Cost-Effectiveness of Screening for Open Angle Glaucoma Compared With Opportunistic Case Finding.

PRCIS: The manuscript evaluates cost-effectiveness of glaucoma screening with imaging devices and telemedicine based on a screening campaign performed in Spain. The screening strategy implemented in our analysis was cost-effective compared with opportunistic case finding. INTRODUCTION: Open angle glaucoma is an asymptomatic ocular disease that represents one of the first causes of blindness. Diagnosis is currently made by opportunistic case finding, usually by community optometrists or general ophthalmologists. The aim of this study was to assess the cost-effectiveness of a screening strategy based on optical coherence tomography and fundus photographs in glaucoma detection. MATERIALS AND METHODS: A cost-effectiveness analysis was carried out to compare 2 alternative strategies: opportunistic finding versus screening. A Markov tree model was carried out with 10 health states according to disease progression. Quality-adjusted life years (QALYs) were used as a measure of effectiveness. We included short-term and long-term direct health costs and a discount rate of 3%. We performed a probabilistic sensitivity analysis and several 1-way sensitivity analyses. RESULTS: The cohort in the screening program entailed an increase in 0.097 QALYs and additional costs of €1187 versus opportunistic finding, with an incremental cost-effectiveness ratio of about €12.214/QALY. The 1-way sensitivity analysis showed that inputs related to age and screening program (cost and detection rate) were those most strongly influencing the results of the analysis. Probabilistic sensitivity analyses showed that the model was robust to significant changes in the main variables of the analysis. CONCLUSIONS: The screening strategy implemented in our analysis was cost-effective compared with opportunistic finding in patients with glaucoma in this Spanish setting.

International ring trial to validate a new method for testing the antimicrobial efficacy of domestic laundry products.

Due to greater environmental awareness, domestic laundry habits are changing, and antimicrobial control by chemical methods has become an essential factor to compensate for the use of lower temperatures during washing machine cycles. Disinfectants added to laundry detergents are a preventive strategy to reduce the transmission of bacteria, fungi, and viruses in the home, correct aesthetic damage (e.g., spotting, discolouration, and staining), and control the microbial contamination that leads to malodour. In Europe, disinfectants are regulated by the EU Biocidal Products Regulation (No. 528/2012), which stipulates that antimicrobial efficacy must be evaluated according to standardized methods. Current European standards for laundry sanitization only apply to clinical settings (EN 16616: 2015) and are restricted to the main wash cycle. Therefore, there is a gap in the EU standards regarding the testing of product efficacy in household laundering. With the aim of addressing this gap, an international ring trial was organized to evaluate the robustness of a new method (prEN 17658) designed to test the efficacy of antimicrobial laundry products in a domestic setting. The seven participating laboratories were equipped with 5 different laboratory-scale devices to simulate the washing process, and they evaluated 7 microbial parameters for 2 experimental conditions and 3 levels of active substance. The analysis of data according to ISO 5725-2 and ISO 13528 demonstrated that the method was robust. All reproducibility standard deviation values were between 0.00 and 1.40 and the relative standard deviation indicates satisfactory reproducibility. Values of logarithmic reduction ranged from less than 2 log10 for tests with water to more than 5 log10 when disinfectants were added. The evidence generated by the ring trial was presented in a proposal for a standardized method under CEN/TC 216, in which the SOP used in the ring trial is referred to as the prEN 17658 phase 2 step 2 test method covering chemothermal textile disinfection in domestic settings.

Automatic detection and quantification of floating marine macro-litter in aerial images: Introducing a novel deep learning approach connected to a web application in R.

The threats posed by floating marine macro-litter (FMML) of anthropogenic origin to the marine fauna, and marine ecosystems in general, are universally recognized. Dedicated monitoring programmes and mitigation measures are in place to address this issue worldwide, with the increasing support of new technologies and the automation of analytical processes. In the current study, we developed algorithms capable of detecting and quantifying FMML in aerial images, and a web-oriented application that allows users to identify FMML within images of the sea surface. The proposed algorithm is based on a deep learning approach that uses convolutional neural networks (CNNs) capable of learning from unstructured or unlabelled data. The CNN-based deep learning model was trained and tested using 3723 aerial images (50% containing FMML, 50% without FMML) taken by drones and aircraft over the waters of the NW Mediterranean Sea. The accuracies of image classification (performed using all the images for training and testing the model) and cross-validation (performed using 90% of images for training and 10% for testing) were 0.85 and 0.81, respectively. The Shiny package of R was then used to develop a user-friendly application to identify and quantify FMML within the aerial images. The implementation of this, and similar algorithms, allows streamlining substantially the detection and quantification of FMML, providing support to the monitoring and assessment of this environmental threat. However, the automated monitoring of FMML in the open sea still represents a technological challenge, and further research is needed to improve the accuracy of current algorithms.

A priori estimation of sequencing effort in complex microbial metatranscriptomes.

Metatranscriptome analysis or the analysis of the expression profiles of whole microbial communities has the additional challenge of dealing with a complex system with dozens of different organisms expressing genes simultaneously. An underlying issue for virtually all metatranscriptomic sequencing experiments is how to allocate the limited sequencing budget while guaranteeing that the libraries have sufficient depth to cover the breadth of expression of the community. Estimating the required sequencing depth to effectively sample the target metatranscriptome using RNA-seq is an essential first step to obtain robust results in subsequent analysis and to avoid overexpansion, once the information contained in the library reaches saturation. Here, we present a method to calculate the sequencing effort using a simulated series of metatranscriptomic/metagenomic matrices. This method is based on an extrapolation rarefaction curve using a Weibull growth model to estimate the maximum number of observed genes as a function of sequencing depth. This approach allowed us to compute the effort at different confidence intervals and to obtain an approximate a priori effort based on an initial fraction of sequences. The analytical pipeline presented here may be successfully used for the in-depth and time-effective characterization of complex microbial communities, representing a useful tool for the microbiome research community.

Impact of treated sewage effluent on the bacterial community composition in an intermittent mediterranean stream.

Water quality monitoring is essential to safeguard human and environmental health. The advent of next-generation sequencing techniques in recent years, which allow a more in-depth study of environmental microbial communities in the environment, could broaden the perspective of water quality monitoring to include impact of faecal pollution bacteria on ecosystem. In this study, 16 S rRNA amplicon sequencing was used to evaluate the impact of wastewater treatment plant (WWTP) effluent on autochthonous microbial communities of a temporary Mediterranean stream characterized by high flow seasonality (from 0.02 m3/s in winter to 0.006 m3/s in summer). Seven sampling campaigns were performed under different temperatures and streamflow conditions (winter and summer). Water samples were collected upstream (Upper) of the WWTP, the secondary effluent (EF) discharge and 75 m (P75) and 1000 m (P1000) downstream of the WWTP. A total of 5,593,724 sequences were obtained, giving rise to 20,650 amplicon sequence variants (ASV), which were further analysed and classified into phylum, class, family and genus. Each sample presented different distribution and abundance of taxa. Although taxon distribution and abundance differed in each sample, the microbial community structure of P75 resembled that of EF samples, and Upper and P1000 samples mostly clustered together. Alpha diversity showed the highest values for Upper and P1000 samples and presented seasonal differences, being higher in winter conditions of high streamflow and low temperature. Our results suggest the microbial ecology re-establishment, since autochthonous bacterial communities were able to recover from the impact of the WWTP effluent in 1 km. Alpha diversity results indicates a possible influence of environmental factors on the bacterial community structure. This study shows the potential of next-generation sequencing techniques as useful tools in water quality monitoring and management within the climate change scenario.

Statistical Methods for Quality Equivalence of Topical Products. 0.5 mg/g Betamethasone Ointment as a Case-Study.

This study examines the statistical implications, and their possible implementation, of the "Draft guideline on quality and equivalence of topical products" issued by the European Medicines Agency in 2018, with particular focus on the section devoted to quality equivalence of physical properties. A new confidence interval to conduct the quality equivalence test and a way to cope with the multiplicity of quality parameters are presented and discussed. As an example, the results and the statistical analysis of a study on betamethasone 0.5 mg/g ointment are presented. It is suggested that the equivalence limits proposed in the draft guideline are overly strict: It is as difficult to declare quality equivalence between two packaging formats of the same reference product as to declare quality equivalence between the reference and the test product.

Biodiversity analysis of true bug assemblages (Hemiptera, Heteroptera) in four habitats in the Garraf Natural Park (Barcelona, Spain).

With the aim of gaining insight into true bugs assemblages, and of giving tools to enhance environmental manager tasks, an analysis was made of the alpha and beta diversity of true bug assemblages in the NE Iberian Peninsula. The study took place during the years 1999, 2000, and 2001. The diversity of true bug assemblages among four typical Mediterranean plant communities (dry grassland, calcicolous rosemary scrub, kermes oak scrub, and evergreen oak forest) in a protected natural area was compared. In each plant community, a stratified sampling, taking into account plants with highest coverage percentage, was performed. Collections were performed monthly using direct observation plus beating or sweeping of the entomological net. Objectives were 1) to assess whether true bug assemblages are different in each plant community surveyed, by means of the analysis of their alpha and beta diversity, 2) to assess if any of the four true bug assemblages may be prioritized according to the biodiversity parameters studied. In total, 3,071 specimens, belonging to 12 families and 77 species were identified. Fifty percent of specimens collected belonged to only three species, and ∼33% of species was represented by only one or two individuals. In each Heteroptera assemblage, the distribution pattern of species frequency classes followed a lognormal model. Thirty-five percent of species represented by three or more specimens were found in only one plant community. Abundance, species richness, and diversity were found to be different for each true bug assemblage and along the year. Abundance was highest in the evergreen oak forest and in spring. Species richness and diversity were highest in the kermes oak scrub and in early summer. Nonparametric species richness estimators showed that completeness of species inventory was >80%. In the study zone, true bug diversity may be considered low medium. Our results show that true bugs assemblages are characteristic of specific plant communities, and thus, true bugs fit as candidate monitoring group in environmental and conservation management.

Uso de la simulación en la investigación clínica / Use of the simulation in the clinical investigation

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El desajuste paciente-prótesis moderado no aumenta de modo independiente la mortalidad a 30 días tras la sustitución aislada de válvula aórtica / Moderate patient-prosthesis mismatch has no independent effect on 30-day mortality after isolated aortic valve replacement

Introducción y objetivos. La cuestión de si un desajuste paciente-prótesis moderado tras la sustitución aislada de la válvula aórtica puede aumentar la mortalidad a 30 días continúa abierta. El objetivo de este estudio es verificar si un desajuste moderado es un factor predictivo de carácter independiente respecto a la mortalidad temprana total o cardiaca tras la sustitución valvular aórtica. Métodos. Formaron la población del estudio 272 adultos (mediana de edad, 72 años; intervalo intercuartílico, 66-76 años) a los que se practicaron intervenciones de sustitución aislada de la válvula aórtica. Se consideró que había un desajuste moderado si el área efectiva del orificio indexada que se preveía era ≤ 0,85 y > 0,65 cm2/m2. Se consideró que había un desajuste grave si el área efectiva del orificio indexada prevista era ≤ 0,65 cm2/m2. El seguimiento a 30 días respecto a la supervivencia se cumplió en el 100% de los casos. Resultados. Se detectó un desajuste moderado en el 37,9% de los pacientes. No hubo ningún caso de desajuste grave. Un análisis multivariable identificó los siguientes factores predictivos independientes para la mortalidad total a 30 días: fracción de eyección ventricular izquierda < 50% (p = 0,03) y edad (p = 0,01). Las mismas variables pero con un mayor nivel de significación estadística eran factores predictivos de la supervivencia por causas cardiacas a 30 días: fracción de eyección ventricular izquierda < 50% (p = 0,006) y edad (p = 0,008). Nuestro análisis no identificó que el desajuste moderado fuera un factor predictivo de la mortalidad total o cardiaca a 30 días en nuestra muestra de estudio. Conclusiones. Nuestros resultados indican que la evidencia de que la implantación de la prótesis del tamaño medido en un anillo aórtico pequeño compromete la supervivencia del paciente está lejos de ser clara cuando el desajuste paciente-prótesis es moderado (AU)

Introduction and objectives. It is still not clear whether the presence of a moderate patient-prosthesis mismatch after isolated aortic valve replacement can increase 30-day mortality. The aim of this study was to determine whether a moderate mismatch is an independent predictor of early global or cardiac mortality after aortic valve replacement. Methods. The study involved 272 adult patients (median age, 72 years; interquartile range, 66-76 years) undergoing isolated aortic valve replacement. Moderate mismatch was considered to be present if the projected indexed effective orifice area was ≤0.85 and >0.65 cm2/m2. Severe mismatch was present if the projected indexed effective orifice area was ≤0.65 cm2/m2. Follow-up to assess survival at 30 days was carried out in 100% of patients. Results. Moderate mismatch was observed in 37.9% of patients. None had a severe mismatch. Multivariate analysis identified the following independent predictors of global mortality at 30 days: left ventricular ejection fraction <50 p=".01)." and age the same variables were identified as predictors of 30-day cardiac survival but at a higher level statistical significance: left ventricular ejection fraction <50 p=".008)." and age the analysis did not identify moderate mismatch as a predictor of global or cardiac 30-day mortality in our study population conclusions findings indicate that evidence inserting prosthesis measured size small aortic annulus compromises patient s survival is far from clear when patient-prosthesis (AU)

[Moderate patient-prosthesis mismatch has no independent effect on 30-day mortality after isolated aortic valve replacement]. / El desajuste paciente-prótesis moderado no aumenta de modo independiente la mortalidad a 30 días tras la sustitución aislada de válvula aórtica.

INTRODUCTION AND OBJECTIVES: It is still not clear whether the presence of a moderate patient-prosthesis mismatch after isolated aortic valve replacement can increase 30-day mortality. The aim of this study was to determine whether a moderate mismatch is an independent predictor of early global or cardiac mortality after aortic valve replacement. METHODS: The study involved 272 adult patients (median age, 72 years; interquartile range, 66-76 years) undergoing isolated aortic valve replacement. Moderate mismatch was considered to be present if the projected indexed effective orifice area was < or =0.85 and >0.65 cm2/m2. Severe mismatch was present if the projected indexed effective orifice area was < or =0.65 cm2/m2. Follow-up to assess survival at 30 days was carried out in 100% of patients. RESULTS: Moderate mismatch was observed in 37.9% of patients. None had a severe mismatch. Multivariate analysis identified the following independent predictors of global mortality at 30 days: left ventricular ejection fraction <50% (P=.03) and age (P=.01). The same variables were identified as predictors of 30-day cardiac survival, but at a higher level of statistical significance: left ventricular ejection fraction <50% (P=.006) and age (P=.008). The analysis did not identify moderate mismatch as a predictor of global or cardiac 30-day mortality in our study population. CONCLUSIONS: Our findings indicate that the evidence that inserting a prosthesis of the measured size in a small aortic annulus compromises the patient's survival is far from clear when the patient-prosthesis mismatch is moderate.

A graphical study of tuberculosis incidence and trends in the WHO's European region (1980-2006).

A graphical output was obtained using classical principal component analysis techniques in order to analyse tuberculosis trends in Europe over a 27-year period (1980-2006). Taxonomic methods were used to better define the interrelationship between the data in the 52 countries studied. Data were provided by the World Health Organization. Differences in the overall incidence and trends were identified during the 1980-2006 period. The highest rates of incidence were reported in Kazakhstan, Bosnia and Herzegovina, Romania and Kyrgyzstan. High and moderately high rates were reported in the former Soviet Union, the former Yugoslavia, some countries from the former Eastern Bloc, Turkey and Portugal. The lowest rates were reported in the eastern Mediterranean, Scandinavia and Iceland. Risk of infection was determined by social conditions, intravenous drug use, HIV infection and immigration from countries where tuberculosis is endemic. As regards development of tuberculosis in Europe, 1992 represents the change in the decreasing trend in the incidence observed from 1980, when the incidence presented a minimum general trend and started to increase. The linear model calculated to project the rate of increase from 2006 to 2015, reveals the tuberculosis rates observed during the 1980s.

[Sequential designs and intermediate analysis in clinical research: size vs difficulty]. / Diseños secuenciales y análisis intermedio en la investigación clínica: tamaño frente a dificultad.

Sequential design differs from other statistical designs used in clinical research in that the sample size is not fixed in advance but it varies depending on the results obtained. The intermediate analysis is defined as the treatment evaluation during an initial stage of the study and may lead to the termination of the study. Treatment effect with respect to control is evaluated across a series of pre-established time intervals. The study should be halted if there are significant differences in the level of overall significance, alpha. If this does not happen, then the study continues until reaching a maximum sample size, n, at which point the study ends and the hypothesis of equality is accepted. In general, sequential designs require fewer patients, although they make the study more complex because there is a need for continuous information about the patients' status; this latter aspect requires greater effort in terms of both study monitoring and patient follow-up. The aim therefore is to find a balance between smaller sample size (n) and greater complexity.

Diseños secuenciales y análisis intermedio en la investigación clínica: tamaño frente a dificultad / Sequential designs and intermediate analysis in clinical research: size vs difficulty

A diferencia de otros diseños estadısticos utilizados en la investigación clínica, en el diseño secuencial no se fija el tamaño muestral previamente, sino que éste varía en función de los resultados que se van obteniendo. El análisis intermedio se define como la evaluación del tratamiento durante una etapa inicial del estudio y puede conducir a la finalización del estudio. El efecto del tratamiento respecto al control se evaluará durante una serie de intervalos de tiempo prefijados. Se deberá detener el estudio si hay diferencias estadísticamente significativas en el nivel designificación global a; en caso contrario se continuará con el estudio hasta llegar a un tamaño (...) (AU)

Sequential design differs from other statistical designs used in clinical research in that the sample size is not fixed in advance but it varies depending on the results obtained. The intermediate analysis is defined as the treatment evaluation during an initial stage of the study and may lead to the termination of the study. Treatment effect with respect to control is evaluated across a series of pre-established time intervals. The study should be halted if there are significant differences in the level of overall significance, α. If this does not happen, then the study continues until reaching a maximum sample size, n, at which point the study ends and the hypothesis of equality is accepted. In general, sequential designs require fewer patients, although they make the study more complex because there is a need for continuous information about the patients’ status; this latter aspect requires greater effort in terms of both study monitoring and patient follow-up. The aim therefore is to find a balance between smaller sample size (n) and greater complexity (AU)

Simulación como herramienta de optimización de la investigación clínica / Simulation as an optimization tool in clinical research

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