study of mortality, prevalence estimation, diagnostic and serological testing, vaccine development, and ultimately clinical trials. Emphasis is placed on how the pandemic had led to unprecedented speed in methodological and clinical development, the pitfalls thereof, but also the opportunities that it engenders for national and international collaboration, and how it has simplified and sped up procedures. We also study the impact of the pandemic on clinical trials in other indications. We note that it has placed biostatistics, epidemiology, virology, infectiology, and vaccinology, and related fields in the spotlight in an unprecedented way, implying great opportunities, but also the need to communicate effectively, often amidst controversy.


Assuntos
Pesquisa Biomédica/organização & administração , Bioestatística/métodos , COVID-19/epidemiologia , Métodos Epidemiológicos , Fatores Etários , Pesquisa Biomédica/normas , COVID-19/mortalidade , Teste para COVID-19/métodos , Teste para COVID-19/normas , Vacinas contra COVID-19 , Causas de Morte , Controle de Doenças Transmissíveis/organização & administração , Desenvolvimento de Medicamentos/organização & administração , Indústria Farmacêutica/organização & administração , Determinação de Ponto Final/normas , Europa (Continente) , Comunicação em Saúde/normas , Humanos , Imunidade Coletiva/fisiologia , Modelos Teóricos , Pandemias , Prevalência , Opinião Pública , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , SARS-CoV-2 , Estações do Ano , Fatores Sexuais , Fatores de Tempo
17.
Biometrics ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33128231

RESUMO

Given the heterogeneous responses to therapy and the high cost of treatments, there is an increasing interest in identifying pretreatment predictors of therapeutic effect. Clearly, the success of such an endeavor will depend on the amount of information that the patient-specific variables convey about the individual causal treatment effect on the response of interest. In the present work, using causal inference and information theory, a strategy is proposed to evaluate individual predictive factors for cancer immunotherapy efficacy. In a first step, the methodology proposes a causal inference model to describe the joint distribution of the pretreatment predictors and the individual causal treatment effect. Further, in a second step, the so-called predictive causal information (PCI), a metric that quantifies the amount of information the pretreatment predictors convey on the individual causal treatment effects, is introduced and its properties are studied. The methodology is applied to identify predictors of therapeutic success for a therapeutic vaccine in advanced lung cancer. A user-friendly R library EffectTreat is provided to carry out the necessary calculations.

18.
Stat Med ; 39(26): 3867-3878, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-32875590

RESUMO

The relationship between association and surrogacy has been the focus of much debate in the surrogate marker literature. Recently, the individual causal association (ICA) has been introduced as a metric of surrogacy in the causal inference framework, when both the surrogate and the true endpoint are normally distributed and when both are binary. Earlier work on the normal case has demonstrated that, although the ICA and the adjusted association are related metrics, their relationship strongly depends on unidentifiable parameters and, consequently, the association between both endpoints conveys little information on the validity of the surrogate. In addition, in the normal setting, the magnitude of the ICA does not depend on the mean of the outcomes. The latter implies that identifiable parameters such as mean responses and treatment effects provide no information on the validity of the surrogate. In the present work it is shown that this is fundamentally different in the binary case. We demonstrate that the observed association between the outcomes as well as the success rates in both treatment groups are quite predictive for the ICA. It is shown that finding a good surrogate will be more likely when the association between the endpoints is large, there are sizeable treatment effects and the success rates for both endpoints are similar in both treatment groups. These results are demonstrated using extensive simulations and illustrated on a case study in multi-drug resistant tuberculosis.


Assuntos
Biomarcadores , Determinação de Ponto Final , Modelos Estatísticos , Humanos
19.
BMC Cancer ; 20(1): 772, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807114

RESUMO

BACKGROUND: Immunosenescence biomarkers and peripheral blood parameters are evaluated separately as possible predictive markers of immunotherapy. Here, we illustrate the use of a causal inference model to identify predictive biomarkers of CIMAvaxEGF success in the treatment of Non-Small Cell Lung Cancer Patients. METHODS: Data from a controlled clinical trial evaluating the effect of CIMAvax-EGF were analyzed retrospectively, following a causal inference approach. Pre-treatment potential predictive biomarkers included basal serum EGF concentration, peripheral blood parameters and immunosenescence biomarkers. The proportion of CD8 + CD28- T cells, CD4+ and CD8+ T cells, CD4/CD8 ratio and CD19+ B cells. The 33 patients with complete information were included. The predictive causal information (PCI) was calculated for all possible models. The model with a minimum number of predictors, but with high prediction accuracy (PCI > 0.7) was selected. Good, rare and poor responder patients were identified using the predictive probability of treatment success. RESULTS: The mean of PCI increased from 0.486, when only one predictor is considered, to 0.98 using the multivariate approach with all predictors. The model considering the proportion of CD4+ T cell, basal Epidermal Growth Factor (EGF) concentration, neutrophil to lymphocyte ratio, Monocytes, and Neutrophils as predictors were selected (PCI > 0.74). Patients predicted as good responders according to the pre-treatment biomarkers values treated with CIMAvax-EGF had a significant higher observed survival compared with the control group (p = 0.03). No difference was observed for bad responders. CONCLUSIONS: Peripheral blood parameters and immunosenescence biomarkers together with basal EGF concentration in serum resulted in good predictors of the CIMAvax-EGF success in advanced NSCLC. Future research should explore molecular and genetic profile as biomarkers for CIMAvax-EGF and it combination with immune-checkpoint inhibitors. The study illustrates the application of a new methodology, based on causal inference, to evaluate multivariate pre-treatment predictors. The multivariate approach allows realistic predictions of the clinical benefit of patients and should be introduced in daily clinical practice.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/sangue , Vacinas Anticâncer/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/terapia , Modelos Estatísticos , Idoso , Biomarcadores Tumorais/imunologia , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Ensaios Clínicos Fase III como Assunto , Terapia Combinada/métodos , Fator de Crescimento Epidérmico/sangue , Fator de Crescimento Epidérmico/imunologia , Feminino , Humanos , Imunossenescência , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos
20.
Eur Heart J Acute Cardiovasc Care ; 9(3): 204-208, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32352314

RESUMO

COVID-19 has developed into a pandemic, hitting hard on our communities. As the pandemic continues to bring health and economic hardship, keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The course of an epidemic may be defined by a series of key factors. In the early stages of a new infectious disease outbreak, it is crucial to understand the transmission dynamics of the infection. The basic reproduction number (R0), which defines the mean number of secondary cases generated by one primary case when the population is largely susceptible to infection ('totally naïve'), determines the overall number of people who are likely to be infected, or, more precisely, the area under the epidemic curve. Estimation of changes in transmission over time can provide insights into the epidemiological situation and identify whether outbreak control measures are having a measurable effect. For R0 > 1, the number infected tends to increase, and for R0 < 1, transmission dies out. Non-pharmaceutical strategies to handle the epidemic are sketched and based on current knowledge, the current situation is sketched and scenarios for the near future discussed.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Surtos de Doenças/prevenção & controle , Controle de Infecções/tendências , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Insuficiência Respiratória/terapia , Doença Aguda , Número Básico de Reprodução , Betacoronavirus , COVID-19 , Controle de Doenças Transmissíveis , Infecções por Coronavirus/transmissão , Transmissão de Doença Infecciosa/classificação , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Hipóxia/etiologia , Pandemias , Pneumonia Viral/transmissão , Respiração Artificial/métodos , Insuficiência Respiratória/etiologia , SARS-CoV-2 , Latência Viral/fisiologia
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