Epidemiology of reported cases of leptospirosis in the EU/EEA, 2010 to 2021.

BackgroundLeptospirosis is a zoonotic disease caused by bacteria of the genus Leptospira. Humans are infected by exposure to animal urine or urine-contaminated environments. Although disease incidence is lower in Europe compared with tropical regions, there have been reports of an increase in leptospirosis cases since the 2000s in some European countries.AimWe aimed to describe the epidemiology of reported cases of leptospirosis in the European Union/European Economic Area (EU/EEA) during 2010-2021 and to identify potential changes in epidemiological patterns.MethodsWe ran a descriptive analysis of leptospirosis cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease during 2010-2021. We also analysed trends at EU/EEA and national level.ResultsDuring 2010-2021, 23 countries reported 12,180 confirmed leptospirosis cases corresponding to a mean annual notification rate of 0.24 cases per 100,000 population. Five countries (France, Germany, the Netherlands, Portugal and Romania) accounted for 79% of all reported cases. The highest notification rate was observed in Slovenia with 0.82 cases per 100,000 population. Overall, the notification rate increased by 5.0% per year from 2010 to 2021 (95% CI: 1.2-8.8%), although trends differed across countries.ConclusionThe notification rate of leptospirosis at EU/EEA level increased during 2010-2021 despite including the first 2 years of the COVID-19 pandemic and associated changes in population behaviours. Studies at (sub)national level would help broaden the understanding of differences at country-level and specificities in terms of exposure to Leptospira, as well as biases in diagnosis and reporting.

TRANSPLANTATION OF SUBRETINAL STEM CELL-DERIVED RETINAL PIGMENT EPITHELIUM FOR STARGARDT DISEASE: A Phase I Clinical Trial.

PURPOSE: To assess the safety of injecting human embryonic stem cell retinal pigment epithelial cell dose to treat Stargardt disease. METHODS: In this prospective, Phase I clinical trial, human embryonic stem cell retinal pigment epithelial cells in suspension were injected into the subretinal space in eyes with the worse best-corrected visual acuity (BCVA). After vitrectomy/posterior hyaloid removal, a partial retinal detachment was created and the human embryonic stem cell retinal pigment epithelial cells were administered. Phacoemulsification with intraocular lens implantation was performed in eyes with lens opacity. All procedures were optical coherence tomography-guided. The 12-month follow-up included retinal imaging, optical coherence tomography, visual field/electrophysiologic testing, and systemic evaluation. The main outcome was the absence of ocular/systemic inflammation or rejection, tumor formation, or toxicity during follow-up. RESULTS: The mean baseline BCVAs in the phacoemulsification and no phacoemulsification groups were similar (1.950 ± 0.446 and 1.575 ± 0.303, respectively). One year postoperatively, treated eyes showed a nonsignificant increase in BCVA. No adverse effects occurred during follow-up. Intraoperative optical coherence tomography was important for guiding all procedures. CONCLUSION: This surgical procedure was feasible and safe without cellular migration, rejection, inflammation, or development of ocular or systemic tumors during follow-up.

Microorganisms that produce enzymes active on biodegradable polyesters are ubiquitous.

Biodegradability standards measure ultimate biodegradation of polymers by exposing the material under test to a natural microbial inoculum. Available tests developed by the International Organization for Standardization (ISO) use inoculums sampled from different environments e.g. soil, marine sediments, seawater. Understanding whether each inoculum is to be considered as microbially unique or not can be relevant for the interpretation of tests results. In this review, we address this question by consideration of the following: (i) the chemical nature of biodegradable plastics (virtually all biodegradable plastics are polyesters) (ii) the diffusion of ester bonds in nature both in simple molecules and in polymers (ubiquitous); (iii) the diffusion of decomposers capable of producing enzymes, called esterases, which accelerate the hydrolysis of esters, including polyesters (ubiquitous); (iv) the evidence showing that synthetic polyesters can be depolymerized by esterases (large and growing); (v) the evidence showing that these esterases are ubiquitous (growing and confirmed by bioinformatics studies). By combining the relevant available facts it can be concluded that if a certain polyester shows ultimate biodegradation when exposed to a natural inoculum, it can be considered biodegradable and need not be retested using other inoculums. Obviously, if the polymer does not show ultimate biodegradation it must be considered recalcitrant, until proven otherwise.

Age-specific associations between underlying health conditions and hospitalisation, death and in-hospital death among confirmed COVID-19 cases: a multi-country study based on surveillance data, June to December 2020.

BackgroundUnderlying conditions are risk factors for severe COVID-19 outcomes but evidence is limited about how risks differ with age.AimWe sought to estimate age-specific associations between underlying conditions and hospitalisation, death and in-hospital death among COVID-19 cases.MethodsWe analysed case-based COVID-19 data submitted to The European Surveillance System between 2 June and 13 December 2020 by nine European countries. Eleven underlying conditions among cases with only one condition and the number of underlying conditions among multimorbid cases were used as exposures. Adjusted odds ratios (aOR) were estimated using 39 different age-adjusted and age-interaction multivariable logistic regression models, with marginal means from the latter used to estimate probabilities of severe outcome for each condition-age group combination.ResultsCancer, cardiac disorder, diabetes, immunodeficiency, kidney, liver and lung disease, neurological disorders and obesity were associated with elevated risk (aOR: 1.5-5.6) of hospitalisation and death, after controlling for age, sex, reporting period and country. As age increased, age-specific aOR were lower and predicted probabilities higher. However, for some conditions, predicted probabilities were at least as high in younger individuals with the condition as in older cases without it. In multimorbid patients, the aOR for severe disease increased with number of conditions for all outcomes and in all age groups.ConclusionWhile supporting age-based vaccine roll-out, our findings could inform a more nuanced, age- and condition-specific approach to vaccine prioritisation. This is relevant as countries consider vaccination of younger people, boosters and dosing intervals in response to vaccine escape variants.

Hepatitis of unknown aetiology in children - epidemiological overview of cases reported in Europe, 1 January to 16 June 2022.

Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epidemiological, clinical and microbiological data available in TESSy. Of the reported cases, 77.3% were 5 years or younger and 53.5% had a positive test for adenovirus, 10.4% had a positive RT-PCR for SARS-CoV-2 and 10.3% were coinfected with both pathogens. Cases with adenovirus infections were significantly more likely to be admitted to intensive care or high-dependency units (OR = 2.11; 95% CI: 1.18-3.74) and transplanted (OR = 3.36; 95% CI: 1.19-9.55) than cases with a negative test result for adenovirus, but this was no longer observed when looking at this association separately between the UK and other countries. Aetiological studies are needed to ascertain if adenovirus plays a role in this possible emergence of hepatitis cases in children and, if confirmed, the mechanisms that could be involved.

Initial assessment of the COVID-19 vaccination's impact on case numbers, hospitalisations and deaths in people aged 80 years and older, 15 EU/EEA countries, December 2020 to May 2021.

Prioritisation of elderly people in COVID-19 vaccination campaigns aimed at reducing severe outcomes in this group. Using EU/EEA surveillance and vaccination uptake, we estimated the risk ratio of case, hospitalisation and death notifications in people 80 years and older compared with 25-59-year-olds. Highest impact was observed for full vaccination uptake 80% or higher with reductions in notification rates of cases up to 65% (IRR: 0.35; 95% CI: 0.13-0.99), hospitalisations up to 78% (IRR: 0.22; 95% CI: 0.13-0.37) and deaths up to 84% (IRR: 0.16; 95% CI: 0.13-0.20).

Relative efficiencies of two-stage sampling schemes for mean estimation in multilevel populations when cluster size is informative.

In multilevel populations, there are two types of population means of an outcome variable ie, the average of all individual outcomes ignoring cluster membership and the average of cluster-specific means. To estimate the first mean, individuals can be sampled directly with simple random sampling or with two-stage sampling (TSS), that is, sampling clusters first, and then individuals within the sampled clusters. When cluster size varies in the population, three TSS schemes can be considered, ie, sampling clusters with probability proportional to cluster size and then sampling the same number of individuals per cluster; sampling clusters with equal probability and then sampling the same percentage of individuals per cluster; and sampling clusters with equal probability and then sampling the same number of individuals per cluster. Unbiased estimation of the average of all individual outcomes is discussed under each sampling scheme assuming cluster size to be informative. Furthermore, the three TSS schemes are compared in terms of efficiency with each other and with simple random sampling under the constraint of a fixed total sample size. The relative efficiency of the sampling schemes is shown to vary across different cluster size distributions. However, sampling clusters with probability proportional to size is the most efficient TSS scheme for many cluster size distributions. Model-based and design-based inference are compared and are shown to give similar results. The results are applied to the distribution of high school size in Italy and the distribution of patient list size for general practices in England.

Carriage rates and risk factors during an outbreak of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11) in Tuscany, Italy: a cross-sectional study.

BACKGROUND: During 2015-2016 an outbreak of invasive meningococcal disease due to N. meningitidis serogroup C ST-11 (cc11) occurred in Tuscany, Italy. The outbreak affected mainly the age group 20-30 years, men who have sex with men, and the area located between the cities of Firenze, Prato and Empoli, with discos and gay-venues associated-clusters. A cross-sectional-survey was conducted to assess the prevalence and risk factors for meningococcal-carriage, in order to address public health interventions. METHODS: A convenience sample of people aged 11-45 years provided oropharyngeal swab specimens and completed questionnaires on risk factors for meningococcal carriage during a 3 months study-period, conducted either in the outbreak-area and in a control-area not affected by the outbreak (cities of Grosseto and Siena). Isolates were tested by culture plus polymerase chain reaction. Serogroup C meningococcal isolates were further characterized using multilocus sequence typing. Univariate and multivariate analyses were performed to estimate adjusted odds ratios (AORs) for meningococcal carriage. RESULTS: A total of 2285 oropharyngeal samples were collected. Overall, meningococcal carriage prevalence was 4.8% (n = 110), with nonencapsulated meningococci most prevalent (2.3%; n = 52). Among encapsulated meningococci, serogroup B was the most prevalent (1.8%; n = 41), followed by serogroup Y (0.5%; n = 11) and serogroup C (0.2%; n = 4); one carrier of serogroup E and one of serogroup Z, were also found (0.04%). Three individuals from the city of Empoli were found to carry the outbreak strain, C:ST-11 (cc11); this city also had the highest serogroup C carriage prevalence (0.5%). At the multivariate analyses, risk factors for meningococcal carriage were: illicit-drugs consumption (AOR 6.30; p < 0.01), active smoking (AOR 2.78; p = 0.01), disco/clubs/parties attendance (AOR 2.06; p = 0.04), being aged 20-30 years (AOR 3.08; p < 0.01), and have had same-sex intercourses (AOR 6.69; p < 0.01). CONCLUSIONS: A low prevalence of meningococcal serogroup C carriage in an area affected by an outbreak due to the hypervirulent N. meningitidis serogroup C ST-11 (cc11) strain was found. The city of Empoli had the highest attack-rate during the outbreak and also the highest meningococcal serogroup C carriage-prevalence due to the outbreak-strain. Multivariate analyses underlined a convergence of risk factors, which partially confirmed those observed among meningococcal outbreak-cases, and that should be considered in targeted immunization campaigns.

Interconnected clusters of invasive meningococcal disease due to Neisseria meningitidis serogroup C ST-11 (cc11), involving bisexuals and men who have sex with men, with discos and gay-venues hotspots of transmission, Tuscany, Italy, 2015 to 2016.

In 2015 an increased incidence of invasive meningococcal disease due to serogroup-C (MenC) occurred in Tuscany, Italy. This led the Regional Health Authority of Tuscany to implement a reactive immunisation campaign and to launch an epidemiological field investigation aiming to address targeted immunisation interventions. In 2011-14, 10 MenC cases had been reported compared with 62 cases in 2015-16. The case fatality rate was 21% (n = 13) and 51 cases (82.3%) were confirmed as C:P1.5-1,10-8:F3-6:ST-11(cc11). Overall, 17 clusters were recognised. Six discos and four gay-venues were found to have a role as transmission-hotspots, having been attended by 20 and 14 cases in the 10 days before symptoms onset. Ten and three cases occurred, respectively, among men who have sex with men (MSM) and bisexual individuals, who were involved in 11 clusters. In addition, heterosexual cases (n = 5) attending gay-venues were also found. Secondary cases were not identified. Molecular typing indicated close relationship with MenC clusters recently described among gay, bisexual and other MSM in Europe and the United States, suggesting a possible international spread of the serogroup-C-variant P1.5-1,10-8:F3-6:ST-11(cc11) in this population-group; however, epidemiological links were not identified. In December 2016, a targeted vaccination campaign involving discos and lesbian, gay, bisexual, and transgender (LGBT) associations was implemented. During 2017, 10 cases of MenC occurred, compared with 32 and 30 cases reported in 2015 and 2016 respectively, suggesting the effectiveness of the reactive and targeted immunisation programmes.

Antibiotic use varies substantially among adults: a cross-national study from five European Countries in the ARITMO project.

PURPOSE: To examine patterns of outpatient and community antibiotic use among adults in five European countries. METHODS: We used healthcare data of 28.8 million adults from six population-based ARITMO project databases to ascertain information on systemic antibiotic use in Denmark (2000-2008), the Netherlands (1999-2010), Italy (2000-2010), the UK (1996-2009), and Germany (2004-2008). We estimated overall, and age-group and sex specific antibiotic use as defined daily doses (DDD) per 1000 inhabitants per day. We computed annual age- and sex-standardized population prevalence of antibiotic use per 1000 persons-years (p-y) and the mean duration (in days) of antibiotic use. RESULTS: The overall antibiotic use varied from 8.7 DDD per 1000 inhabitants per day in the UK to 18.1 DDD in Denmark, representing a 2.1-fold geographical variation. In all countries, prescribing was relatively high among individuals aged 15-19 years; lower in those aged 20-50 years; and then increased steadily reaching 41.8 DDD per 1000 inhabitants per day in individuals ≥ 85 years in Denmark. After age- and sex-standardization, prevalence of antibiotic use varied threefold from 160.2/1000 p-y in the UK to 421.1/1000 p-y in Italy. The ratio of broad- to narrow-spectrum penicillin, cephalosporin, and macrolide use varied from 0.6 in Denmark to 120.2 in Italy. Women used more antibiotics than men did in all countries. Across countries, the mean duration of antibiotic use varied 1.3 to 21.1-fold for different antibiotics. CONCLUSIONS: Antibiotic use is high in women and the elderly. Prescribing patterns vary substantially across European countries, both according to overall consumption, user prevalence, duration, and narrow- versus broad-spectrum antibiotics.

Trends in paediatric macrolide use in five European countries-a population-based study.

PURPOSE: The study aims to analyse overall as well as subgroup-specific outpatient paediatric macrolide use in five European countries, including time trends of macrolide prescription rates, and to provide potential targets for future interventions aiming to promote judicious macrolide use. METHODS: Macrolide prescription rates per 1000 person years to paediatric outpatients (≤18 years) were calculated using healthcare databases from Denmark, Germany, Italy, The Netherlands and the UK. Poisson regression analysis was used to estimate the influence of increasing calendar year on total macrolide and subgroup-specific prescription rates based on monthly data, adjusted for seasonal variations. Time periods for which data were available varied between 4 (Italy 2007-10, Germany 2005-8) and 10 years (UK 2000-9). RESULTS: Paediatric macrolide use in 2008 varied between 199 (Italy) and 47 (Netherlands) prescriptions per 1000 person years. Prescription rates of short-acting macrolides declined significantly in all countries but the UK. The use of intermediate-acting macrolides significantly rose with increasing calendar year in Denmark (rate ratio (RR) = 1.12) and the UK (RR = 1.06), but decreased in Germany (RR = 0.84) and The Netherlands (RR = 0.97). Prescription rates of long-acting agents increased in Denmark (RR = 1.05), The Netherlands (RR = 1.05) and the UK (RR = 1.11) (all trends p < 0.05). The greatest seasonal variations of macrolide use between summer and winter months were observed in Italy and Germany. CONCLUSIONS: The observed trend toward increased prescribing of intermediate- and/or long-acting agents might further increase resistance pressure on bacterial pathogens due to their prolonged plasma half-life and broader antibacterial activity. Marked seasonality of prescription rates in the high-utilising countries, Italy and Germany, suggests frequent prescription of macrolides to treat respiratory infections which may be of viral origin.

Systemic antibiotic prescribing to paediatric outpatients in 5 European countries: a population-based cohort study.

BACKGROUND: To describe the utilisation of antibiotics in children and adolescents across 5 European countries based on the same drug utilisation measures and age groups. Special attention was given to age-group-specific distributions of antibiotic subgroups, since comparison in this regard between countries is lacking so far. METHODS: Outpatient paediatric prescriptions of systemic antibiotics during the years 2005-2008 were analysed using health care databases from the UK, the Netherlands, Denmark, Italy and Germany. Annual antibiotic prescription rates per 1,000 person years were estimated for each database and stratified by age (≤4, 5-9, 10-14, 15-18 years). Age-group-specific distributions of antibiotic subgroups were calculated for 2008. RESULTS: With 957 prescriptions per 1000 person years, the highest annual prescription rate in the year 2008 was found in the Italian region Emilia Romagna followed by Germany (561), the UK (555), Denmark (481) and the Netherlands (294). Seasonal peaks during winter months were most pronounced in countries with high utilisation. Age-group-specific use varied substantially between countries with regard to total prescribing and distributions of antibiotic subgroups. However, prescription rates were highest among children in the age group ≤4 years in all countries, predominantly due to high use of broad spectrum penicillins. CONCLUSIONS: Strong increases of antibiotic prescriptions in winter months in high utilising countries most likely result from frequent antibiotic treatment of mostly viral infections. This and strong variations of overall and age-group-specific distributions of antibiotic subgroups across countries, suggests that antibiotics are inappropriately used to a large extent.

The pathology of hype, hyperbole and publication bias is creating an unwarranted concern towards biodegradable mulch films.

The idea that it is a risk to promote biodegradable mulch films on a large scale is becoming established at academic level based on a series of articles similar in approach and conclusions. However, a critical analysis shows that the results do not justify the alarmist tones. The negative effects of hand-cut pieces of virgin material added in pots at concentrations up to 714 times the application doses are ascribed to the "accumulation" and "contamination" of "residues" and "debris" of biodegradable plastics. Yet, no accumulation and no contamination of biodegradable microplastics has actually been shown. No Predicted Environmental Concentration was established, thus the use of the term risk is inappropriate. The hypothesis of transient phytotoxicity of organic matter under decomposition i.e., an artificial outcome of the experimental scheme used, was not considered. A scrupulous approach to terminology is very important for the quality of communication and for the development of innovations. Scientific communication is a delicate process in which and to avoid hyperbole, there must be strict logical and lexical consistency between results and conclusions. Guidelines on the communication of the results of studies on biodegradable mulch must be developed to avoid the spread of unjustified concerns.

Rebuttal of the arguments put forward in the Letter to the Editor by Nizzetto et al.

In their Letter to the Editor, Nizzetto et al. challange a recent article in which I show that there has been unwarranted alarmism about biodegradable mulch films due to the publication of numerous articles based on preliminary data that are irrelevant for drawing conclusions on environmental risk. The tendency to over-emphasise results in order to attract attention is a growing problem in the scientific world and has been studied by many scholars. Nizzetto et al. accuse me of not using scientific methodology and of not disclosing that I am a scientist working for a company that produces biodegradable plastics. In this rebuttal I show that Nizzetto et al.'s accusations suffer from a number of logical fallacies, in particular the "straw man" fallacy and the "ad hominem" fallacy.

Monitoring biodegradation of poly(butylene sebacate) by Gel Permeation Chromatography, (1)H-NMR and (31)P-NMR techniques.

The increasing use of new generation plastics has been accompanied by the development of standard methods for studying their biodegradability. Generally, test methods are based on the measurement of CO(2) production, i.e. the mineralization degree of the tested materials. However, in order to describe the biodegradation process, the determination of the residual amount of tested material which remains in the environment and its chemical characterization can be very important. In this study, the biodegradation in soil of a model polyester (poly(butylene sebacate)) was monitored. Gel Permeation Chromatography and Nuclear Magnetic Resonance ((31)P-NMR and (1)H-NMR) were used in order to obtain information about the polyester structure and the possible by-products that can be found in soil during and at the end of the incubation. The polyester mineralization (i.e. the CO(2) production) was tested according to ASTM 5988 standard method for 245 days. When the polyester mineralization was about 21% and 37% (after 78 and 140 days of incubation) and at the end of the process (63% of mineralization, 100% if compared to the cellulose used as reference material), the soil was extracted with chloroform (solvent of the tested substance) and the extracts were analyzed using GPC and NMR acquisitions. The analytical acquisitions showed high molecular weight polyester in soil during the incubation (78 and 140 days): the polyester concentration decreased but its structure remained almost the same with a slow decreasing in molecular weight. At the end of the test (245 days) no film of the polyester could be extracted from the soil: NMR acquisitions and GPC analyses of the extracts suggested a strong degraded structure of the residual polyester. Even if at the end of the process only 63% of carbon had been lost by mineralization, the whole of the added polyester seems to have disappeared after about eight months of incubation, suggesting substantial biomass formation.

[Risk factors associated with road accidents among young people in Tuscany (Italy): a cross sectional study]. / Fattori di rischio associati agli incidenti stradali nei giovani toscani: uno studio trasversale.

In most countries, national statistics institutes either do not measure or underestimate the impact of behavioral aspects as causes of road accidents. To bridge this gap, the Regional Health Agency of Tuscany (Italy) created the EDIT project, which evaluates driving behaviors and other lifestyle risk factors in a sample of secondary school students. Study results show that driving while under the influence of alcohol or drugs or while being distracted by cigarette smoking or the use of mobile phones are the risk factors most frequently associated with traffic accidents.

Sample size calculation and optimal design for regression-based norming of tests and questionnaires.

To prevent mistakes in psychological assessment, the precision of test norms is important. This can be achieved by drawing a large normative sample and using regression-based norming. Based on that norming method, a procedure for sample size planning to make inference on Z-scores and percentile rank scores is proposed. Sampling variance formulas for these norm statistics are derived and used to obtain the optimal design, that is, the optimal predictor distribution, for the normative sample, thereby maximizing precision of estimation. This is done under five regression models with a quantitative and a categorical predictor, differing in whether they allow for interaction and nonlinearity. Efficient robust designs are given in case of uncertainty about the regression model. Furthermore, formulas are provided to compute the normative sample size such that individuals' positions relative to the derived norms can be assessed with prespecified power and precision. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hyperferritinemia and liver iron content determined with MRI: Reintroduction of the liver iron index.

BACKGROUND: Hyperferritinemia is found in around 12 % of the general population. Analyzing the cause can be difficult. In case of doubt about the presence of major iron overload most guidelines advice to perform a MRI as a reliable non-invasive marker to measure liver iron concentration (LIC). In general, a LIC of ≥ 36 µmol/g dw is considered the be elevated however in hyperferritinemia associated with, for example, obesity or alcohol (over)consumption the LIC can be ≥ 36 µmol/g dw in abscence of major iron overload. So, unfortunately a clear cut-off value to differentiate iron overload from normal iron content is lacking. Previously the liver iron index (LII) (LIC measured in liver biopsy (LIC-b)/age (years)), was introduced to differentiate between patients with major (LII ≥ 2) and minor or no iron overload (LII < 2). Based on the good correlation between the LIC-b and LIC determined with MRI (LIC-MRI), our goal was to investigate whether a LII_MRI ≥ 2 is a good indicator of major iron overload, reflected by a significantly higher amount of iron needed to be mobilized to reach iron depletion. METHODS: We compared the amount of mobilized iron to reach depletion and inflammation-related characteristics in two groups: LII-MRI ≥ 2 versus LII-MRI <2 in 92 hyperferritinemia patients who underwent HFE genotyping and MRI-LIC determination. RESULTS: Significantly more iron needed to be mobilized to reach iron depletion in the LII ≥ 2 group (mean 4741, SD ± 4135 mg) versus the LII-MRI <2 group (mean 1340, SD ± 533 mg), P < 0.001. Furthermore, hyperferritinemia in LII-MRI < 2 patients was more often related to components of the metabolic syndrome while hyperferritinemia in LII-MRI ≥ 2 patients was more often related to HFE mutations. ROC curve analysis showed good performance of LII =2 as cut-off value. However the calculations showed that the optimal cut-off for the LII = 3.4. CONCLUSION: The LII-MRI with a cut-off value of 2 is an effective method to differentiate major from minor iron overload in patients with hyperferritinemia. But the LII-MRI = 3.4 seems a more promising diagnostic test for major iron overload.

Using electronic health care records for drug safety signal detection: a comparative evaluation of statistical methods.

BACKGROUND: Drug safety monitoring relies primarily on spontaneous reporting, but electronic health care record databases offer a possible alternative for the detection of adverse drug reactions (ADRs). OBJECTIVES: To evaluate the relative performance of different statistical methods for detecting drug-adverse event associations in electronic health care record data representing potential ADRs. RESEARCH DESIGN: Data from 7 databases across 3 countries in Europe comprising over 20 million subjects were used to compute the relative risk estimates for drug-event pairs using 10 different methods, including those developed for spontaneous reporting systems, cohort methods such as the longitudinal gamma poisson shrinker, and case-based methods such as case-control. The newly developed method "longitudinal evaluation of observational profiles of adverse events related to drugs" (LEOPARD) was used to remove associations likely caused by protopathic bias. Data from the different databases were combined by pooling of data, and by meta-analysis for random effects. A reference standard of known ADRs and negative controls was created to evaluate the performance of the method. MEASURES: The area under the curve of the receiver operator characteristic curve was calculated for each method, both with and without LEOPARD filtering. RESULTS: The highest area under the curve (0.83) was achieved by the combination of either longitudinal gamma poisson shrinker or case-control with LEOPARD filtering, but the performance between methods differed little. LEOPARD increased the overall performance, but flagged several known ADRs as caused by protopathic bias. CONCLUSIONS: Combinations of methods demonstrate good performance in distinguishing known ADRs from negative controls, and we assume that these could also be used to detect new drug safety signals.

Kinetics of monomer biodegradation in soil.

In modern intensive agriculture, plastics are used in several applications (i.e. mulch films, drip irrigation tubes, string, clips, pots, etc.). Interest towards applying biodegradable plastics to replace the conventional plastics is promising. Ten monomers, which can be applied in the synthesis of potentially biodegradable polyesters, were tested according to ASTM 5988-96 (standard respirometric test to evaluate aerobic biodegradation in soil by measuring the carbon dioxide evolution): adipic acid, azelaic acid, 1,4-butanediol, 1,2-ethanediol, 1,6-hexanediol, lactic acid, glucose, sebacic acid, succinic acid and terephthalic acid. Eight replicates were carried out for each monomer for 27-45 days. The numerical code AQUASIM was applied to process the CO2 experimental data in order to estimate values for the parameters describing the different mechanisms occurring to the monomers in soil: i) the first order solubilization kinetic constant, K(sol) (d⁻¹); ii) the first order biodegradation kinetic constant, K(b) (d⁻¹); iii) the lag time in biodegradation, t(lag) (d); and iv) the carbon fraction biodegraded but not transformed into CO2, Y (-). The following range of values were obtained: [0.006 d⁻¹, 6.9 d⁻¹] for K(sol), [0.1 d⁻¹, 1.2 d⁻¹] for K(b), and [0.32-0.58] for Y; t(lag) was observed for azelaic acid, 1,2-ethanediol, and terephthalic acid, with estimated values between 3.0 e 4.9 d.