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Epilepsy’s overall prevalence in Colombia is 1.13%. Its prevalence in patients aged over 65 could be around 1.5%. Objective: describe demographic and clinical characteristics of patients older than 65 years of age with epilepsy. Materials and methods: A cross-sectional descriptive study was carried out in two high complexity hospitals in Bogotá, Colombia during 2005-2008. Demographic data were compiled and patients characterized regarding the type, frequency and diagnosis of seizures (based on ILAE classification), probable etiology, having a family background of epilepsy, and current pharmacological management. Results: 211 clinical histories were reviewed and 179 of them selected. Mean patient age was 75 (65-98) and average age at onset of epilepsy was 67.5 (7-93). 84% of the seizures were classified as being focal. The most frequently occurring diagnosis was symptomatic focal epilepsy (94.4%). 74 cases (41.3%) had an etiological diagnosis. The most important cause was cerebrovascular disease (61 patients). First generation anti-epileptic drugs were the most used ones (99%). 81/104 patients were found not to be free from epileptic episodes. Conclusions: Most seizures have a partial beginning, resulting from symptomatic partial epilepsy as a consequence of a vascular lesion. Pharmacological treatment must be considered following the first seizure. Treatment with second generation anti-epileptic drugs such as Lamotrigine, Gabapentin, Levetiracetam and Topiramate must be begun for minimizing secondary effects and low doses must be maintained from the start of treatment. Costs may limit the use of the above antiepileptic drugs, in such cases Phenytoin and Carbamazepine may be used with extreme caution.

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Introducción: La evolución de la atención farmacéutica en España, el desarrollo de las tecnologías de la información y la comunicación, los proyectos de receta electrónica, la aparición de publicaciones como el Foro de Atención Farmacéutica, el desarrollo del Bot Plus y su integración con los programas de gestión de las farmacias comunitarias nos han permitido definir una metodología de trabajo en atención farmacéutica (AF), estratificada y selectiva. Metodología: 1. Identificar el paciente destinatario del tratamiento. 2. Dispensación propiamente dicha. 3. Definición del perfil farmacoterapéutico de la farmacia. 3.1. Grupos terapéuticos. 3.2. Indicaciones terapéuticas. 4. Definición de patologías diana. 4.1. Relevancia numérica. 4.2. Relevancia terapéutica. 5. Definición del potencial de seguimiento farmacoterapéutico (SFT) de la farmacia comunitaria. 6. Elección de pacientes diana. 7. Ofrecimiento del servicio de SFT. Resultados: En las cuatro farmacias comunitarias (FC) participantes se definió el perfil farmacoterapéutico a partir de los grupos terapéuticos a nivel 1. A partir de aquí dichas farmacias definieron sus respectivas patologías diana y los posibles pacientes a los que ofrecer el servicio. Se basan en dichos resultados para establecer la formación de sus profesionales. Conclusiones: La metodología Avenzoar parte del conocimiento del paciente mediante el registro sistemático de las dispensaciones realizadas. Permite definir el perfil farmacoterapéutico de los pacientes. Permite decidir el nivel de implicación con el seguimiento de cada paciente según criterios previamente definidos. La metodología Avenzoar es compatible y complementaria con cualquier metodología de seguimiento farmacoterapéutico.

Background: Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high-risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016-2020 compared to 2004-2006 in six hospitals in Chile., Methods: Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004-2006. The incidence rate was estimated., Results: A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent-HRFN occurring in 174 patients. The median age was 7 years (IQR: 3-12 years) and 52.3% (N = 91) were male. Fifty-three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent-HRFN with an IFD incidence of 14.6% (95% CI 10.5-19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5-20.0). Compared to 2004-2006 cohort (incidence: 8.5% (95% CI 5.2-13.5)), a significant increase in incidence of 6.1% (95% CI 0.2-12.1, p = .047) was detected in cohorts between 2016 and 2020., Conclusion: We observed a significant increase in IFD in 2016-2020, compared to 2004-2006 period., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Objectives: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection., Methods: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death., Results: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported., Discussion: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Diffusion cells play a crucial role in the pharmaceutical and cosmetic fields by assessing the release and permeation of active pharmaceutical ingredients across membranes. However, commercially available glass-based devices, such as Franz diffusion cells, are expensive and fragile. The emergence of three-dimensional (3D) printing technology enables the creation of diffusion cells with cost-effective polymeric materials and resins, offering exceptional precision and custom geometries. Nonetheless, there are challenges associated with interactions between 3D printing materials and drug molecules. This work aimed to develop inert coatings for 3D-printed diffusion models. Diffusion devices were designed and 3D-printed with a stereolithography (SLA) 3D printer, and different coatings were applied. Then, two model drugs were used to evaluate drug retention by coated devices. Among the tested coatings, one of them showed great potential in preventing drug retention and was selected for subsequent experiments with different drugs and conditions. Finally, voriconazole eyedrops were used to confirm the viability of 3D-printed Franz diffusion cells as a drug release diffusion model. The favourable results obtained with the coating promote the use of 3D printing as a cost-effective manufacturing technology, capable of producing diffusion cells tailored to specific study requirements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Contact dermatitis (CD) is one of the most prevalent skin diseases. It is commonly divided into irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). Patch testing is a procedure used to support the diagnosis of ACD. This test should be interpreted along with the clinical history and morphology of the skin lesions to determine clinical relevance. Objective: To describe the sensitization patterns of patients undergoing patch testing with the Latin American baseline series. Methods: A single-center retrospective study was performed. For the study, patients older than 18 years with a clinical diagnosis of contact dermatitis, who underwent patch testing using the Latin American baseline series were considered. These tests took place at the Alma Mater Hospital of Antioquia between January 1, 2016, and December 31, 2021. Results: A total of 648 patients were included. Patch tests were positive in 63% of cases, with a mean age of 51.5 years. Around 36.6% had atopy-related diseases. The main occupation was housework (30.7%). The hands were the most affected area in the body (31%). The main allergens were nickel sulfate (34%), sodium tetrachloropalladate (24.2%), and thimerosal (8.0%). Fifteen allergens had a percentage below 1%. Hydrocortisone and budesonide did not yield positive results. Conclusion: Nickel sulfate was the most frequent allergen, and women were the most affected. The information gathered could be useful for adjusting the allergens that should be included in the regional baseline series, taking into account the frequency found.

Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN)., Objective: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group., Method: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021., Results: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04)., Conclusion: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

Introduction: Safety Rounds (SR) are an operational tool that allow knowing adherence to good practices, help identify risks and incidents in patient safety (PS), allowing improvement actions to be implemented. The objective of this work was the design of a procedure to perform SR in an Intensive Care Unit (ICU)., Methods: Preparation of a checklist for the development of SR in the ICU through the nominal group technique, with the participation of managers, middle managers and professionals from different disciplines and categories. In the first place, a group of experts agreed, based on the recommendations on good practices in PS, the definition of items, their coding, the criteria for compliance and the impact of non-compliance. Subsequently, its viability was determined through a cross-sectional study through the piloting of two SRs to adjust the items in real clinical practice conditions., Results: A specific SR model for ICUs has been obtained through a checklist. The group of experts prepared a first list made up of 39 items of 6 essential dimensions and defined the method of implementation. Mean time to complete the two SRs was 85 min, including the briefing and subsequent debriefing. After the validation pilot, the dimensions were reduced to 5, 3 items were deleted, 2 items were transferred to another dimension and 3 items related to nosocomial infections and informed consent were modified. In addition, the data sources, the compliance criteria and their relative weight were redefined. The final list was considered useful and relevant to improve practice., Conclusions: Through a consensus methodology, a checklist has been built to be used in the RS of an ICU. This model can serve as a basis for its use in healthcare services with similar characteristics., (Copyright © 2023 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Published by Elsevier España, S.L.U. All rights reserved.)

Chronic retinal diseases, such as age-related macular degeneration (AMD), are a major cause of global visual impairment. However, current treatment methods involving repetitive intravitreal injections pose financial and health burdens for patients. The development of controlled drug release systems, particularly for biological drugs, is still an unmet need in prolonging drug release within the vitreous chamber. To address this, green supercritical carbon dioxide (scCO 2 ) foaming technology was employed to manufacture porous poly(lactic-co-glycolic acid) (PLGA)-based intravitreal implants loaded with dexamethasone. The desired implant dimensions were achieved through 3D printing of customised moulds. By varying the depressurisation rates during the foaming process, implants with different porosities and dexamethasone release rates were successfully obtained. These implants demonstrated controlled drug release for up to four months, surpassing the performance of previously developed implants. In view of the positive results obtained, a pilot study was conducted using the monoclonal antibody bevacizumab to explore the feasibility of this technology for preparing intraocular implants loaded with biologic drug molecules. Overall, this study presents a greener and more sustainable alternative to conventional implant manufacturing techniques, particularly suited for drugs that are susceptible to degradation under harsh conditions., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aims to evaluate the prevalence of anemia and iron deficiency in women of reproductive age and the association with inflammation, global overweight, adiposity, and menorrhagia. A sample design of women of reproductive age from the Eastern, Central, and Havana Regions was carried out. Biochemical determinations of hemoglobin, serum ferritin, soluble transferrin receptors, leukocytes, C-reactive protein, alpha-1 acid glycoprotein, and homocysteine were performed. Serum ferritin was also adjusted by inflammation. Nutritional status was assessed, and menstrual characteristics were collected by survey. A total of 742 women were studied. The prevalence of anemia was 21.4%, iron storage deficiency at 16.0%, and erythropoietic dysfunction at 5.4%, with inflammation at 47.0% and elevated homocysteine at 18.6%. Global overweight was 46.2% and increased adiposity at 58.4%. Anemia is associated with iron deposition deficiency (OR = 3.023 (1.816-5.033)) and with erythropoietic deficiency (OR = 5.62 (3.03-10.39)), but not with inflammation, global overweight, and adiposity. Global overweight was found to be associated with inflammation (OR = 2.23 (1.41-3.53)). Anemia was associated with heavy menstrual bleeding (OR = 1.92 (1.34-2.76)). Homocysteine was associated with inflammation (OR = 2.05 (1.08-3.90)), but not with anemia. In conclusion, anemia in Cuba is classified as a moderate public health problem, but not iron deficiency. A high prevalence of overweight and obesity was found, associated with inflammation, but not with anemia or iron deficiency. Heavy menstrual bleeding is a factor associated with anemia.

Background: Bacterial bloodstream infections are a major cause of morbidity and mortality in children with cancer and episodes of fever and neutropenia (FN). The aim of this study was to evaluate the clinical outcome in children with cancer with 2 or more microorganisms isolated from blood cultures during their episodes of FN., Methods: Between 2016 and 2021, children presenting with high-risk FN, admitted to any of the 6 participating hospitals in Santiago, Chile, were included in this study if they have positive blood cultures. We compared the clinical outcome of children with 2 or more microorganisms versus those with single agent isolation., Results: A total of 1074 episodes of high-risk FN were enrolled in the study period, of which 27% (298) had positive blood cultures and 3% (32) had 2 or more microorganisms isolated from blood cultures. The most frequent identified agents were Viridans group streptococci and Escherichia coli in 20%, followed by Coagulase negative staphylococci in 14%. Children with 2 or more microorganisms presented more days of fever (7 vs. 4 days, P = 0.02), needed longer courses of antimicrobial therapy (16 vs. 14 days, P = 0.04) and had higher mortality at day 30 (13% vs. 1%, P = 0.003)., Conclusions: Children with cancer and FN with 2 or more microorganisms isolated from blood cultures had a worse clinical outcome than children with single agent isolation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Tumor-necrosis-factor-α inhibitors (anti-TNF-α) are associated with an increased risk of tuberculosis (TB) disease, primarily due to reactivation of latent TB infection (LTBI). We assessed the performance of parallel LTBI screening with tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube assays (QFT-GIT) before anti-TNF-α treatment in children with immune-mediated inflammatory disorders in a low TB-burden setting. We conducted a multicenter cohort study involving 17 pediatric tertiary centers in Spain. LTBI was defined as the presence of a positive TST and/or QFT-GIT result without clinical or radiological signs of TB disease. A total of 270 patients (median age:11.0 years) were included, mainly with rheumatological (55.9%) or inflammatory bowel disease (34.8%). Twelve patients (4.4%) were diagnosed with TB infection at screening (LTBI, n = 11; TB disease, n = 1). Concordance between TST and QFT-GIT results was moderate (TST+/QFT-GIT+, n = 4; TST-/QFT-GIT+, n = 3; TST+/QFT-GIT-, n = 5; kappa coefficient: 0.48, 95% CI: 0.36-0.60). Indeterminate QFT-GIT results occurred in 10 patients (3.7%) and were associated with young age and elevated C-reactive protein concentrations. Eleven of 12 patients with TB infection uneventfully completed standard LTBI or TB treatment. During a median follow-up period of 6.4 years, only 2 patients developed TB disease (incidence density: 130 (95% CI: 20-440) per 100,000 person-years), both probable de novo infections., Conclusion: A substantial number of patients were diagnosed with LTBI during screening. The dual strategy identified more cases than either of the tests alone, and test agreement was only moderate. Our data show that in children in a low TB prevalence setting, a dual screening strategy with TST and IGRA before anti-TNF-α treatment is effective., What Is Known: • The optimal screening strategy for latent tuberculosis in children with immune-mediated inflammatory disorders remains uncertain. • Children receiving anti-TNF-α drugs are at increased risk of developing severe tuberculosis disease., What Is New: • A dual screening strategy, using TST and an IGRA assay, identified more children with latent tuberculosis than either of the tests alone. • Identification and treatment of latent tuberculosis before initiation of anti-TNF-α therapy averted incident tuberculosis cases., (© 2022. The Author(s).)

Hypertransaminasemia is a frequent finding in pediatrics, which could reflect potentially treatable serious disease. The aim of this document is to establish, by reviewing the available evidence, a consensus for an adequate management of hypertransaminasemia, from its detection until the study is complete. To this end, a working group was formed with the participation of members of the Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP), the Spanish Association of Primary Care Pediatrics (AEPap) and the Spanish Society of Primary Care Pediatrics (SEPEAP). Twenty-one recommendations are established with a marked practical component that will be useful in hospital clinical practice and primary care., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.

Background: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO)., Methods: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes., Results: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity., Conclusion: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin., (Copyright © 2021. Published by Elsevier Ltd.)

The management of Helicobacter pylori infection in children is a consistent problem in clinical practice. Over the years, many questions have been raised regarding symptoms associated with the infection, the diagnostic methods and type of treatment. What is most controversial is determining the criteria that enable us to initiate and carry out the study in children. In the last 10 years, pediatricians have followed the joint ESPGHAN/NASPGHAN guidelines published in 2011 and updated in 2017 in the management of H. pylori in children. This document aims to unify the study indication criteria as well as the diagnosis and treatment recommendations for H. pylori infection in children and adolescents, so they can be used in both Primary and Hospital care., (Copyright © 2021 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

This study concerns Cr(VI) removal using zeolites in a batch system for tannery effluent. In the initial stage, natural zeolite (ZN) and synthetic zeolite (ZS) were characterized, obtaining a Si/Al ratio of 4.64 and 1.60, and with predominant clinoptilolite and faujasite phases, the surface area of 9.34 and 25.82 m 2 /g and cation exchange capacity of 84.05 and 188.72 meq/100 g, respectively. Subsequently, ZN and ZS were activated with HCl and NaOH. Through preliminary tests, with a solution of K 2 Cr 2 O 7 , it was determined that the highest Cr(VI) removal for both, ZN and ZS, was with NaOH activation, obtaining 82 and 56% removal, respectively. According to Ecuadorian regulations, the Cr(VI) concentration exceeds the maximum permissible limits on the tannery effluent. For this effluent, it was determined that the highest Cr(VI) removal, 45%, is obtained with 1 g of ZN activated with NaOH and 100 mL of effluent. With ZN-NaOH, removal tests were carried out in a fixed bed with 5, 10, and 20 g of natural zeolite. The natural zeolite also has chromium removal capacity in the bed system, achieving similar removals to those obtained in the batch experiments, but decreasing the treatment time. Thus, both natural and synthetic zeolites can remove Cr(VI) in tannery effluents, achieving this effluent with permissible limits., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Introduction: Maternal immunization is aimed at reducing morbidity and mortality in pregnant women and their newborns. Updated evidence synthesis of maternal-fetal outcomes is constantly needed to ensure that the risk-benefit of vaccination during pregnancy remains positive., Methods: An overview of systematic reviews (OoSRs) was performed. We searched The Cochrane Library, MEDLINE and EMBASE for SRs including recommended vaccines for maternal immunization reporting the following: abortion, stillbirth, chorioamnionitis, congenital anomalies, microcephaly, neonatal death, neonatal infection, preterm birth (PTB), low birth weight (LBW), maternal death and small for gestational age (SGA) from 2010 to April 2019. Quality and overlap of SRs was assessed., Results: Seventeen SRs were identified, eight of them included meta-analysis; quality was high in three SRs, moderate in six SRs, low in two SRs, and critically low in six SRs. Stillbirth and PTB were the most frequently reported outcomes by 15 and 13 SRs, respectively, followed by abortion (9 SRs), congenital anomalies (9 SRs), SGA (8 SRs), neonatal death (8 SRs), LBW (4 SRs), chorioamnionitis (3 SRs), maternal death (1 SR). SRs included mainly observational evidence for influenza and Tdap vaccines (11 SRs and 4 SRs, respectively); limited evidence was found for hepatitis (1 SR), yellow fever (1 SR), and meningococcal (1 SR) vaccines. Most of the SRs found no effect. Eight SRs found benefit/protection of influenza vaccine (for stillbirth, neonatal death, preterm birth, LBW), or Tdap vaccine (for preterm birth and SGA); one found a probable risk (chorioamnionitis/Tdap). The SRs for Hepatitis B, meningococcal and yellow fever vaccines were inconclusive., Conclusions: Definite risks were not identified for any vaccine and outcome; however better evidence is needed for all outcomes and vaccines. The available evidence in the SRs to support vaccine safety was based mainly on observational data. More RCTs with adequate reporting of maternal-fetal outcomes and larger high-quality observational studies are needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of the Pan American Health Organisation (PAHO), its Board of Directors, or the countries they represent., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hypothesis: A water jet penetrating into a water pool produces air entrainment and bubbles that rise to the surface and disintegrate. A similar scenario can be expected when a granular jet enters into water. This phenomenon is common in natural and industrial processes but remains so far unexplored., Experiments: A collimated jet of monodisperse silica beads was poured into water and the process was filmed with a high-speed camera. The grain size, jet impact velocity, and the liquid physical properties were systematically varied., Findings: For grains of ~50-300μm in diameter, the granular jet deforms the air-water interface, penetrates the pool and produces air entrainment. Most of the entrained air is contained in the interstitial space of the jet, and its volume is linearly proportional to the volume of grains. The bubbles formed in this process are covered by a layer of grains attached to the bubble air-water interface due to capillary-induced cohesion. These "granular bubbles" are stable over time because the granular shell prevents coalescence and keeps the air encapsulated, either if the bubbles rise to the surface or sink to the bottom of the pool, which is determined by the competition of the buoyancy and the weight of the assembly., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population., Objectives: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN., Patients/methods: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds., Results: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04)., Conclusions: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN., (© 2020 Blackwell Verlag GmbH.)

Background: Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity., Aim: To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile., Method: Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains., Results: 95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to β lactams. As expected, there were not non-susceptible strains to vancomycin., Discussion: VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to β lactams is an issue that requires strict epidemiological surveillance in this population.

The diagnosis of American tegumentary leishmaniasis (ATL) still requires the design of more effective tools. Leishmania (Viannia) braziliensis is the causal agent of the 90% of Argentinean ATL cases. Considering the current knowledge, an ELISA based crude antigen (CA) for the diagnosis was designed. Ninety-nine subjects diagnosed as ATL, 27 as no-ATL, and 84 donors from non-ATL-endemic areas were included in this study. The current ATL diagnosis was based four techniques, dermal smear microscopic examination (parasitological test), PCR, Leishmanin skin test, and clinical records. We obtained CA extracts from promastigotes and amastigotes from macrophage cultures of different zymodemes of endemic Leishmania species circulating in the study area. Crude antigens from the 'local' main zymodeme of L. (V.) braziliensis showed the highest reactivity against anti-Leishmania antibodies compared to the other included species. The CA of amastigotes of this zymodeme was 3.4 fold more reactive than promastigotes one. Moreover, amastigote-membrane CA (MCA) were 3.6 fold more reactive than the soluble antigens. The MCA-ELISA reached a sensitivity and specificity of 98% (CI = 94.7%-100%) and 63.6% (53.9-73.1), respectively. When anti-Trypanosoma cruzi reactive sera were excluded, the specificity reached 98.4% (94.4-100), while the sensitivity was similar, with a positive predictive value (PV) of 98.6% (94.6-100) and negative PV of 96.3% (91.6-100). The performance of the MCA-ELISA results strongly contribute to the final diagnostic decision, since a non-reactive serological result almost discards the suspected ATL, because of its high negative PV. The developed MCA-ELISA showed a high diagnostic performance, which makes it a good candidate for ATL diagnosis, for seroprevalence studies, or for monitoring treatments efficacy., Competing Interests: The authors have declared that no competing interests exist.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (μg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 μg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.

Background: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain., Methods: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of β-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed., Results: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively., Conclusions: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM., (© 2019 John Wiley & Sons Ltd.)

Congenital adrenal hyperplasia (CAH) is a group of rare orphan disorders caused by mutations in seven different enzymes that impair cortisol biosynthesis. The 17α-hydroxylase deficiency (17OHD) is one of the less common forms of CAH, corresponding to approximately 1% of the cases, with an estimated annual incidence of 1 in 50,000 newborns. Cases description - two phenotypically female Ecuadorian sisters, both with primary amenorrhea, absence of secondary sexual characteristics, and osteoporosis. High blood pressure was present in the older sister. Hypergonadotropic hypogonadism profile was observed: decreased cortisol and dehydroepiandrosterone sulfate (DHEAS), increased adrenocorticotropic hormone (ACTH) and normal levels of 17-hydroxyprogesterone, extremely high deoxycorticosterone (DOC) levels, and a tomography showed bilateral adrenal hyperplasia in both sisters. Consanguinity was evident in their ancestors. Furthermore, in the exon 7, the variant c.1216T > C, p.Trp406Arg was detected in homozygosis in the CYP17A1 gene of both sisters. We report a homozygous missense mutation in the CYP17A1 gene causing 17OHD in two sisters from Loja, Ecuador. According to the authors, this is the first time such deficiency and mutation are described in two members of the same family in Ecuador.

Studies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most widely spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here, we explore the genetic structure of 176 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, including a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long-distance genetic connections between speakers of the same language family suggest that indigenous languages here were spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including understudied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional-scale analysis., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The use of biological therapies has meant a great improvement in the management of several conditions like autoimmune, neoplastic or others diseases. Although its use has implied significant improvements in the prognosis of these diseases, it is not exempt from complications: infectious diseases as one of them. The objective of this consensus was to evaluate, from an infectious viewpoint, the safeness of the most frequently used biological therapies and give recommendations for the prevention of infections in patients treated with these drugs. These recommendations were based on the highest quality evidence available for the selected biologics. The consensus counts of two manuscripts. This first part details the risks of developing infectious complications depending on the type of biological used for a certain pathology. This evaluation included a broad search in MEDLINE and Epistemonikos of systematic reviews and meta-analyzes of controlled clinical trials and casecontrol examining post-treatment infections with anti-TNF alpha, anti-CD20, anti-CD52, CTLA4-Ig and anti-integrins. The research was complemented by a review of: multicentre cohorts of biological users, the MMWR of the CDC, Atlanta, U.S.A., and national registers and scientific societies in which infectious complications derived from the use of biological therapies were mentioned.

The knowledge of biogeochemical mechanisms involved in soil organic carbon (SOC) storage is crucial to control its release to the atmosphere. In particular, the chemical composition of soil organic matter (SOM) plays an important role in the performance of the C storage and resilience in soils. The structural information provided by infrared spectroscopy (IR) of soil humic acid (HA) was used in the assessment of the C storage potential of 35 Spanish soils. Partial least squares (PLS) regression using the intensities of the points of the IR spectra of the HAs (4000-400 cm -1 ) as descriptors shows that a relationship exists between IR spectral pattern and the SOC content. This was also the case for E4 (humification index based on HA optical density at 465 nm). In addition, the chemical characteristics of the HAs correlated with the SOC levels were identified from digital data treatments of the IR spectra. Additional application of principal component analysis (PCA) and multidimensional scaling (MDS) suggested that bands assigned to carboxyl and amide structures were characteristic in HAs from soils with low C content, whereas HA spectra from soils with high C levels showed a conspicuous band pattern suggesting structural units of lignin from slightly transformed plant residues. The spectral profiles were analyzed in detail by an approach based on digital subtraction of IR spectra obtained by averaging those from HAs extracted from soils in the upper and lower quartiles of the SOC distribution. The results showed that significant relationships exist between the molecular composition of HAs and SOC levels and E4 values in a way in which aromatic, carboxyl and amide groups were predominant in HAs from soils with low SOC content, whereas lignin-derived structures were more characteristic of HAs from soils with high SOC content., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The use of biological therapies has meant a great improvement in the management of several conditions like autoimmune, neoplastic or others diseases. Although its use has implied significant improvements in the prognosis of these diseases, it is not exempt from complications: infectious diseases as one of them. The objective of this consensus was to evaluate, from an infectious viewpoint, the safeness of the most frequently used biological therapies and give recommendations for the prevention of infections in patients treated with these drugs. These recommendations were based on the highest quality evidence available for the selected biologics. The consensus counts of 2 manuscripts. This second part is a guideline that details these recommendations through screening strategies, prophylactic therapies and vaccines indications for bacterial, mycobacterial, viral, fungal and parasitic infections, both for adults and children.

This manuscript includes the antiinfective therapeutic resources for immunocompromised patients under chemotherapy by cancer or hematopoietic stem cells transplant (HSCT) receptors. The document presents the antimicrobial therapy indicated in the most prevalent clinical situations in this population and the primary and alternative therapy for some specific microorganisms. The clinical situations included in the analysis are: febrile neutropenia without focus, sepsis, infections of the central nervous system, pneumonia, skin and soft tissue infections, neutropenic enterocolitis and urinary tract infection. The therapeutic resources, recommended doses and special precautions for the use of antimicrobial recommended in bacterial, viral, fungal and parasitic infections in this population are described, including the measurement of plasma concentrations of certain drugs in specific situations.

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes severe economic losses. The disease is characterized by a vesicular condition and it cannot be differentiated from other vesicular diseases. Therefore, laboratory confirmation of any suspected FMD case is compulsory. Despite viral isolation in cell cultures has been considered for many years as the gold standard for FMD diagnosis, the advantages of real-time reverse transcription polymerase chain reaction (rRT-PCR) technology have motivated its use directly in clinical specimens for FMD diagnosis. The current work was aimed to develop and validate a molecular multi-check strategy using rRT-PCR (mMulti-rRT-PCR) based on SYBR-Green I for pan/foot-and-mouth disease virus (pan/FMDV) diagnosis. From in silico approaches, different primer pairs previously reported were selected and modified to reduce the likelihood of viral escape as well as potential failures in the pan/FMDV detection. The analytical parameters were evaluated using a high number of representative viral strains. The repeatability of the assay and its performance on field samples were also assessed. The mMulti-rRT-PCR was able to detect emergent FMDV strains that circulated in South America between the years 2006-2010 and on which the single rRT-PCRs failed when they were applied independently. The results obtained here showed that the proposed system is an accurate and rapid diagnosis method for sensitive and specific detection of FMDV. Thus, a validated mMulti-rRT-PCR assay based on SYBR-Green I detection coupled to melting curves resolution for pan/FMDV diagnosis on clinical samples is proposed. This study also highlights the need to incorporate the multi-target detection principle in the diagnosis of highly variable agents, specially, of those listed by OIE like FMDV.

Objective: To determine the association between surgical and postoperative outcomes as well as cancer follow-up of patients who underwent radical prostatectomy according to body mass index (BMI)., Methods: An analytical observational study with retrospective data collection was conducted. We reviewed the medical records of all the patients who underwent radical prostatectomy between the years 2012-2014. The analysis of the data included a bivariate model to study the associations between BMI and the surgical procedure, its complications, oncologic outcomes and cancer follow-up. Then, we used multivariate logistic regression analysis to determine if there was an independent association between oncologic outcomes and BMI; the model was adjusted by age, hypertension and diabetes mellitus., Results: 272 patients underwent radical prostatectomy: 98 (36.0%) had normal BMI, 142 (52.2%) were overweight and 32 (11.8%) were obese. The median age was 61 interquartile range (IQR=56-66) years old. There were no statistically significant differences in the preoperative and postoperative outcomes according to BMI. The obese patients had longer operative time (176 minutes, IQR=165.0-195.5) nonetheless, the difference was not statistically significant (p=0.18). There were no complications during the procedure (rectal, vascular or obturator nerve injury). The multivariate analysis showed that age, hypertension and diabetes mellitus were not effect modifiers., Conclusions: Our study suggests that there are no differences between surgical and postoperative outcomes according to BMI. This study represents a starting point for future research in our population to determine the impact of the BMI on prostate cancer and its management.

Background: Despite widespread utilization of influenza vaccines, effectiveness (VE) has not been routinely measured in Latin America., Methods: We used a case test-negative control design to estimate trivalent inactivated influenza VE against laboratory-confirmed influenza among hospitalized children aged 6months-5years and adults aged ≥60years which are age-groups targeted for vaccination. We sought persons with severe acute respiratory infections (SARI), hospitalized at 71 sentinel hospitals in Argentina, Brazil, Chile, Colombia, Costa Rica, El Salvador, Honduras, Panama, and Paraguay during January-December 2013. Cases had an influenza virus infection confirmed by real-time reverse transcription PCR (rRT-PCR); controls had a negative rRT-PCR result for influenza viruses. We used a two-stage random effects model to estimate pooled VE per target age-group, adjusting for the month of illness onset, age and preexisting medical conditions., Results: We identified 2620 SARI patients across sites: 246 influenza cases and 720 influenza-negative controls aged ≤5years and 448 cases and 1206 controls aged ≥60years. The most commonly identified subtype among participants (48%) was the influenza A(H1N1)pdm09 virus followed by influenza A(H3N2) (34%) and influenza B (18%) viruses. Among children, the adjusted VE of full vaccination (one dose for previously vaccinated or two if vaccine naïve) against any influenza virus SARI was 47% (95% confidence interval [CI]: 14-71%); VE was 58% (95% CI: 16-79%) against influenza A(H1N1)pdm09, and 65% (95% CI: -9; 89%) against influenza A(H3N2) viruses associated SARI. Crude VE of full vaccination against influenza B viruses associated SARI among children was 3% (95% CI: -150; 63). Among adults aged ≥60years, adjusted VE against any influenza SARI was 48% (95% CI: 34-60%); VE was 54% (95% CI: 37-69%) against influenza A(H1N1)pdm09, 43% (95% CI: 18-61%) against influenza A(H3N2) and 34% (95% CI: -4; 58%) against B viruses associated SARI., Conclusion: Influenza vaccine provided moderate protection against severe influenza illness among fully vaccinated young children and older adults, supporting current vaccination strategies., (Copyright © 2017. Published by Elsevier Ltd.)

The aim of this study was to evaluate the stability of levodopa liposomes co-loaded with three different antioxidants (curcumin, ascorbic acid, and superoxide dismutase (SOD)). For this purpose, multilamellar liposomes were prepared. Curcumin was added into the lipid bilayer while ascorbic acid and SOD were placed into the aqueous phase. The influence of preparation technique and surface charge were also investigated. Vesicles were characterised and free radical scavenging potential was determined. From stability study, ascorbic acid showed better stabilising effect. These co-loaded liposomes also exhibited potential radical scavenging activity where ascorbic acid played a key role. From the study of different preparation techniques and charge, we concluded that cationic liposomes made by Thin Layer Evaporation following extrusion offered the best physicochemical and stability properties. A dual mechanism of these liposomes implies the chemical stabilisation of levodopa (dose reduction) and the antioxidant effect, with a preventive effect on Parkinson's disease.

Background: Microorganisms isolated from blood cultures (BC) in patients with febrile neutropenia (NF) vary over time, requiring systematic monitoring to guide appropriate empirical therapy., Aim: To identify microorganisms isolated from BC and their antimicrobial resistance profile in children with cancer and high risk NF., Method: Prospective, multicenter study. The analysis included episodes of high-risk FN with positive BC in children under 18 years of age treated in five hospitals in Santiago, Chile, 2012-2015., Results: A total of 206 microorganisms were analyzed in 185 episodes of high-risk FN. The main isolates were Gram negative bacilli (46.6%) and Gram positive cocci (45.1%) and the most frequent microorganisms were Escherichia coli (22.8%), coagulase negative Staphylococcus (18.0%) and Klebsiella spp. (16.5%). Escherichia coli and Klebsiella spp showed 4.2% and 67.6% resistance to third generation cephalosporins (cefotaxime/ceftriaxone), 10.6% and 40.6% resistance to fluoroquinolones (ciprofloxacin) and 2.1% and 26.5% to amikacin, respectively. Coagulase negative Staphylococcus and Staphylococcus aureus had 86.4% and 22.2% resistance to oxacillin, Streptococcus viridans group had 71% resistance to penicillin., Discussion: This study updates the etiology and resistance profile of microorganisms isolated in BC from children with cancer and high risk FN, an essential tool for the adequate management of these patients.

This work was aimed at determining the feasibility of artificial neural networks (ANN) by implementing backpropagation algorithms with default settings to generate better predictive models than multiple linear regression (MLR) analysis. The study was hypothesized on timolol-loaded liposomes. As tutorial data for ANN, causal factors were used, which were fed into the computer program. The number of training cycles has been identified in order to optimize the performance of the ANN. The optimization was performed by minimizing the error between the predicted and real response values in the training step. The results showed that training was stopped at 10 000 training cycles with 80% of the pattern values, because at this point the ANN generalizes better. Minimum validation error was achieved at 12 hidden neurons in a single layer. MLR has great prediction ability, with errors between predicted and real values lower than 1% in some of the parameters evaluated. Thus, the performance of this model was compared to that of the MLR using a factorial design. Optimal formulations were identified by minimizing the distance among measured and theoretical parameters, by estimating the prediction errors. Results indicate that the ANN shows much better predictive ability than the MLR model. These findings demonstrate the increased efficiency of the combination of ANN and design of experiments, compared to the conventional MLR modeling techniques.