Predicting chronic kidney disease progression with artificial intelligence.

BACKGROUND: The use of tools that allow estimation of the probability of progression of chronic kidney disease (CKD) to advanced stages has not yet achieved significant practical importance in clinical setting. This study aimed to develop and validate a machine learning-based model for predicting the need for renal replacement therapy (RRT) and disease progression for patients with stage 3-5 CKD. METHODS: This was a retrospective, closed cohort, observational study. Patients with CKD affiliated with a private insurer with five-year follow-up data were selected. Demographic, clinical, and laboratory variables were included, and the models were developed based on machine learning methods. The outcomes were CKD progression, a significant decrease in the estimated glomerular filtration rate (eGFR), and the need for RRT. RESULTS: Three prediction models were developed-Model 1 (risk at 4.5 years, n = 1446) with a F1 of 0.82, 0.53, and 0.55 for RRT, stage progression, and reduction in the eGFR, respectively,- Model 2 (time- to-event, n = 2143) with a C-index of 0.89, 0.67, and 0.67 for RRT, stage progression, reduction in the eGFR, respectively, and Model 3 (reduced Model 2) with C-index = 0.68, 0.68 and 0.88, for RRT, stage progression, reduction in the eGFR, respectively. CONCLUSION: The time-to-event model performed well in predicting the three outcomes of CKD progression at five years. This model can be useful for predicting the onset and time of occurrence of the outcomes of interest in the population with established CKD.

Diagnostic yield of chromosomal microarray in the largest Latino clinical cohort.

Copy number variants (CNVs) remain a major etiological cause of neurodevelopmental delay and congenital malformations. Chromosomal microarray analysis (CMA) represents the gold standard for CNVs molecular characterization. We applied CMA throughout the patient's clinical diagnostic workup, as the patient's medical provider requested. We collected CMA results of 3380 patients enrolled for 5 years (2016-2021). We found 830 CNVs in 719 patients with potential clinical significance, that is, (i) pathogenic, (ii) likely pathogenic, and (iii) variants of uncertain significance (VUS), from which 10.6% (predominantly involving chromosomes 15 and 22) were most likely the final cause underpinning the patients' clinical phenotype. For those associated with neurodevelopmental phenotypes, the rate of pathogenic or likely pathogenic findings among the patients with CNVs was 60.75%. When considering epileptic phenotypes, it was 59%. Interestingly, our protocol identified two gains harbored in 17q21.31 and 9q34.3, internationally classified initially as VUS. However, because of their high frequency, we propose that these two VUS be reclassified as likely benign in this widely heterogeneous phenotypic population. These results support the diagnostic yield efficiency of CMA in characterizing CNVs to define the final molecular cause of genetic diseases in this cohort of Colombian patients, the most significant sample of patients from a Latino population, and define new benign polymorphic CNVs.

Host Transcriptional Regulatory Genes and Microbiome Networks Crosstalk through Immune Receptors Establishing Normal and Tumor Multiomics Metafirm of the Oral-Gut-Lung Axis.

The microbiome has shown a correlation with the diet and lifestyle of each population in health and disease, the ability to communicate at the cellular level with the host through innate and adaptative immune receptors, and therefore an important role in modulating inflammatory process related to the establishment and progression of cancer. The oral cavity is one of the most important interaction windows between the human body and the environment, allowing the entry of an important number of microorganisms and their passage across the gastrointestinal tract and lungs. In this review, the contribution of the microbiome network to the establishment of systemic diseases like cancer is analyzed through their synergistic interactions and bidirectional crosstalk in the oral-gut-lung axis as well as its communication with the host cells. Moreover, the impact of the characteristic microbiota of each population in the formation of the multiomics molecular metafirm of the oral-gut-lung axis is also analyzed through state-of-the-art sequencing techniques, which allow a global study of the molecular processes involved of the flow of the microbiota environmental signals through cancer-related cells and its relationship with the establishment of the transcription factor network responsible for the control of regulatory processes involved with tumorigenesis.

Multiclass classification of breast cancer histopathology images using multilevel features of deep convolutional neural network.

Breast cancer is a common malignancy and a leading cause of cancer-related deaths in women worldwide. Its early diagnosis can significantly reduce the morbidity and mortality rates in women. To this end, histopathological diagnosis is usually followed as the gold standard approach. However, this process is tedious, labor-intensive, and may be subject to inter-reader variability. Accordingly, an automatic diagnostic system can assist to improve the quality of diagnosis. This paper presents a deep learning approach to automatically classify hematoxylin-eosin-stained breast cancer microscopy images into normal tissue, benign lesion, in situ carcinoma, and invasive carcinoma using our collected dataset. Our proposed model exploited six intermediate layers of the Xception (Extreme Inception) network to retrieve robust and abstract features from input images. First, we optimized the proposed model on the original (unnormalized) dataset using 5-fold cross-validation. Then, we investigated its performance on four normalized datasets resulting from Reinhard, Ruifrok, Macenko, and Vahadane stain normalization. For original images, our proposed framework yielded an accuracy of 98% along with a kappa score of 0.969. Also, it achieved an average AUC-ROC score of 0.998 as well as a mean AUC-PR value of 0.995. Specifically, for in situ carcinoma and invasive carcinoma, it offered sensitivity of 96% and 99%, respectively. For normalized images, the proposed architecture performed better for Makenko normalization compared to the other three techniques. In this case, the proposed model achieved an accuracy of 97.79% together with a kappa score of 0.965. Also, it attained an average AUC-ROC score of 0.997 and a mean AUC-PR value of 0.991. Especially, for in situ carcinoma and invasive carcinoma, it offered sensitivity of 96% and 99%, respectively. These results demonstrate that our proposed model outperformed the baseline AlexNet as well as state-of-the-art VGG16, VGG19, Inception-v3, and Xception models with their default settings. Furthermore, it can be inferred that although stain normalization techniques offered competitive performance, they could not surpass the results of the original dataset.

Structural Protein Effects Underpinning Cognitive Developmental Delay of the PURA p.Phe233del Mutation Modelled by Artificial Intelligence and the Hybrid Quantum Mechanics-Molecular Mechanics Framework.

A whole-exome capture and next-generation sequencing was applied to an 11 y/o patient with a clinical history of congenital hypotonia, generalized motor and cognitive neurodevelopmental delay, and severe cognitive deficit, and without any identifiable Syndromic pattern, and to her parents, we disclosed a de novo heterozygous pathogenic mutation, c.697_699del p.Phe233del (rs786204835)(ACMG classification PS2, PM1, PM2, PP5), harbored in the PURA gene (MIM*600473) (5q31.3), associated with Autosomal Dominant Mental Retardation 31 (MIM # 616158). We used the significant improvement in the accuracy of protein structure prediction recently implemented in AlphaFold that incorporates novel neural network architectures and training procedures based on the evolutionary, physical, and geometric constraints of protein structures. The wild-type (WT) sequence and the mutated sequence, missing the Phe233, were reconstructed. The predicted local Distance Difference Test (lDDT) for the PURAwt and the PURA-Phe233del showed that the occurrence of the Phe233del affects between 220-320 amino acids. The distortion in the PURA structural conformation in the ~5 Å surrounding area after the p.Phe233del produces a conspicuous disruption of the repeat III, where the DNA and RNA helix unwinding capability occurs. PURA Protein-DNA docking corroborated these results in an in silico analysis that showed a loss of the contact of the PURA-Phe233del III repeat domain model with the DNA. Together, (i) the energetic and stereochemical, (ii) the hydropathic indexes and polarity surfaces, and (iii) the hybrid Quantum Mechanics-Molecular Mechanics (QM-MM) analyses of the PURA molecular models demarcate, at the atomic resolution, the specific surrounding region affected by these mutations and pave the way for future cell-based functional analysis. To the best of our knowledge, this is the first report of a de novo mutation underpinning a PURA syndrome in a Latin American patient and highlights the importance of predicting the molecular effects in protein structure using artificial intelligence algorithms and molecular and atomic resolution stereochemical analyses.

Ataxia with Ocular Apraxia Type 1 (AOA1) (APTX, W279* Mutation): Neurological, Neuropsychological, and Molecular Outlining of a Heterogenous Phenotype in Four Colombian Siblings.

Hereditary ataxias are a group of devastating neurological disorders that affect coordination of gait and are often associated with poor coordination of hands, speech, and eye movements. Ataxia with ocular apraxia type 1 (AOA1) (OMIM: 606,350.0006) is characterized by slowly progressive symptoms of childhood-onset and pathogenic mutations in APTX; the only known cause underpinning AOA1. APTX encodes the protein aprataxin, composed of three domains sharing homology with proteins involved in DNA damage, signaling, and repair. We present four siblings from an endogamic family in a rural, isolated town of Colombia with ataxia and ocular apraxia of childhood-onset and confirmed molecular diagnosis of AOA1, homozygous for the W279* p.Trp279Ter mutation. We predicted the mutated APTX with AlphaFold to demonstrate the effects of this stop-gain mutation that deletes three beta helices encoded by amino acid 270 to 339 rescinding the C2H2-type zinc fingers (Znf) (C2H2 Znf) DNA-binding, the DNA-repair domain, and the whole 3D structure of APTX. All siblings exhibited different ages of onset (4, 6, 8, and 11 years old) and heterogeneous patterns of dysarthria (ranging from absence to mild-moderate dysarthria). Neuropsychological evaluation showed no neurocognitive impairment in three siblings, but one sibling showed temporospatial disorientation, semantic and phonologic fluency impairment, episodic memory affection, constructional apraxia, moderate anomia, low executive function, and symptoms of depression. To our knowledge, this report represents the most extensive series of siblings affected with AOA1 in Latin America, and the genetic analysis completed adds important knowledge to outline this family's disease and general complex phenotype of hereditary ataxias.

A Comprehensive Machine Learning Framework for the Exact Prediction of the Age of Onset in Familial and Sporadic Alzheimer's Disease.

Machine learning (ML) algorithms are widely used to develop predictive frameworks. Accurate prediction of Alzheimer's disease (AD) age of onset (ADAOO) is crucial to investigate potential treatments, follow-up, and therapeutic interventions. Although genetic and non-genetic factors affecting ADAOO were elucidated by other research groups and ours, the comprehensive and sequential application of ML to provide an exact estimation of the actual ADAOO, instead of a high-confidence-interval ADAOO that may fall, remains to be explored. Here, we assessed the performance of ML algorithms for predicting ADAOO using two AD cohorts with early-onset familial AD and with late-onset sporadic AD, combining genetic and demographic variables. Performance of ML algorithms was assessed using the root mean squared error (RMSE), the R-squared (R2), and the mean absolute error (MAE) with a 10-fold cross-validation procedure. For predicting ADAOO in familial AD, boosting-based ML algorithms performed the best. In the sporadic cohort, boosting-based ML algorithms performed best in the training data set, while regularization methods best performed for unseen data. ML algorithms represent a feasible alternative to accurately predict ADAOO with little human intervention. Future studies may include predicting the speed of cognitive decline in our cohorts using ML.

Determinants of adherence to continuous positive airway pressure therapy in adults with obstructive sleep apnea / Determinantes de adherencia a presión positiva continua de la via aérea en adultos con apnea del sueño

ASBTRACT Objectives Adherence to continuous positive airway pressure (CPAP) devices in patients with obstructive sleep apnea (OSA) determines the effectiveness of the treat-ment. Likewise, the assessment of the control of the disease must consider the information referred by the patient, among other value-based health measures related to the satisfaction of the intervention. The objectives of this study were a) Determine the factors related to adherence to CPAP devices in subjects with OSA affiliated to an insurance company of the healthcare system in Colombia. b) Assess symptom control associated to the disease from the individual's perspective and his/her satisfaction with the treatment received. Materials and Methods 1,501 subjects with OSA were surveyed by telephone to explore: sociodemographic factors, habits and lifestyles, use of CPAP and its adverse events, control of the disease, comorbidities, access to care and therapy satisfaction. Using multilevel logistic regression techniques, the influence of the various factors on adherence to CPAP was analyzed, using Stata 13 software. Results Adherence to CPAP therapy was of 58% and the control of symptoms was of 41.7%. The factors that determined the use of CPAP were knowledge on how the device operates, and the disturbances during sleep due to the mask or nasal pad. The-rapy satisfaction was predominantly very good or good. Conclusion Even with moderate adherence values and a good experience with CPAP therapy, symptomatic control of the disease is poor. Many of the factors that affect the use of CPAP are modifiable with a proper approach by the devices' service provider.

RESUMEN Objetivos La adherencia a los dispositivos de presión positiva continua de la vía aérea (CPAP) en pacientes con síndrome de apnea obstructiva del sueño (SAOS) define la efectividad del tratamiento. Los objetivos de este estudio fueron: a) Determinar los factores relacionados con la adherencia al CPAP en pacientes con SAOS de una aseguradora del Sistema General de Seguridad Social en Salud colombiano y b) evaluar el control de los síntomas de la enfermedad desde la perspectiva del individuo y su satisfacción con la terapia. Materiales y Métodos Mediante encuesta telefónica a 1 501 pacientes con SAOS se exploraron factores sociodemográficos, hábitos y estilos de vida, uso del CPAP y eventos adversos relacionados, control de la enfermedad, comorbilidad, acceso a la atención y satisfacción con la terapia. Utilizando técnicas de regresión logística mul-tinivel, se analizó la influencia de los distintos factores sobre la adherencia al CPAP mediante el software Stata 13. Resultados La adherencia al CPAP fue del 58% y el control de los síntomas del 41,7%. Los factores que determinaron el uso del CPAP fueron el conocimiento del funcionamiento del equipo y la dificultad para dormir debida a la mascarilla o la almohadilla nasal. La satisfacción con la terapia fue buena o muy buena predominantemente. Conclusiones Aún con valores de adherencia moderados y una buena experiencia con la terapia CPAP, el control sintomático de la enfermedad es pobre, pues varios de los factores afectan el uso del CPAP. Dichos factores se pueden intervenir con un adecuado abordaje por parte del prestador de servicios del dispositivo.

Recomendaciones para el uso racional de la prueba 25-hidroxivitamina D Resumen de política

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The exponential increase in the request for laboratory tests of 25-Hydroxyvitamin D or [25 (OH) D has ignited the alarms and generated a strong call for attention, since it may reflect deficiencies in the standardization of clinical practice and in the use non-systematic scientific evidence for decision-making in real life, which allows to analyze the indications of the test, its frequency, interpretation and even to assess the impact for health systems, especially when contrasted with the minimum or almost. No effects of the strategy of screening or supplying indiscriminately to the general population, without considering a comprehensive clinical assessment of risks and needs of people. From a purely public health impact point of view, the consequence of massive and unspecified requests is affecting most of the health systems and institutions at the global level. The primary studies that determined average population intake values have been widely used in the formulation of recommendations in Clinical Practice Guidelines, but unfortunately misinterpreted as cut points to diagnose disease and allow the exaggerated prescription of nutritional substitution. The coefficient of variation in routine tests to measure blood levels of 25 (OH) D is high (28%), decreasing the overall accuracy of the test and simultaneously, increasing both the falsely high and falsely low values. The most recent scientific evidence analyzes and seriously questions the usefulness and the real effect of the massive and indiscriminate practice of prescribing vitamin D without an exhaustive risk analysis. The available evidence is insufficient to recommend a general substitution of vitamin D to prevent fractures, falls, changes in bone mineral density, incidence of cardiovascular diseases, cerebrovascular disease, neoplasms and also to modify the growth curve of mothers' children. They received vitamin D as a substitute during pregnancy. The recommendations presented in the document are based on the critical analysis of current evidence and the principles of good clinical practice and invite to consider a rational use of 25 (OH) D tests in the context of a clinical practice focused on people and a comprehensive assessment of needs and risks. The principles of good practice suggest that clinicians may be able to justify that the results of the 25 (OH) D test strongly influence and define clinical practice and modify the outcomes that interest people and impact their health and wellness. Currently there is no clarity on how to interpret the results, and the relationship between symptoms and 25 (OH) D levels, which may not be consistent with the high prevalence of vitamin D deficiency reported. For this reason, it is suggested to review the rationale of the request for tests for systematic monitoring of levels of 25 (OH) D or in all cases where substitution is performed. Consider the use of 25 (OH) D tests within the comprehensive evaluation of people with suspicion or confirmation of the following conditions: rickets, osteomalacia, osteoporosis, hyper or hypoparathyroidism, malabsorption syndromes, sarcopenia, metabolic bone disease.

The cost of hospital care for HIV patients in Colombia: an insurer's perspective.

The aim of this study was to evaluate the cost derived from the hospitalization of people living with HIV (PLHIV) in Colombia between 2011 and 2015. This is an analysis of the direct cost of PLHIV hospitalization from the perspective of an insurer of the Colombian General Social Security System. The costs were calculated in Colombian pesos and corrected for inflation on the basis of the 2017 Consumer Price Index of the Bank of the Republic of Colombia. It was converted to US dollars at the Market Representative Exchange Rate of the same year. We analyzed 1129 hospitalizations in 612 PLHIV, of which 12% started with a diagnosis of HIV during the same hospitalization, with the majority in the AIDS stage (63%). The median overall cost of hospitalizations was US$1509 (25th and 75th percentiles: US$711-US$3254), being even higher in patients with AIDS and as the CD4 T lymphocyte count decreased. The cost derived from the medical care of PLHIV increases as the clinical control of the disease worsens, and it is a key indicator of the impact of the strategies implemented for the timely identification of the infection and subsequent management of the disease.

Generation of one iPSC line (IMEDEAi006-A) from an early-onset familial Alzheimer's Disease (fAD) patient carrying the E280A mutation in the PSEN1 gene.

The mutation E280A in PSEN1 (presenilin-1) is the most common cause of early-onset familial Alzheimer's Disease (fAD). It presents autosomal dominant inheritance and frequently leads to the manifestation of the disease in relatively young individuals. Here we report the generation of one PSEN1 E280A iPSC line derived from an early-onset patient. OriP/EBNA1-based episomal plasmids containing OCT3/4, SOX2, KLF4, L-MYC, LIN28, BCL-xL and shp53 were used to reprogram oral mucosa fibroblasts. The iPSC line generated has normal karyotype, carry the E280A mutation, is free of plasmid integration, express high levels of pluripotency markers and can differentiate into all three germ layers.

Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic Variants in Familial Alzheimer's Disease.

The identification of novel genetic variants contributing to the widespread in the age of onset (AOO) of Alzheimer's disease (AD) could aid in the prognosis and/or development of new therapeutic strategies focused on early interventions. We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia, Colombia. These individuals belong to the world largest multigenerational and extended pedigree segregating AD as a consequence of a dominant fully penetrant mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the late 1970s. To shed light on the genetic underpinning that could explain the large spread of the age of onset (AOO) of AD, 64 single nucleotide polymorphisms (SNP) associated with neuroanatomical, cardiovascular, and cognitive measures in AD were genotyped. Standard quality control and filtering procedures were applied, and single- and multi-locus linear mixed-effects models were used to identify AOO-associated SNPs. A full two-locus interaction model was fitted to define how identified SNPs interact to modulate AOO. We identified two key epistatic interactions between the APOE*E2 allele and SNPs ASTN2-rs7852878 and SNTG1-rs16914781 that delay AOO by up to ~ 8 years (95% CI 3.2-12.7, P = 1.83 × 10-3) and ~ 7.6 years (95% CI 3.3-11.8, P = 8.69 × 10-4), respectively, and validated our previous finding indicating that APOE*E2 delays AOO of AD in PSEN1 E280 mutation carriers. This new evidence involving APOE*E2 as an AOO delayer could be used for developing precision medicine approaches and predictive genomics models to potentially determine AOO in individuals genetically predisposed to AD.

Hemoglobinopathy detection through an institutional neonatal screening program in Colombia / Detecção de hemoglobinopatias por meio de um programa institucional de triagem neonatal na Colômbia

ABSTRACT Introduction: Hemoglobinopathies are among the most common genetic disorders of hemoglobin worldwide and a public health problem. In Colombia, even though geographical areas with high incidence of this disorder have been reported, the absence of a national screening program does not permit us to determine its prevalence. Objective: Establish the prevalence of hemoglobin variants in a population covered by the neonatal screening program of Clínica Colsanitas S.A., between June 2000 and December 2014, including eight capital cities in Colombia. Methods: A retrospective cross-sectional study was conducted. We collected data from reports of the neonatal hemoglobinopathy-screening program for full-term newborn babies between 5 and 15 days old. Qualitative hemoglobin analysis was performed using gel electrophoresis of blood samples taken from the babies' heels. Results: The overall prevalence of abnormal Hb was 1.3%. Within the groups of newborns affected with any hemoglobinopathy (n = 400), the most frequent abnormal structural hemoglobins found were HbS (43%), HbC (9%), fast Hb (8%). For quantitative hemoglobins, HbA2 was 3.7% and HbA kept slightly elevated in 14.7% of cases. Frequency of homozygosis for HbS was 0.01%. Barranquilla, Cartagena and Cali were the cities with the greatest frequency of hemoglobinopathies. No correlation between sex and abnormal hemoglobin was found. Discussion and conclusion: Taking in consideration data from the World Health Organization (WHO) on hemoglobinopathies, our prevalence of > 1% is considered high. Therefore, a more extended coverage and the need for a national screening program are priorities.

RESUMO Introdução: As hemoglobinopatias são doenças genéticas comuns em todo o mundo e representam um problema de saúde pública. Na Colômbia, embora existam áreas geográficas com maior risco de apresentá-las, não há programas de triagem nem estudos para estabelecer sua prevalência na população. Objetivo: Estabelecer a prevalência de variantes de hemoglobina (Hb) na população pertencente ao programa de triagem neonatal da Clínica Colsanitas S.A. entre junho de 2000 e dezembro de 2014, em oito cidades do país. Métodos: Estudo transversal retrospectivo. Os registros do programa de triagem neonatal das hemoglobinopatias foram revistos para a informação dos resultados de eletroforese de hemoglobina em pH alcalino, praticada no sangue dos recém-nascidos com idades compreendidas entre 5-15 dias. Resultados: A prevalência geral de Hb anormal foi de 1,3%. Dentro dos grupos de recém-nascidos afetados com qualquer hemoglobinopatia (n = 400), as hemoglobinas anormais estruturais mais frequentes foram hemoglobina S (HbS) (43%), hemoglobina C (HbC) (9%) e Hb rápida (8%). Para as Hb quantitativas, o aumento da hemoglobina A2 (HbA2) foi de 3,7%, e a hemoglobina A (HbA) aumentada permaneceu ligeiramente elevada em 14,7% casos. A frequência de homozigotos para HbS foi de 0,01%. Barranquilla, Cartagena e Cali foram as cidades com maior frequência de hemoglobinopatias. Não houve associação entre sexo e presença de algum tipo de Hb. Discussão e conclusão: A prevalência global de hemoglobinopatias em nosso estudo foi alta (> 1%) de acordo com os critérios da Organização Mundial de Saúde (OMS). Portanto, há a necessidade de implementação de programas de triagem neonatal com maior cobertura nacional para as hemoglobinopatias.

Autoverification of the automated blood cell counter (CBC) in a reference laboratory in Bogota, Colombia / Autoverificação do contador de células automatizado de sangue (CBC) em um laboratório de referência em Bogotá, Colômbia

ABSTRACT Introduction: The clinical laboratory is part of the group of actors in health systems that are under increasing pressure by users and administrators to increase their productivity in order to respond efficiently to the increased volume of patients, optimizing costs and professional time. This pressure forced laboratories to perform a full review of their procedures and develop technical, logistical and computational tools to enable excellent response times. Objective: This study aimed to evaluate the implementation of the automated blood cell counter autoverification process and its impact on the safety of patients. Methods: Verification rules were designed in the connectivity software, based on manual validation criteria for laboratory professionals, according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI) Guideline Auto10-A and the International Consensus Group for Hematology Review (ISLH). The autoverification percentage was established, and non-conforming product (NCP) percentages were estimated before and after the procedure. Pilot tests were also performed in different days so as to adjust the process. Results: 53.4% of automated blood cell counters autoverification were achieved, and, subsequently in the audit of 18 months, 60% was reached due to verification adjustments in the delta programmed filter. The NCPs rose from 0.065% to 0.0036% from the beginning to the end of the process. Conclusion: The autoverification process enabled to reduce the variability associated with human intervention, therefore the professional is able to focus on the pathological report analysis, reducing the risk of errors and advocating greater importance on patient safety.

RESUMO Introdução: O laboratório clínico é parte do grupo de atores nos sistemas de saúde, que são cada vez mais pressionados por usuários e administradores para aumentar sua produtividade a fim de responder de forma eficiente ao aumento do volume de pacientes, otimizando custos e tempo dos funcionários. Essa pressão forçou laboratórios para efetuar uma revisão completa de seus procedimentos, bem como desenvolver instrumentos técnicos, logísticos e computacionais para permitir excelentes tempos de resposta. Objetivo: Neste estudo, a implementação do processo automatizado de autoverificação do hemograma e seu impacto sobre a segurança do paciente são avaliados. Métodos: Regras de verificação foram construídas no software de conectividade com base em critérios de validação manual dos profissionais de laboratório, de acordo com as orientações do Clinical and Laboratory Standards Institute (CLSI) de Guideline Auto10-A e do International Consensus Group for Hematology Review (ISLH). A percentagem de autoensaio foi estabelecida e as de produtos não conformes (PNC), estimadas antes e depois do procedimento. Testes piloto foram realizados em dias diferentes para ajustar o processo. Resultados: Cinquenta e três por cento da autoverificação dos hemogramas automatizados foram alcançados e, posteriormente, na auditoria dos 18 meses, foram obtidos 60% devido a ajustes na verificação do filtro delta programado. Os PNCs aumentaram de 0,065% a 0,0036% desde o início até ao final do processo. Conclusão: O processo do autoverificação ajudou a reduzir a variabilidade associada à intervenção humana, portanto o profissional pode concentrar-se na análise de relatórios patológicos, reduzindo o risco de erros e dando maior importância para a segurança do paciente.

Exactitud del test ADN-HPV para la detección de la enfermedad cervical de alto grado (NIC 2+) en mujeres con anormalidades citológicas (ASC-US y LSIL), afiliadas a la seguridad social en Bogotá (Colombia) / Accuracy of HPV-DNA test for detecting high-grade disease (CIN 2+)in women with minor cytological abnormalities (ASC-US and LSIL)

Objetivo: evaluar la exactitud de la prueba ADNHPV en el diagnóstico de lesiones premalignas cervicales de alto grado (HSIL, por sus siglas en inglés) en mujeres con alteraciones citológicas ASC-US (células escamosas atípicas de significado indeterminado) y LSIL (lesión escamosa intraepitelial de bajo grado). Metodología: estudio de validez diagnóstica y de cohorte transversal, realizado en mujeres con diagnóstico citológico de ASC-US o LSIL entre octubre de 2006 y enero de 2008, pertenecientes al Programa de Tamizaje de Cáncer de Cérvix de una aseguradora privada en Bogotá (Colombia). Se comparó el resultado de la colposcopia y de la prueba de ADN-HPV con la patología del cérvix como patrón de oro. Resultados: de las 429 mujeres, 344 (80,2%) presentaron ASC-US y 85 (19,8%) LSIL. Las prevalencias de infección por HPV de alto riesgo fueron 52,9% y 75,7% en pacientes con reporte citológico de ASC-US y LSIL, respectivamente. A las 379 de las 425 pacientes se les practicó biopsia, 24 (6,3%) dieron positivas para HSIL. La sensibilidad de la prueba ADN-HPV para detectar lesiones de alto grado (NIC 2+) en las mujeres con reportes de citología ASC-US y LSIL fue 88% y la especificidad fue 44%. En 21 (87.5%) de los 24 casos de HSIL se detectó la presencia de HPV de alto riesgo. Conclusión: debido a que la prueba ADN-HPV tiene una sensibilidad superior a la citología cervicovaginal (CCV), ésta puede considerarse una alternativa útil para estratificar el riesgo y mejorar la aproximación diagnóstica de lesiones premalignas del cuello uterino en mujeres con reporte de ASC-US.

Objective: evaluating the accuracy of the HPV DNA test as a complementary test for diagnosing highgrade cervical disease (high-grade squamous intra epithelia lesions-HSIL) in women with minor cytological abnormalities (atypical squamous cells of undetermined significance ASC-US) and low-grade squamous intraepithelial lesions (LSIL). Methodology: a diagnostic validity study based on a cross-sectional design was applied to 429 women who had had a cytological report of ASC-US and/or LSIL who were attending a health maintenance organisation’s cervical cancer screening programme in Bogotá, Colombia between January 2006 and October 2008. Colposcopy reports and HPV-DNA testresultswerecomparedwithpathologicalreports which were considered the gold standard. Results: 344 (80.2%) of the 429 women had a cytological report of ASC-US and 85 (19.8%) of them one for LSIL. High-risk HPV infection prevalence was 52.9% and 75.7% in patients having an ASC-US and LSIL report, respectively. A biopsy specimen was obtained in 379 of the 429 participants and 24 high-grade cases (6.3%) were diagnosed. DNA-HPV test sensitivity was 88% and specificity was 44% for detecting high-grade disease (CIN 2+) in women having an ASC-US and LSIL cytology report . The presence of high-risk HPV virus was detected in 21 of the 24 HSIL cases (87.5%). Conclusion: the DNA-HPV test’s higher sensitivity compared to the PAP smear (due to high NPV) means that it could be considered a useful tool for stratifying risk and improving the diagnostic approach to premalignant lesions of the uterine cervix in patients having a cytological report of ASC-US.

[Human T-lymphotropic virus (HTLV I/II) seroprevalence amongst blood-donors in a hospital Bogotá, Colombia,between 1999 and 2004]. / Seroprevalencia de Anticuerpos para Virus Linfotrópicos Humanos (HTLV I/II) en donantes de sangre de una Clínica de Bogotá, Colombia. 1999-2004.

OBJECTIVE: This study was aimed at determining anti-human T-lymphotropic virus I/II (HTLV I/II) seroprevalence amongst blood-donors at the Clínica Reina Sofía in Bogotá, Colombia between 1999 and 2004. METHODS: All people donating blood at the Clínica Reina Sofía were selected for anti-HTLV I/II testing; a survey was carried out which focused on risk factors. All blood donations were screened by using enzyme immunolinked assay (ELISA); repeatedly reactive serum samples were confirmed as being HTLV I or HTLV II by using Western blot (WB). RESULTS: 8,913 blood donors, 5,883 (66 %) males and 3,030 (34 %) females having a mean age of 37 were included in the study; 26 (0,3 %) were repeatedly reactive in ELISA tests, 6 (0,07 %) of whom were confirmed by using Western blot (WB). Our findings revealed 0,07 % HTLV seroprevalence amongst blood-donors, in line with other European and South-American countries. CONCLUSION: Although our findings suggest low HTLV I/II seroprevalence, blood-donors should be routinely screened to minimise transmission due to occult HTLV I/II infection in Colombia.

Seroprevalencia de Anticuerpos para Virus Linfotrópicos Humanos (HTLV I/II) en donantes de sangre de una Clínica de Bogotá, Colombia. 1999-2004 / Human T-lymphotropic virus (HTLV I/II) seroprevalence amongst blood-donors in a hospital Bogotá, Colombia,between 1999 and 2004

Objetivo: Determinar la prevalencia de anticuerpos para HTLV I/II, en los donantes de sangre del Banco de Sangre de la Clínica Reina Sofía, ubicada en Bogotá, Colombia. Métodos: Fueron incluidas las muestras de todos los donantes de sangre en el período comprendido entre Abril de 1999 y Agosto de 2004. A estas muestras se les realizó un ELISA para identificación de los virus HTLV I/II; a los donantes con muestras reactivas se les tomó una nueva muestra, la cual se confirmó mediante Western blot (WB). Se analizaron las encuestas de todos los donantes con pruebas reactivas para HTLV I/II en el periodo descrito y se diligenció un formulario con las variables. Resultados: La población total de donantes de sangre estudiados en los cinco años fue de 8 913 donantes, 5 883 (66 por ciento) hombres y 3 030 (34 por ciento) mujeres, con un promedio de 37 años; de los cuales 26 (0,3 por ciento) tuvieron ELISA doblemente reactivo para HTLV I/II y, de estos, solo seis pacientes fueron confirmados mediante WB, los cuales representan una prevalencia de 0,07 por ciento Conclusión: Aunque nuestros hallazgos sugieren una baja seroprevalencia para HTLV I/II, nos permiten resaltar la importancia de implantar la prueba de detección de anticuerpos contra estos virus en todos los Bancos de Sangre del país junto con las demás pruebas que ya son indispensables según la legislación colombiana para poder suministrar sangre y hemocomponentes de calidad.

Objective: This study was aimed at determining anti-human T-lymphotropic virus I/II (HTLV I/II) seroprevalence amongst blood-donors at the Clínica Reina Sofía in Bogotá, Colombia between 1999 and 2004. Methods: All people donating blood at the Clínica Reina Sofía were selected for anti-HTLV I/II testing; a survey was carried out which focused on risk factors. All blood donations were screened by using enzyme immunolinked assay (ELISA); repeatedly reactive serum samples were confirmed as being HTLV I or HTLV II by using Western blot (WB). Results: 8 913 blood donors, 5 883 (66 percent) males and 3,030 (34 percent) females having a mean age of 37 were included in the study; 26 (0,3 percent) were repeatedly reactive in ELISA tests, 6 (0,07 percent) of whom were confirmed by using Western blot (WB). Our findings revealed 0,07 percent HTLV seroprevalence amongst blood-donors, in line with other European and South-American countries. Conclusion: Although our findings suggest low HTLV I/II seroprevalence, blood-donors should be routinely screened to minimise transmission due to occult HTLV I/II infection in Colombia.