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The widespread presence of arsenic (As) and fluoride (F-) in groundwater poses substantial risks to human health on a global scale. These elements have been identified as the most prevalent geogenic contaminants in groundwater in northern Mexico. Consequently, this study aimed to evaluate the human health and ecological risks associated with the content of As and F- in the Meoqui-Delicias aquifer, which is in one of Mexico's most emblematic irrigation districts. Concentrations of As and F- were measured in 38 groundwater samples using ICP-MS and ion chromatography, respectively. Overall, these elements showed a similar trend across the aquifer, revealing a positive correlation between them and pH. The concentration of As and F- in the groundwater ranged from 5.3 µg/L to 303 µg/L and from 0.5 mg/L to 8.8 mg/L, respectively. Additionally, the levels of As and F- surpassed the established national standards for safe drinking water in 92% and 97% of samples, respectively. Given that groundwater is used for both agricultural purposes and human activities, this study also assessed the associated human health and ecological risks posed by these elements using Monte Carlo simulation and Species Sensitivity Distribution. The findings disclosed a significant noncarcinogenic health risk associated with exposure to As and F-, as well as an unacceptable carcinogenic health risk to As through water consumption for both adults and children. Furthermore, a high ecological risk to aquatic species was identified for F- and high to medium risks for As in the sampling sites. Therefore, the findings in this study provide valuable information for Mexican authorities and international organizations (e.g., WHO) about the adverse effects that any exposure without treatment to groundwater from this region represents for human health.
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Arsénico , Monitoreo del Ambiente , Fluoruros , Agua Subterránea , Método de Montecarlo , Contaminantes Químicos del Agua , Agua Subterránea/química , Fluoruros/análisis , Contaminantes Químicos del Agua/análisis , Arsénico/análisis , México , Humanos , Medición de Riesgo , Agua Potable/químicaRESUMEN
Latin America presents a high prevalence of Helicobacter pylori(Hp) infection. Between1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decreasein this infection. Updating the frequency of Hp is crucial due to its associated health impact. OBJECTIVE: Our objective was to describe the trend in Hp infection in patients undergoingambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. MATERIALS AND METHODS: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trendswere described through time series analysis. A Poisson model was constructed to estimatethe risk of infection, adjusted for age and gender. RESULTS: 11,355 patients were included[66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequencyof Hp infection [RR 1.13; (95% CI: 1.08-1.18)].Hp frequency infection decreased significantlyfrom 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64;(95% CI: 0.55-0.74)]. A progressive decline in Hp infectiontrend was projected, reaching values close to 25% by year 2025. CONCLUSION: A significantreduction in Hpinfection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.
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Infecciones por Helicobacter , Helicobacter pylori , Humanos , Chile/epidemiología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Anciano , Prevalencia , Endoscopía del Sistema Digestivo , Adulto Joven , Endoscopía Gastrointestinal , Factores de TiempoRESUMEN
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, yet its current treatments are limited to stopping disease progression. Moreover, the effectiveness of these treatments remains uncertain due to the heterogeneity of the disease. Therefore, it is essential to identify disease subtypes at a very early stage. Current data-driven approaches can be used to classify subtypes during later stages of AD or related disorders, but making predictions in the asymptomatic or prodromal stage is challenging. Furthermore, the classifications of most existing models lack explainability, and these models rely solely on a single modality for assessment, limiting the scope of their analysis. Thus, we propose a multimodal framework that utilizes early-stage indicators, including imaging, genetics, and clinical assessments, to classify AD patients into progression-specific subtypes at an early stage. In our framework, we introduce a tri-modal co-attention mechanism (Tri-COAT) to explicitly capture cross-modal feature associations. Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (slow progressing = 177, intermediate = 302, and fast = 15) were used to train and evaluate Tri-COAT using a 10-fold stratified cross-testing approach. Our proposed model outperforms baseline models and sheds light on essential associations across multimodal features supported by known biological mechanisms. The multimodal design behind Tri-COAT allows it to achieve the highest classification area under the receiver operating characteristic curve while simultaneously providing interpretability to the model predictions through the co-attention mechanism.
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In the development of biosimilar products to Neulasta, it is essential to determine the intact molecular mass and confirm precise PEGylation sites. In this study, we applied a combination of techniques, including post-column addition of triethylamine in reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) to determine the intact molecular mass, and in-source fragmentation (ISF) and higher-energy collision dissociation-tandem mass spectrometry (HCD-MS/MS) to identify the PEGylation site. Our results show that both the pegfilgrastim biosimilar candidate and Neulasta lots are mono-PEGylated at the N-terminal end. Furthermore, we show that the combined ISF and HCD-MS/MS method can be used for identifying the PEGylation sites in the diPEGylated variant of pegfilgrastim. The diPEGylated variant has modification sites at the N-terminal end and a lysine at position 35 in the protein sequence.
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Biosimilares Farmacéuticos , Espectrometría de Masas en Tándem , Espectrometría de Masas en Tándem/métodos , Biosimilares Farmacéuticos/química , Filgrastim , Polietilenglicoles/químicaRESUMEN
RESUMEN Latinoamérica presenta una alta prevalencia de infección por Helicobacter pylori (Hp). Entre 1996-2003 la prevalencia en Santiago de Chile fue del 70%; estudios recientes presentan una disminución en esta infección. Actualizar la frecuencia de Hp es fundamental debido a su impacto en la salud asociado. Objetivo: Nuestro objetivo fue describir la tendencia de la infección por Hp en pacientes que asisten a endoscopía digestiva alta (EDA) ambulatoria en una población chilena. Materiales y métodos: Se realizó un estudio observacional retrospectivo de pacientes mayores de 18 años que asistieron a una primera EDA con test rápido de ureasa entre 2010-2020. La tendencia en el tiempo fue descrita mediante análisis de series de tiempo. Se construyó un modelo Poisson para estimar el riesgo de infección, ajustado por edad y sexo. Resultados: Se incluyeron 11 355 pacientes [66,9% mujeres; edad media 52 años; Hp 41,6%]. El sexo masculino presentó una mayor frecuencia de infección por Hp [RR 1,13; (IC95%:1,08-1,18)]. La frecuencia de Hp disminuyó significativamente desde 45,1% en 2010 hasta 29% en 2020, con 36% menor probabilidad de presentar infección por Hp en 2020 con respecto al 2010 [RR 0,64; (IC95%:0,55-0,74)]. Se proyectó un descenso progresivo en la tendencia de infección por Hp hasta valores cercanos al 25% para el año 2025. Conclusión: Se observó una reducción significativa en la infección por Hp entre los años 2010-2020. Esta disminución pudiese ser explicada mediante la incorporación de políticas públicas de salud en la última década asociadas a cambios sociosanitarios.
ABSTRACT Latin America presents a high prevalence of Helicobacter pylori (Hp) infection. Between 1996-2003, the prevalence in Santiago, Chile, was 70%; recent studies indicate a decrease in this infection. Updating the frequency of Hp is crucial due to its associated health impact. Objective: Our objective was to describe the trend in Hp infection in patients undergoing ambulatory esophagogastroduodenoscopy (EGD) in a Chilean population. Materials and methods: A retrospective observational study was conducted on patients over 18 years old who attended a first EGD with a rapid urease test between 2010-2020. Time trends were described through time series analysis. A Poisson model was constructed to estimate the risk of infection, adjusted for age and gender. Results: 11,355 patients were included [66.9% females; mean age 52 years; Hp 41.6%]. Male gender presented a higher frequency of Hp infection [RR 1.13; (95% CI: 1.08-1.18)]. Hp frequency infection decreased significantly from 45.1% in 2010 to 29% in 2020, with a 36% lower probability of Hp infection in 2020 compared to 2010 [RR 0.64; (95% CI: 0.55-0.74)]. A progressive decline in Hp infection trend was projected, reaching values close to 25% by year 2025. Conclusion: A significant reduction in Hp infection was observed between 2010-2020. This decrease could be explained by the implementation of public health policies in the last decade associated with socio-sanitary changes.
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BACKGROUND: L-asparaginase (L-ASNase) is an essential component of chemotherapy strategies due to its differential action between normal and leukemic cells. Recently, concerns about the efficiency of commercial formulations administered in developing countries have been reported, and available methods have limitations for directly determining the quality of the formulation of the medications. PROCEDURE: We developed a cell-based protocol to analyze the activity of different L-ASNase formulations used in Colombia to induce apoptosis of the NALM-6 cell line after 24, 48, and 72 hours, using flow cytometry. Then we compared results and determined the statistically significant differences. RESULTS: Three statistically different groups, ranging from full to no activity against leukemic cells, using 0.05, 0.5, and 5.0 IU/ml concentrations, were identified. Group 1 (asparaginase codified [ASA]2-4) exhibited very low to no activity against B-cell acute lymphoblastic leukemia (B-ALL) cells. Group 2 (ASA6) exhibited intermediate-level activity, and group 3 (ASA1 and ASA5) exhibited high activity. CONCLUSIONS: Differences found between the therapeutic formulations of L-ASNase distributed in Colombia raise concerns about the quality of the treatment administered to patients in low- and middle-income countries. Therefore, we recommend a preclinical evaluation of formulations of L-ASNase in order to prevent therapeutical impacts on the outcome of ALL patients.
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Antineoplásicos , Asparaginasa , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Antineoplásicos/uso terapéutico , Asparaginasa/uso terapéutico , Línea Celular , Colombia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológicoRESUMEN
Polygenic risk scores (PRS) are increasingly used to estimate the personal risk of a trait based on genetics. However, most genomic cohorts are of European populations, with a strong under-representation of non-European groups. Given that PRS poorly transport across racial groups, this has the potential to exacerbate health disparities if used in clinical care. Hence there is a need to generate PRS that perform comparably across ethnic groups. Borrowing from recent advancements in the domain adaption field of machine learning, we propose FairPRS - an Invariant Risk Minimization (IRM) approach for estimating fair PRS or debiasing a pre-computed PRS. We test our method on both a diverse set of synthetic data and real data from the UK Biobank. We show our method can create ancestry-invariant PRS distributions that are both racially unbiased and largely improve phenotype prediction. We hope that FairPRS will contribute to a fairer characterization of patients by genetics rather than by race.
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Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Biología Computacional , Factores de Riesgo , Fenotipo , Herencia MultifactorialRESUMEN
Wastewater-based epidemiology offers a time- and cost-effective way to monitor SARS-CoV-2 spread in communities and therefore represents a complement to clinical testing. WBE applicability has been demonstrated in a number of cases over short-term periods as a method for tracking the prevalence of SARS-CoV-2 and an early-warning tool for predicting outbreaks in the population. This study reports SARS-CoV-2 viral loads from wastewater treatment plants (WWTPs) and hospitals over a 6-month period (June to December 2020). Results show that the overall range of viral load in positive tested samples was between 1.2 × 103 and 3.5 × 106 gene copies/l, unveiling that secondary-treated wastewaters mirrored the viral load of influents. The interpretation suggests that the viral titers found in three out of four WWTPs were associated to clinical COVID-19 surveillance indicators preceding 2-7 days the rise of reported clinical cases. The median wastewater detection rate of SARS-CoV-2 was one out of 14,300 reported new cases. Preliminary model estimates of prevalence ranged from 0.02 to 4.6% for the studied period. This comprehensive statistical and epidemiological analysis demonstrates that the applied wastewater-based approach to COVID-19 surveillance is in general consistent and feasible, although there is room for improvements.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , COVID-19/epidemiología , Humanos , México/epidemiología , ARN Viral/genética , SARS-CoV-2/genética , Aguas ResidualesRESUMEN
OBJECTIVES: To: 1. Describe the frequency of viral RNA detection in stools in a cohort of patients infected with SARS-CoV-2, and 2. Perform a systematic review to assess the clearance time in stools of SARS-CoV-2. METHODS: We conducted a prospective cohort study in two centers between March and May 2020. We included SARS-CoV-2 infected patients of any age and severity. We collected seriated nasopharyngeal swabs and stool samples to detect SARS-CoV-2. After, we performed a systematic review of the prevalence and clearance of SARS-CoV-2 in stools (PROSPERO-ID: CRD42020192490). We estimated prevalence using a random-effects model. We assessed clearance time by using Kaplan-Meier curves. RESULTS: We included 32 patients; mean age was 43.7±17.7 years, 43.8% were female, and 40.6% reported gastrointestinal symptoms. Twenty-five percent (8/32) of patients had detectable viral RNA in stools. The median clearance time in stools of the cohort was 11[10-15] days. Systematic review included 30 studies (1392 patients) with stool samples. Six studies were performed in children and 55% were male. The pooled prevalence of viral detection in stools was 34.6% (twenty-four studies, 1393 patients; 95%CI:25.4-45.1); heterogeneity was high (I2:91.2%, Q:208.6; p≤0.001). A meta-regression demonstrates an association between female-gender and lower presence in stools (p=0.004). The median clearance time in stools was 22 days (nineteen studies, 140 patients; 95%CI:19-25). After 34 days, 19.9% (95%CI:11.3-29.7) of patients have a persistent detection in stools. CONCLUSIONS: Detection of SARS-CoV-2 in stools is a frequent finding. The clearance of SARS-CoV-2 in stools is prolonged and it takes longer than nasopharyngeal secretions.
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COVID-19 , SARS-CoV-2 , Adulto , COVID-19/diagnóstico , COVID-19/epidemiología , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , ARN Viral , Esparcimiento de VirusRESUMEN
Parkinson's disease (PD) is the second most common neurodegenerative disease and presents a complex etiology with genomic and environmental factors and no recognized cures. Genotype data, such as single nucleotide polymorphisms (SNPs), could be used as a prodromal factor for early detection of PD. However, the polygenic nature of PD presents a challenge as the complex relationships between SNPs towards disease development are difficult to model. Traditional assessment methods such as polygenic risk scores and machine learning approaches struggle to capture the complex interactions present in the genotype data, thus limiting their discriminative capabilities in diagnosis. On the other hand, deep learning models are better suited for this task. Nevertheless, they encounter difficulties of their own such as a lack of interpretability. To overcome these limitations, in this work, a novel transformer encoder-based model is introduced to classify PD patients from healthy controls based on their genotype. This method is designed to effectively model complex global feature interactions and enable increased interpretability through the learned attention scores. The proposed framework outperformed traditional machine learning models and multilayer perceptron (MLP) baseline models. Moreover, visualization of the learned SNP-SNP associations provides not only interpretability to the model but also valuable insights into the biochemical pathways underlying PD development, which are corroborated by pathway enrichment analysis. Our results suggest novel SNP interactions to be further studied in wet lab and clinical settings.
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INTRODUCTION: Helicobacter pylori infection affects approximately 70% of the Chilean population. It is a public health problem whose eradication treatment is part of the explicit health guarantees in Chile. OBJECTIVES: Characterize the most widely used H. pylori first-line eradication therapies in our environment and evaluate their efficacy. METHODS: A retrospective observational study was carried out where, in patients with certified H. pylori infection, the eradication therapy indicated by the treating physician, its efficacy, adherence and adverse effects, in addition to the eradication certification method used, were evaluated. RESULTS: 242 patients and 4 main therapies were analyzed: standard triple therapy, dual therapy, concomitant therapy, and bismuth quadruple therapy. Eradication rates of 81.9% (95% CI 74.44-87.63), 88.5% (95% CI 73.13-95.67), 93.7% (95% CI 78.07-98.44) and 97.6% (95% CI 84.81-99.67) were observed respectively, with concomitant therapy (RR: 1.14; 95% CI 1.01-1.29; p=.028) and quadruple therapy with bismuth (RR: 1.19; 95% CI 1.09-1.31; p<.001) being significantly more effective than standard triple therapy. Regarding the rate of reported adverse effects, it was 58.5% (95% CI 50.66-65.92), 35.4% (95% CI 24.6-48.11), 22.9% (95% CI 81-37.14) and 63.4% (95% CI 47.8-76.64), having the dual and concomitant therapy significantly fewer adverse effects compared with standard therapy. CONCLUSIONS: Quadruple therapies are superior to standard triple therapy and should be considered as first-line treatment in Chile. Dual therapy is promising. More studies will be required to determine which therapies are most cost-effective.
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Infecciones por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapéutico , Antibacterianos/efectos adversos , Bismuto/uso terapéutico , Chile , Quimioterapia Combinada , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Inhibidores de la Bomba de Protones/uso terapéuticoAsunto(s)
Humanos , Recién Nacido , Lactante , Preescolar , Niño , Cuidados Críticos , Tratamiento de Urgencia , Medicina de Urgencia Pediátrica , Terapia por Inhalación de Oxígeno/instrumentación , Arritmias Cardíacas/terapia , Insuficiencia Respiratoria/terapia , Choque/terapia , Cardiotónicos , Reanimación Cardiopulmonar , Paro Cardíaco/diagnóstico , Paro Cardíaco/terapia , Intubación Intratraqueal/métodosRESUMEN
The Shiga toxin associated (Stx) hemolytic uremic syndrome (HUS) is an important cause of acute renal failure (ARF) and the most common cause of thrombotic microangiopathy (TMA) in pediatrics. Primary atypical HUS (aHUS) is a rare disease due to a genetic defect in the alternative complement pathway. Both diseases may share clinical and laboratory elements, making differential diagnosis difficult, such as the presence of diarrhea in aHUS or complement alterations in HUS-Stx. The treatment and prognosis of both diseases is completely different. We report a 15-year-old male with severe HUS. After a self-limited diarrheal syndrome, he had a severe TMA and ARF, requiring renal replacement therapy. An extensive etiological study was carried out, ruling out the main causes of TMA. Alterations in complement factors were observed. Finally, the diagnosis of HUS-Stx was established. The patient evolved favorably with recovery of renal function.
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Humanos , Masculino , Niño , Adolescente , Lesión Renal Aguda/etiología , Síndrome Hemolítico Urémico Atípico/complicaciones , Síndrome Hemolítico Urémico Atípico/diagnóstico , Enfermedades del Sistema Inmune , Pronóstico , Toxina Shiga , Diarrea/complicacionesRESUMEN
ABSTRACT Background: Antimicrobial compounds are associated with a wide range of adverse events (AE) and some of them can be potentially preventable. Aim: To characterize AE associated with antimicrobial compounds. Patients and Methods: Retrospective analysis of AEs reported to the National Pharmacological Surveillance System from 2014 to 2017 in a regional hospital. Severity, causality and preventability were analyzed. Results: Sixty events were observed in 56 patients aged 2 months to 96 years. Cases were registered mostly in hospitalized patients. The most frequent AEs were skin disorders (56.7%), followed by hepatobiliary (13.3%), and CNS events (10%). Blood, kidney, respiratory gastrointestinal and immunological disorders were less frequently registered, including cases with anaphylactic shock and Stevens-Johnson syndrome (SJS). Causal analysis indicated a definitive association in 8.3%, probable in 70% and possible in 22%. Skin lesions were mostly associated with beta-lactams, hepatobiliary disorders with antituberculosis drugs and CNS manifestations with carbapenems. Cutaneous, neurological, and hepatobiliary events appeared at a median of 4, 2.5 and 10.5 days after starting the medication, respectively. AEs were managed with withdrawal of the suspected drug (83.3%) and other auxiliary therapies. AEs were categorized as severe in 22% and one case with SJS had a fatal outcome (1.7%). Preventability analysis revealed 25% of potentially avoidable events. Conclusions: Antimicrobial AE involved a wide diversity of compounds, occurred in different hospitalization units, affected patients of a wide age range and attacked different systems or organs. An important fraction was potentially avoidable.
Antecedentes: Los compuestos antimicrobianos están asociados a una amplia gama de eventos adversos (EA) y algunos de ellos pueden ser potencialmente prevenibles. Objetivos: Caracterizar los EA asociados a compuestos antimicrobianos. Pacientes y Métodos: Análisis retrospectivo de EA reportados al Sistema Nacional de Farmacovigilancia desde 2014 la 2017 en un hospital regional. Se incluyó un análisis de gravedad, causalidad y de posible prevención. Resultados: Se observaron 60 eventos en 56 pacientes de 2 meses a 96 años. Los casos se registraron principalmente en pacientes hospitalizados. Los EA más frecuentes fueron los trastornos de la piel (56,7%), seguidos de los hepatobiliares (13,3%) y del sistema nervioso central (10%). Los hematológicos, renales, respiratorios, gastrointestinales e inmunológicos se registraron con menos frecuencia, incluidos casos con shock anafiláctico y síndrome de Stevens-Johnson (SSJ). El análisis de causalidad indicó una asociación definitiva en 8.3%, probable en 70% y posible en 21.7%. Las lesiones cutáneas se asociaron principalmente a betalactámicos, los trastornos hepatobiliares a fármacos antituberculosos y las manifestaciones del SNC a carbapenémicos. Los eventos cutáneos, neurológicos y hepatobiliares se presentaron en una mediana de 4, 2,5 y 10,5 días después de iniciar el medicamento, respectivamente. Los EA se manejaron con el retiro del fármaco sospechoso (83,3%) y otras terapias auxiliares. Los EA se clasificaron como graves (21,7%) y un caso con SSJ tuvo un desenlace fatal (1,7%). Un 25% de los eventos fue potencialmente evitable. Conclusiones: Los resultados de este trabajo revelan que los AE por antimicrobianos involucran una amplia diversidad de compuestos, ocurren en diferentes unidades de hospitalización, afectan a pacientes de un amplio rango de edad y atacan diferentes sistemas u órganos.
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Humanos , Hospitales Generales , Antiinfecciosos , Chile/epidemiología , Estudios Retrospectivos , HospitalizaciónRESUMEN
This study is the first focused on the presence of SARS-CoV-2 in different freshwater environments in an urban setting. Groundwater and surface water reservoirs for drinking water as well as water from receiving rivers of the Monterrey Metropolitan Area were sampled repeatedly during a SARS-CoV-2 peak phase between October 2020 and January 2021, and viral RNA was measured by quantitative reverse transcription polymerase chain reaction. Forty-four percent of the groundwater samples had detectable viral loads between 2.6 and 38.3 copies/ml. A significant correlation between viral load and sucralose concentration in groundwater reaffirmed the hypothesis of leaching and infiltrating effluent from surface and/or failing sewage pipes and emphasized the importance of water disinfection. Twelve percent of the surface water dam samples tested positive for viral RNA, with values varying between 3.3 and 3.8 copies/ml. Finally, 13% of the river samples were positive for viral RNA, with concentrations ranging from 2.5 to 7.0 copies/ml. Untreated wastewater samples taken in the same period showed viral loads of up to 3535 copies/ml, demonstrating a dilution effect and/or wastewater facilities efficiency of three orders of magnitude. Variations in the viral loads in the groundwater and surface water over time and at the submetropolitan level generally reflected the reported trends in infection cases for Monterrey. The viral loads in the freshwater environments of Monterrey represent a low risk for recreational activities according to a preliminary risk assessment model. However, this result should not be taken lightly due to uncertainty regarding data and model constraints and the possibility of situations where the infection risk may increase considerably.
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COVID-19 , SARS-CoV-2 , Humanos , ARN Viral , Reacción en Cadena en Tiempo Real de la Polimerasa , Aguas Residuales , AguaRESUMEN
BACKGROUND: Antimicrobial compounds are associated with a wide range of adverse events (AE) and some of them can be potentially preventable. AIM: To characterize AE associated with antimicrobial compounds. PATIENTS AND METHODS: Retrospective analysis of AEs reported to the National Pharmacological Surveillance System from 2014 to 2017 in a regional hospital. Severity, causality and preventability were analyzed. RESULTS: Sixty events were observed in 56 patients aged 2 months to 96 years. Cases were registered mostly in hospitalized patients. The most frequent AEs were skin disorders (56.7%), followed by hepatobiliary (13.3%), and CNS events (10%). Blood, kidney, respiratory gastrointestinal and immunological disorders were less frequently registered, including cases with anaphylactic shock and Stevens-Johnson syndrome (SJS). Causal analysis indicated a definitive association in 8.3%, probable in 70% and possible in 22%. Skin lesions were mostly associated with beta-lactams, hepatobiliary disorders with antituberculosis drugs and CNS manifestations with carbapenems. Cutaneous, neurological, and hepatobiliary events appeared at a median of 4, 2.5 and 10.5 days after starting the medication, respectively. AEs were managed with withdrawal of the suspected drug (83.3%) and other auxiliary therapies. AEs were categorized as severe in 22% and one case with SJS had a fatal outcome (1.7%). Preventability analysis revealed 25% of potentially avoidable events. CONCLUSIONS: Antimicrobial AE involved a wide diversity of compounds, occurred in different hospitalization units, affected patients of a wide age range and attacked different systems or organs. An important fraction was potentially avoidable.
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Antiinfecciosos , Hospitales Generales , Chile/epidemiología , Hospitalización , Humanos , Estudios RetrospectivosRESUMEN
The Shiga toxin associated (Stx) hemolytic uremic syndrome (HUS) is an important cause of acute renal failure (ARF) and the most common cause of thrombotic microangiopathy (TMA) in pediatrics. Primary atypical HUS (aHUS) is a rare disease due to a genetic defect in the alternative complement pathway. Both diseases may share clinical and laboratory elements, making differential diagnosis difficult, such as the presence of diarrhea in aHUS or complement alterations in HUS-Stx. The treatment and prognosis of both diseases is completely different. We report a 15-year-old male with severe HUS. After a self-limited diarrheal syndrome, he had a severe TMA and ARF, requiring renal replacement therapy. An extensive etiological study was carried out, ruling out the main causes of TMA. Alterations in complement factors were observed. Finally, the diagnosis of HUS-Stx was established. The patient evolved favorably with recovery of renal function.
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Lesión Renal Aguda , Síndrome Hemolítico Urémico Atípico , Enfermedades del Sistema Inmune , Lesión Renal Aguda/etiología , Adolescente , Síndrome Hemolítico Urémico Atípico/complicaciones , Síndrome Hemolítico Urémico Atípico/diagnóstico , Niño , Diarrea/complicaciones , Humanos , Masculino , Pronóstico , Toxina ShigaRESUMEN
BACKGROUND: Comorbidities are prevalent among Multiple Sclerosis (MS) patients. Few studies have characterized their prevalence and impact in Latin American populations. OBJECTIVE: We aim to assess the prevalence of comorbidities and their impact on the risk of physical disability across different MS phenotypes. METHODS: Cross-sectional multicenter study of patients under regular clinical care at the Programa de Esclerosis Múltiple UC and Hospital Dr. Sótero del Río in Chile. Prevalence of comorbidities was estimated from the retrospective assessment of electronic medical charts. Disease phenotypes were categorized into two groups: clinically isolated syndrome/relapsing-remitting (inflammatory group) and primary/secondary progressive MS patients (progressive group). A multivariable analysis using binary logistic regression for assessing the risk of EDSS ≥ 6.0 in each group was performed. RESULTS: A total of 453 patients was included, 71% female, mean age at onset 31 years, mean disease duration 10 years, and median EDSS 2.0 (range 0-10). In the whole sample, most prevalent comorbidities were ever-smoking (42.2%), depression/anxiety (34.9%), thyroid disease (15.7%), hypertension (11.3%) and insulin resistance/type 2 diabetes mellitus (11.0%). When assessing the risk of EDSS ≥ 6, in the inflammatory group (N = 366), age at onset (OR 1.06, 95%CI(1.02-1.11), p = 0.008), disease duration (OR 1.06, 95%CI(1.00-1.12), p = 0.039) and epilepsy comorbidity (OR 5.36, 95%CI(1.33-21.5), p = 0.018) were associated with a higher risk of disability. In the progressive group (N = 87), disease duration was a risk factor (OR 1.08 95%CI(1.02-1.16), p = 0.014), while shorter diagnostic delay (OR 0.91 95%CI(0.85-0.99), p = 0.025) and insulin resistance/type 2 diabetes mellitus comorbidity were protective factors (OR 0.18 95%CI(0.04-0.83), p = 0.028), 72% of these patients were receiving metformin. CONCLUSIONS: Comorbidities are common across different MS disease phenotypes. Epilepsy seems particularly related with a higher risk of physical disability in relapsing-remitting patients, while the role of insulin resistance/type 2 diabetes mellitus or the impact of metformin use as a protective factor should be further studied. Prospective and larger studies are still needed in order to assess the real impact of comorbidities and their management in MS outcomes.
Asunto(s)
Diabetes Mellitus Tipo 2 , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Adulto , Chile , Comorbilidad , Estudios Transversales , Diagnóstico Tardío , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple Recurrente-Remitente/epidemiología , Fenotipo , Prevalencia , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a chronic immune mediated disease and the progressive phase appears to have significant neurodegenerative mechanisms. The classification of the course of progressive MS (PMS) has been re-organized into categories of active vs. not active inflammatory disease and the presence vs. absence of gradual disease progression. Clinical trial experience to date in PMS with anti-inflammatory medications has shown limited effect. Andrographolide is a new class of anti-inflammatory agent, that has been proposed as a potential drug for autoimmune disorders, including MS. In the present trial, we perform an exploratory pilot study on the efficacy and safety of andrographolide (AP) compared to placebo in not active PMS. METHODS: A pilot clinical trial using 140 mg oral AP or placebo twice daily for 24 months in patients with not active primary or secondary progressive MS was conducted. The primary efficacy endpoint was the mean percentage brain volume change (mPBVC). Secondary efficacy endpoints included 3-month confirmed disability progression (3-CDP) and mean EDSS change. RESULTS: Forty-four patients were randomized: 23 were assigned to the AP group, and 21 were assigned to the placebo group. The median baseline EDSS of both groups was 6.0. Annualized mPBVC was - 0.679% for the AP group and - 1.069% for the placebo group (mean difference: -0.39; 95% CI [- 0.836-0.055], p = 0.08, relative reduction: 36.5%). In the AP group, 30% had 3-CDP compared to 41% in the placebo group (HR: 0.596; 95% CI [0.200-1.777], p = 0.06). The mean EDSS change was - 0.025 in the AP group and + 0.352 in the placebo group (mean difference: 0.63, p = 0.042). Adverse events related to AP were mild rash and dysgeusia. CONCLUSIONS: AP was well tolerated and showed a potential effect in reducing brain atrophy and disability progression, that need to be further evaluated in a larger clinical trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT02273635 retrospectively registered on October 24th, 2014.