A. Mayo

Incidence, organ dysfunction and mortality in severe sepsis: a Spanish multicentre study

IntroductionSepsis is a leading cause of admission to non-cardiological intensive care units (ICUs) and the second leading cause of death among ICU patients. We present the first extensive dataset on the epidemiology of severe sepsis treated in ICUs in Spain.MethodsWe conducted a prospective, observational, multicentre cohort study, carried out over two 3-month periods in 2002. Our aims were to determine the incidence of severe sepsis among adults in ICUs in a specific area in Spain, to determine the early (48 h) ICU and hospital mortality rates, as well as factors associated with the risk of death.ResultsA total of 4,317 patients were admitted and 2,619 patients were eligible for the study; 311 (11.9%) of these presented at least 1 episode of severe sepsis, and 324 (12.4%) episodes of severe sepsis were recorded. The estimated accumulated incidence for the population was 25 cases of severe sepsis attended in ICUs per 100,000 inhabitants per year. The mean logistic organ dysfunction system (LODS) upon admission was 6.3; the mean sepsis-related organ failure assessment (SOFA) score on the first day was 9.6. Two or more organ failures were present at diagnosis in 78.1% of the patients. A microbiological diagnosis of the infection was reached in 209 episodes of sepsis (64.5%) and the most common clinical diagnosis was pneumonia (42.8%). A total of 169 patients (54.3%) died in hospital, 150 (48.2%) of these in the ICU. The mortality in the first 48 h was 14.8%. Factors associated with early death were haematological failure and liver failure at diagnosis, acquisition of the infection prior to ICU admission, and total LODS score on admission. Factors associated with death in the hospital were age, chronic alcohol abuse, increased McCabe score, higher LODS on admission, ΔSOFA 3-1 (defined as the difference in the total SOFA scores on day 3 and on day 1), and the difference of the area under the curve of the SOFA score throughout the first 15 days.ConclusionsWe found a high incidence of severe sepsis attended in the ICU and high ICU and hospital mortality rates. The high prevalence of multiple organ failure at diagnosis and the high mortality in the first 48 h suggests delays in diagnosis, in initial resuscitation, and/or in initiating appropriate antibiotic treatment.

Retinal image analysis based on mixture models to detect hard exudates.

Diabetic Retinopathy is one of the leading causes of blindness in developed countries. Hard exudates have been found to be one of the most prevalent earliest clinical signs of retinopathy. Thus, automatic detection of hard exudates from retinal images is clinically significant. In this study, an automatic method to detect hard exudates is proposed. The algorithm is based on mixture models to dynamically threshold the images in order to separate exudates from background. A postprocessing technique, based on edge detection, is applied to distinguish hard exudates from cotton wool spots and other artefacts. We prospectively assessed the algorithm performance using a database of 80 retinal images with variable colour, brightness, and quality. The algorithm obtained a sensitivity of 90.2% and a positive predictive value of 96.8% using a lesion-based criterion. The image-based classification accuracy is also evaluated obtaining a sensitivity of 100% and a specificity of 90%.

Prevalence of primary open-angle glaucoma in a Spanish population: the Segovia study.

PurposeTo determine the prevalence of primary open-angle glaucoma (POAG) in Segovia, Spain. MethodsWe conducted a cross-sectional, population-based epidemiologic study, the target population of which was residents of Segovia, Spain, aged 40 to 79 years. A sample of 569 subjects was randomly selected in a stratified manner according to gender and age groups. All participants underwent a complete ophthalmic examination that included measurement of visual acuity and refraction, tonometry, anterior segment biomicroscopy, funduscopy, stereoscopic photographs of the optic nerve head, and automated white-on-white visual field testing. Two independent observers evaluated the optic nerve photographs and visual fields. The diagnosis of POAG was established when any eye had an open angle and a glaucomatous optic nerve and glaucomatous visual field. The prevalence of POAG in the population was estimated from the prevalence in the complete sample and the patients already diagnosed at the only glaucoma service in the city. ResultsThe estimated prevalences (99% confidence interval) in the population were, respectively, 2.1% (1.9–2.3%), and 1.7% (1.6–1.8%) for POAG and ocular hypertension. The prevalence of POAG increased with age (P < 0.005) and tended to be greater (P = 0.054) in men (2.4%) than women (1.7%). ConclusionThe prevalence of POAG in this Segovia population is 2.1%, similar to that estimated in previous studies performed in predominantly Caucasian populations.

Ocular Mucin Gene Expression Levels as Biomarkers for the Diagnosis of Dry Eye Syndrome

PURPOSE To evaluate mRNA levels of the ocular mucins MUC1, MUC2, MUC4, MUC5AC, and MUC7 in conjunctival impression cytology samples from patients with moderate to severe dry eye syndrome (DES) compared with a population of healthy subjects; and to investigate the use of the levels of these mucin genes as biomarkers of DES and subsequently as a potential diagnostic test for DES. METHODS This prospective study commenced in the year 2000 and ended in the year 2009. Thirty-eight patients with DES and 43 age- and sex-matched healthy subjects completed the initial part of the study. Investigations were repeated at a later stage in 16 healthy subjects and 30 patients with DES, which were used as external validation data. Conjunctival impression cytology was performed in all subjects to test gene expression of ocular mucin genes MUC1, MUC2, MUC4, MUC5AC, and MUC7. Statistical analysis was performed to determine whether there was a difference in the levels of mucin gene expression between the two groups of subjects. Sensitivity and specificity of mucin gene expression for the diagnosis of DES was calculated. RESULTS Expressions of MUC1, MUC2, MUC4, and MUC5AC (P < 0.0001) were significantly lower in conjunctival epithelium of patients with DES compared with that in normal subjects. These results were replicated in the external control subject and patient groups. MUC1 expression levels demonstrated the greatest sensitivity (83.3%) and specificity (87.5%) among all genes tested. CONCLUSIONS The data strongly suggest that the expression levels of MUC1 may be used as a diagnostic test in DES for investigational and selective clinical trials.

Mixture Model-based Clustering and Logistic Regression for Automatic Detection of Microaneurysms in Retinal Images

Diabetic Retinopathy is one of the leading causes of blindness and vision defects in developed countries. An early detection and diagnosis is crucial to avoid visual complication. Microaneurysms are the first ocular signs of the presence of this ocular disease. Their detection is of paramount importance for the development of a computer-aided diagnosis technique which permits a prompt diagnosis of the disease. However, the detection of microaneurysms in retinal images is a difficult task due to the wide variability that these images usually present in screening programs. We propose a statistical approach based on mixture model-based clustering and logistic regression which is robust to the changes in the appearance of retinal fundus images. The method is evaluated on the public database proposed by the Retinal Online Challenge in order to obtain an objective performance measure and to allow a comparative study with other proposed algorithms.

Epidemiology of Refractive Errors in an Adult European Population: The Segovia Study

ABSTRACT Purpose: To determine the prevalence of refractive errors in Segovia, Spain. Methods: A cohort of 569 subjects was randomly selected in a stratified manner according to gender and age in a cross-sectional, population-based epidemiologic study, the target population of which was urban residents aged 40 to 79 years. All participants underwent an ophthalmic examination that included measurement of visual acuity (VA) and refraction, tonometry, anterior segment biomicroscopy, funduscopy, optic nerve head photography, and visual field testing. Of those, 417 subjects were enrolled who met the inclusion criteria of a phakic right eye and VA over 20/40. The prevalence of spherical errors was assessed after calculating the spherical equivalent and defining myopia as −0.5 diopters (D) or less and hyperopia as +0.50 D or more. The prevalence of astigmatism over 0.50 D was evaluated in minus cylinder form. Results: The estimated prevalences (95% confidence interval) of myopia, hyperopia, and astigmatism, in the population were 25.4% (21.5–29.8%) 43.6% (39–48.4%), and 53.5% (48.7–58.2%), respectively. No significant gender difference was found in the prevalence of any refractive errors. The prevalence of myopia or the mean value did not change significantly with age. The mean hyperopia and the mean astigmatism (p < 0.01 for both) and the prevalence increased with increasing age (p < 0.01 for both). Anisometropia of 1 D or more was present in 12.3% (49/396 subjects). Conclusion: More than 60% of the Segovia population over 40 years of age has a refractive error, with 25.4% myopic and 43.6% hyperopic. Astigmatism is present in over half of the population and the types change with age.

Levels of mucin gene expression in normal human conjunctival epithelium in vivo

Purpose. Conjunctival impression cytology (CIC) samples were used to determine the mean and normal range of mRNA levels of human MUC1, MUC2, MUC4, MUC5AC, and MUC7 mucin genes. Methods. Real time PCR was performed to determine normal mRNA levels in CIC samples of 24 male and 19 female healthy donors. Correlation coefficients between gene expression levels were obtained. Results. All five mucin genes were expressed in the CIC samples. MUC1 and MUC4 were present at the highest level and MUC2 was at the lowest. There were no gender differences. Significant positive correlations existed between MUC2 and MUC4 and between MUC2 and MUC7 levels. Conclusions. Normal levels and ranges of mRNAs for MUC1, MUC2, MUC4, MUC5AC and MUC7 conjunctival mucin genes have been established for the first time. These data may serve as the normal threshold values for future comparisons in different experimental and pathological conditions involving the ocular surface.

Quantitative magnetoencephalography of spontaneous brain activity in Alzheimer disease : An exhaustive frequency analysis

Quantitative magnetoencephalography (qMEG) was used to investigate differences in the 2 to 60 Hz spectral power, between Alzheimer disease (AD) patients and control subjects. Twenty-two AD patients and 21 age-matched control subjects participated in this study. MEG signal analysis comprised the division of the entire 2 to 60 Hz spectrum in 2 Hz-width subbands. Both the relative power and the contribution of each subband to the correct classification of AD patients and controls were calculated. The relative power in 2 bands comprised between 2 to 4 Hz and 16 to 28 Hz was selected by a restrictive multiple-comparison test, among the entire 2 to 60 Hz spectrum. Using 2 to 4 Hz values it is possible to choose a classification rule with an estimate sensitivity and specificity given by 68% and 76% respectively. Alternatively, when 16 to 28 Hz values are used, it is possible to obtain a better classification rule with an estimate sensitivity and specificity given by 81% and 80%, respectively. To the best of our knowledge, this is the first electroencephalography or MEG study where a so exhaustive analysis of the magneto-electric spectrum has been performed. This study supports the notion that more attention should be devoted to the study of β band in AD.

Automatic Image Processing Algorithm to Detect Hard Exudates based on Mixture Models

Automatic detection of hard exudates from retinal images is clinically significant. Hard exudates are associated with diabetic retinopathy and have been found to be one of the most prevalent earliest clinical signs of retinopathy. In this study, an automatic method to detect hard exudates is proposed. The algorithm is based on mixture models to dynamically threshold the images in order to separate hard exudates from background. We prospectively assessed the algorithm performance using a database of 20 retinal images with variable color, brightness, and quality. The algorithm obtained a sensitivity of 90.23% and a predictive value of 82.5% using a lesion-based criterion. The image-based classification accuracy is also evaluated obtaining a sensitivity of 100% and a specificity of 90%

Conjunctival mucin mRNA expression in contact lens wear.

Purpose. To investigate the influence of the water content in non-ionic hydrogel contact lenses (HCL) on the mRNA levels of human conjunctival mucin genes (MUCs). Methods. Sixteen healthy subjects with no history of contact lenses wear were selected and randomized into two equal groups. Group 1 subjects wore low water content (38%, Soflens 38) non-ionic HCLs. Group 2 wore high water content (66%, Soflens 66) non-ionic HCLs. Conjunctival impression cytology was applied to the superior bulbar conjunctiva of both eyes before, 6 months, and 1 year after HCL fitting, and 15 days after discontinuation of wearing. Total RNA was isolated, retrotranscribed, and amplified by conventional polymerase chain reaction (PCR) and by quantitative real time PCR to study the mRNA levels of MUCs and to analyze variations during the study period. Time- and HCL-dependent variations in mRNA expression were analyzed using Student’s test. Results. From the known MUCs, transcripts from MUC1, MUC2, MUC4, MUC5AC, MUC7, MUC13, MUC15, MUC16, and MUC17 genes were detected in all subjects before HCL fitting. Except for MUC2, the expression of some MUC genes significantly increased whereas others significantly decreased at either the 6- and 12-month period. Statistically significant differences between both HCL groups (p < 0.001) were found in the MUC4, MUC13, and MUC15 mRNA expression after 1 year of wear and after the 15 days without HCL wear. However, these differences were not clearly related to the water content of the lenses. Conclusions. Low and high water content non-ionic HCLs induced different changes in the mRNA levels of several MUCs, but the water content was not related to the changes. Recovery to basal levels of conjunctival MUC mRNA expression after wearing HCL lenses for a year takes longer than 15 days for some MUCs.