Efficiency and comparability of using new evidence platforms for updating recommendations: Experience with a type-2 diabetes guideline in Colombia.

Introduction: Updating recommendations for guidelines requires a comprehensive and efficient literature search. Although new information platforms are available for developing groups, their relative contributions to this purpose remain uncertain. Methods: As part of a review/update of eight selected evidence-based recommendationsfor type 2 diabetes, we evaluated the following five literature search approaches (targeting systematic reviews, using predetermined criteria): PubMed for MEDLINE, Epistemonikos database basic search, Epistemonikos database using a structured search strategy, Living overview of evidence (L.OVE) platform, and TRIP database. Three reviewers independently classified the retrieved references as definitely eligible, probably eligible, or not eligible. Those falling in the same "definitely" categories for all reviewers were labelled as "true" positives/negatives. The rest went to re-assessment and if found eligible/not eligible by consensus became "false" negatives/positives, respectively. We described the yield for each approach and computed "diagnostic accuracy" measures and agreement statistics. Results: Altogether, the five approaches identified 318 to 505 references for the eight recommendations, from which reviewers considered 4.2 to 9.4% eligible after the two rounds. While Pubmed outperformed the other approaches (diagnostic odds ratio 12.5 versus 2.6 to 5.3), no single search approach returned eligible references for all recommendations. Individually, searches found up to 40% of all eligible references (n = 71), and no combination of any three approaches could find over 80% of them. Kappa statistics for retrieval between searches were very poor (9 out of 10 paired comparisons did not surpass the chance-expected agreement). Conclusion: Among the information platforms assessed, PubMed appeared to be more efficient in updating this set of recommendations. However, the very poor agreement among search approaches in the reference yield demands that developing groups add information from several (probably more than three) sources for this purpose. Further research is needed to replicate our findings and enhance our understanding of how to efficiently update recommendations.

Introducción: La actualización de recomendaciones de las guías de práctica clínica requiere búsquedas bibliográficas exhaustivas y eficientes. Aunque están disponibles nuevas plataformas de información para grupos desarrolladores, su contribución a este propósito sigue siendo incierta. Métodos: Como parte de una revisión/actualización de 8 recomendaciones basadas en evidencia seleccionadas sobre diabetes tipo 2, evaluamos las siguientes cinco aproximaciones de búsqueda bibliográfica (dirigidas a revisiones sistemáticas, utilizando criterios predeterminados): PubMed para MEDLINE; Epistemonikos utilizando una búsqueda básica; Epistemonikos utilizando una estrategia de búsqueda estructurada; plataforma (L.OVE) y TRIP . Tres revisores clasificaron de forma independiente las referencias recuperadas como definitivamente o probablemente elegibles/no elegibles. Aquellas clasificadas en las mismas categorías "definitivas" para todos los revisores, se etiquetaron como "verdaderas" positivas/negativas. El resto se sometieron a una nueva evaluación y, si se consideraban por consenso elegibles/no elegibles, se convirtieron en "falsos" negativos/positivos, respectivamente. Describimos el rendimiento de cada aproximación, junto a sus medidas de "precisión diagnóstica" y las estadísticas de acuerdo. Resultados: En conjunto, las cinco aproximaciones identificaron 318-505 referencias para las 8 recomendaciones, de las cuales los revisores consideraron elegibles el 4,2 a 9,4% tras las dos rondas. Mientras que Pubmed superó a las otras aproximaciones (odds ratio de diagnóstico 12,5 versus 2,6 a 53), ninguna aproximación de búsqueda identificó por sí misma referencias elegibles para todas las recomendaciones. Individualmente, las búsquedas identificaron hasta el 40% de todas las referencias elegibles (n=71), y ninguna combinación de cualquiera de los tres enfoques pudo identificar más del 80% de ellas. Las estadísticas Kappa para la recuperación entre búsquedas fueron muy pobres (9 de cada 10 comparaciones pareadas no superaron el acuerdo esperado por azar). Conclusiones: Entre las plataformas de información evaluadas, Pubmed parece ser la más eficiente para actualizar este conjunto de recomendaciones. Sin embargo, la escasa concordancia en el rendimiento de las referencias exige que los grupos desarrolladores incorporen información de varias fuentes (probablemente más de tres) para este fin. Es necesario seguir investigando para replicar nuestros hallazgos y mejorar nuestra comprensión de cómo actualizar recomendaciones de forma eficiente.

Hyperparasitism in bat flies (Diptera: Streblidae): new records and interaction networks in the Neotropics.

Hyperparasitism is defined as the interaction where one parasite is infected by another parasite. In bat flies (Streblidae and Nycteribiidae), both hyperparasites and microparasites (bacteria, viruses, fungi, and arthropods such as mites) have been documented. Fungi belonging to the order Laboulbeniales are microscopic parasites of a wide diversity of arthropod hosts. Three genera exclusively target bat flies: Arthrorhynchus, which parasitizes species within Nycteribiidae in the Eastern Hemisphere, while genus Gloeandromyces and Nycteromyces parasitize Streblidae in the Western Hemisphere. Among the hyperparasitic arthropods, mites of family Neothrombidiidae, particularly the monospecific genus Monunguis, are known to parasitize bat flies. Here we present the first records of the hyperparasites Monunguis streblida and Gloeandromyces pageanus f. polymorphus parasitizing Streblidae bat flies in Colombia and a summary of these hyperparasitic interactions in the Neotropics. We detected fungi and mites parasitizing bat flies that were collected in the Magdalena River Basin, Colombia, in field expeditions in 2018, 2022, and 2023. We identified 17 bat flies and two species of hyperparasites, specifically M. streblida and the fungi Gloeandromyces. Our search for reports of these interactions in the Neotropics revealed that seven species of Trichobius (Streblidae) are parasitized by M. streblida, whereas Paratrichobius longicrus (Streblidae) is parasitized by Gloeandromyces pageanus f. polymorphus. These interactions have been reported in 11 countries, but our records are the first of M. streblida and Laboulbeniales fungi parasitizing bat flies in Colombia. So far, a total of 14 species of fungi and one species of mite have been associated with 19 species of bat flies, which in turn, are linked to 15 species of Neotropical bats.

Improving the ability to discriminate medical multiple-choice questions through the analysis of the competitive examination to assign residency positions in Spain.

INTRODUCTION: Psychometrics plays a vital role in evaluating educational research, including the analysis of multiple-choice exams. This study aims to improve the discriminatory ability of the "Médico Interno Residente" (MIR) medical exam in Spain, used to rank candidates for specialized healthcare training, through psychometric analysis. METHODS: We analyzed 2,890 MIR exam questions from 2009 to 2021 (totaling 147,214 exams), categorizing them based on methodology and response type. Evaluation employed classical test theory and item response theory (IRT). Classical test theory determined difficulty and discrimination indices, while IRT assessed the relationship between knowledge levels and question performance. RESULTS: Question distribution varied across categories and years. Frequently addressed knowledge areas included various medical specialties. Non-image-associated clinical cases were the easiest, while case-based clinical questions exhibited the highest discriminatory capacity, differing significantly from image-based case or negative questions. High-quality questions without images had longer stems but shorter answer choices. Adding images reduced discriminatory power and question difficulty, with image-based questions being easier. Clinical cases with images had shorter stems and longer answer choices. CONCLUSIONS: For improved exam performance, we recommend using a clinical case format followed by direct short-answer questions. Questions should be of low difficulty, providing clear and specific answers based on scientific evidence and avoiding ambiguity. Typical clinical cases with key characteristic features should be presented, excluding uncertain boundaries of medical knowledge. Questions should have lengthy stems and concise answer choices, minimizing speculation. If images are used, they should be typical, clear, consistent with the exam, and presented within clinical cases using clinical semiotics and propaedeutics.

Erratum: Survey of Conductive Polymers for the Fabrication of Conformation Switching Nucleic Acid-Based Electrochemical Biosensors.

[This corrects the article DOI: 10.1021/acsapm.3c02206.].

Enhancing Trypanosomatid Identification and Genotyping with Oxford Nanopore Sequencing: Development and Validation of an 18S rRNA Amplicon-Based Method.

Trypanosomatids, including Trypanosoma and Leishmania species, present significant medical and veterinary challenges, causing substantial economic losses, health complications, and even fatalities. Diagnosing and genotyping these species and their genotypes is often complex, involving multiple steps. This study aimed to develop an amplicon-based sequencing (ABS) method using Oxford Nanopore long-read sequencing to enhance Trypanosomatid detection and genotyping. The 18S rDNA gene was targeted for its inter-species conservation. The Trypanosomatid-ABS method effectively distinguished between 11 Trypanosoma species (including Trypanosoma evansi, Trypanosoma theileri, Trypanosoma vivax, and Trypanosoma rangeli) and 6 Trypanosoma cruzi discrete typing units (TcI to TcVI and TcBat), showing strong concordance with conventional methods (κ index of 0.729, P < 0.001). It detected co-infections between Trypanosomatid genera and T. cruzi, with a limit of detection of one parasite per mL. The method was successfully applied to human, animal, and triatomine samples. Notably, TcI predominated in chronic Chagas samples, whereas TcII and TcIV were found in the acute stage. Triatomine vectors exhibited diverse Trypanosomatid infections, with Triatoma dimidiata mainly infected with TcI and occasional TcBat co-infections, and Rhodnius prolixus showing TcI and TcII infections, along with T. rangeli co-infections and mixed TcII infections. Animals were infected with T. vivax, T. theileri, and T. evansi. The ABS method's high resolution, sensitivity, and accuracy make it a valuable tool for understanding Trypanosomatid dynamics, enhancing disease control strategies, and enabling targeted interventions.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

BACKGROUND: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. METHODS: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FINDINGS: From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69-2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61-2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04-0·95; p=0·044). INTERPRETATION: Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FUNDING: European Community's 7th Framework Programme.

One-year Outcomes after Discharge from Noncardiac Surgery and Association between Predischarge Complications and Death after Discharge: Analysis of the VISION Prospective Cohort Study.

BACKGROUND: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery. METHODS: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis. RESULTS: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr). CONCLUSIONS: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge.

Knowledge of Vaccination Against Influenza and Pneumococcus in Patients with Chronic Obstructive Pulmonary Disease in an Integrated Care Program.

Purpose: To compare the level of knowledge in vaccination against influenza and pneumococcus of patients with chronic obstructive pulmonary disease (COPD) who are managed in an Integrated Care Program (ICP) with those who receive usual care (UC). Methods: A telephone survey of patients diagnosed with COPD registered in public care networks or private institutions was done. A descriptive and comparative analysis of the characteristics of the ICP and UC groups was carried out. The relationship between belonging to an ICP and the level of knowledge about vaccination was evaluated using Propensity Score Matching (PSM) and multivariate logistic and ordinal regression models. Results: Of 674 study participants, 27.2% were from the ICP group. ICP patients were older, more frequently men, from a higher socioeconomic stratum and a higher educational level (p<0.05). 75.5% of the patients in the ICP group had a high level of vaccination knowledge compared to 42.7% in the UC group (p<0.001). In the multivariate analysis, adjusting for sociodemographic variables, years of COPD diagnosis, and comorbidities, belonging to the ICP was associated with a higher probability of answering questions about vaccination correctly and having a high level of knowledge (OR 3.397, IC 95% 2.058-5.608, p<0.001). Conclusion: Patients with COPD managed in an ICP have a higher level of knowledge in vaccination against influenza and pneumococcus, compared to patients in usual care.

Reporting of blood pressure levels and self-monitoring practices: a survey among outpatients diagnosed with hypertension in Bogotá, Colombia.

BACKGROUND: Routine blood pressure (BP) self-monitoring is recommended for patients already diagnosed with hypertension. How often these patients can report their BP levels is unknown, particularly in low-and-middle income countries. METHODS: We surveyed (January 2021 to May 2022) representative samples of patients with established diagnosis of hypertension from 3 health care networks (involving 74 outpatient clinics) and 2 university hospitals in Bogotá, Colombia. Trained health care professionals conducted a telephone survey including questions on demographics, medical history, and general understanding about hypertension and its potential complications. The outcome variables were the self-report of participant's BP levels (primary) and monitoring practices among participants. RESULTS: Out of 2609 consecutively contacted patients sampled from institutional records, 2323 were invited and 1566 (mean age 66.5, SD = 12.1 years, 74.4% females, 64.0% living low socio-economic strata) gave consent to participate. While 66% of participants had over 5 years of diagnosis, 39.5% had most (≥ 60%) of their follow-up visits with the same doctor. Overall, 645 (41.5%, 95%CI 39.1 -43.9) participants reported their BP levels. This proportion was independent of time from diagnosis, but higher among those of younger age, living in higher socio-economic strata, having more years of education and using more information technologies. Also, more patients reported their BP levels if seen ≥ 60% of the times by the same physician (43.4% Vs. 36.7%). Those reporting closer BP self-monitoring more often used electronic devices, received 2 + medications, and had better knowledge about hypertension. CONCLUSION: A minority of hypertensive patients seen in Bogotá were aware of their own BP levels. Those in such capacity were in a better social position, more often seen by the same doctor, knew their condition better and handled more complex treatments. Hypertensive patients from Bogotá may benefit from a more continuous medical care, patient education programs and promoting BP home monitoring.

Deep serological profiling of the Trypanosoma cruzi TSSA antigen reveals different epitopes and modes of recognition by Chagas disease patients.

BACKGROUND: Trypanosoma cruzi, the agent of Chagas disease, displays a highly structured population, with multiple strains that can be grouped into 6-7 evolutionary lineages showing variable eco-epidemiological traits and likely also distinct disease-associated features. Previous works have shown that antibody responses to 'isoforms' of the polymorphic parasite antigen TSSA enable robust and sensitive identification of the infecting strain with near lineage-level resolution. To optimize the serotyping performance of this molecule, we herein used a combination of immunosignaturing approaches based on peptide microarrays and serum samples from Chagas disease patients to establish a deep linear B-cell epitope profiling of TSSA. METHODS/PRINCIPLE FINDINGS: Our assays revealed variations in the seroprevalence of TSSA isoforms among Chagas disease populations from different settings, hence strongly supporting the differential distribution of parasite lineages in domestic cycles across the Americas. Alanine scanning mutagenesis and the use of peptides of different lengths allowed us to identify key residues involved in antibody pairing and the presence of three discrete B-cell linear epitopes in TSSAII, the isoform with highest seroprevalence in human infections. Comprehensive screening of parasite genomic repositories led to the discovery of 9 novel T. cruzi TSSA variants and one TSSA sequence from the phylogenetically related bat parasite T. cruzi marinkellei. Further residue permutation analyses enabled the identification of diagnostically relevant or non-relevant substitutions among TSSA natural polymorphisms. Interestingly, T. cruzi marinkellei TSSA displayed specific serorecognition by one chronic Chagas disease patient from Colombia, which warrant further investigations on the diagnostic impact of such atypical TSSA. CONCLUSIONS/SIGNIFICANCE: Overall, our findings shed new light into TSSA evolution, epitope landscape and modes of recognition by Chagas disease patients; and have practical implications for the design and/or evaluation of T. cruzi serotyping strategies.

Endovascular thrombectomy first-pass reperfusion and ancillary device placement.

BACKGROUND: Recent randomized trials have demonstrated the efficacy of mechanical thrombectomy in treating acute ischemic stroke, however, further research is required to optimize this technique. We aimed to evaluate the impact of guide catheter position and clot crossing on revascularization rates using A Direct Aspiration First Pass Technique (ADAPT). METHODS: Data were collected between January 2018 and August 2019 as part of the Spanish ADAPT Registry on ACE catheters (SARA), a multicenter observational study assessing real-world thrombectomy outcomes. Demographic, clinical, and angiographic data were collected. Subgroup analyses assessed the relationship between guide catheter/microguidewire position and modified Trombolysis in Cerebral Infarction (mTICI) scores. First pass effect (FPE) was defined as mTICI 3 after single pass of the device. RESULTS: From a total of 589 patients, 80.8% underwent frontline aspiration thrombectomy. The median score on the National Institutes of Health Stroke Scale (NIHSS) was 16.0. After adjusting for confounders, the likelihood of achieving FPE (adjusted Odds Ratio (aOR), 0.587; 95% confidence interval (CI), 0.38 to 0.92; p=0.0194) were higher among patients with more distal petrocavernous placement of guide catheter. The likelihood of achieving FPE (aOR, 0.592; 95% CI, 0.39 to 0.90; p=0.0138) and final angiogram complete reperfusion (aOR, 0.465; 95% CI, 0.30 to 0.73; p=0.0008) were higher among patients without microguidewire crossing the clot. No difference was noted for time from arterial puncture to reperfusion in any study group. At the 90-day follow-up, the mortality rate was 9.2% and 65.8% of patients across the entire study cohort were functionally independent (modified Rankin Scale (mRS) 0-2). CONCLUSIONS: Petrocavernous guide catheter placement improved first-pass revascularization. Crossing the occlusion with a microguidewire lowered the likelihood of achieving FPE and complete reperfusion after final angiogram.

The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas.

During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of serological biomarkers.

Endothelial and Glycocalyx Biomarkers in Children With Sepsis After One Bolus of Unbalanced or Balanced Crystalloids.

OBJECTIVES: To assess the disruption of endothelial glycocalyx integrity in children with sepsis receiving fluid resuscitation with either balanced or unbalanced crystalloids. The primary outcome was endothelial glycocalyx disruption (using perfused boundary region >2 µm on sublingual video microscopy and syndecan-1 greater than 80 mg/dL) according to the type of crystalloid. The secondary outcomes were increased vascular permeability (using angiopoietin-2 level), apoptosis (using annexin A5 level), and associated clinical changes. DESIGN: A single-center prospective cohort study from January to December 2021. SETTING: Twelve medical-surgical PICU beds at a university hospital. PATIENTS: Children with sepsis/septic shock before and after receiving fluid resuscitation with crystalloids for hemodynamic instability. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We included 106 patients (3.9 yr [interquartile range, 0.60-13.10 yr]); 58 of 106 (55%) received boluses of unbalanced crystalloid. This group had greater odds of endothelial glycocalyx degradation (84.5% vs 60.4%; adjusted odds ratio, 3.78; 95% CI, 1.49-9.58; p < 0.01) 6 hours after fluid administration, which correlated with increased angiopoietin-2 (rho = 0.4; p < 0.05) and elevated annexin A5 ( p = 0.04). This group also had greater odds of metabolic acidosis associated with elevated syndecan-1 (odds ratio [OR], 4.88; 95% CI, 1.23-28.08) and acute kidney injury (OR, 1.7; 95% CI, 1.12-3.18) associated with endothelial glycocalyx damage. The perfused boundary region returned to baseline 24 hours after receiving the crystalloid boluses. CONCLUSIONS: Children with sepsis, particularly those who receive unbalanced crystalloid solutions during resuscitation, show loss and worsening of endothelial glycocalyx. The abnormality peaks at around 6 hours after fluid administration and is associated with greater odds of metabolic acidosis and acute kidney injury.

Adherence to evidence-based recommendations for chronic noncommunicable diseases: a multicenter cross-sectional study of Bogotá physicians / Adherencia a recomendaciones basadas en evidencia para enfermedades crónicas no transmisibles: estudio de corte transversal multicéntrico en médicos de Bogotá / Adesão às recomendações baseadas em evidências para doenças crônicas não transmissíveis: estudo transversal multicêntrico em médicos de Bogotá

Introduction. The management of patients with chronic noncommunicable diseases, when it follows evidence-based recommendations, improves clinical outcomes and health costs. Despite its importance, little is known about adherence to guidelines and the processes for its monitoring in our environment. The objective of this study was to report the applicability and adherence to a selection of recommendations from clinical practice guidelines for noncommunicable chronic diseases by doctors in Bogotá. Methods. This was a cross-sectional study, the baseline of a cluster experiment that assessed the impact of disseminating recommendations on seven chronic diseases to patients, caregivers, and physicians. A total of 177 physicians from public and private health institutions were invited. Consecutive samples of their medical records were manually reviewed in predefined time ranges (up to 20 patients per physician, with up to two diseases of interest). The proportions of applicability and adherence were calculated according to 40 recommendations. Results. The 177 physicians who participated (out of 266 eligible) were from seven institutions, and 3,747 medical records (21,093 patients/recommendation) were analyzed. The general applicability was 31.9% (95% CI 31.3-32.6%), and it varied considerably by recommendation (range 0.3-100%) and disease (range 10.7-65%). Overall adherence was 42.0% (95% CI 40.8-43.2%), with higher adherence in acute coronary syndrome patients (58.4%) and lower adherence in diabetes mellitus patients (23.7%). Discussion. This is the most up-to-date, exhaustive, and representative measurement of adherence to guideline recommendations by doctors in Bogotá. Conclusions. Adherence to evidence-based recommendations for patients with chronic noncommunicable diseases in Bogotá is poor and highly variable. Keywords: Practice Guideline; Evidence-Based Medicine; Noncommunicable Diseases; Quality of Health Care; Implementation Science; Internal Medicine; Primary Health Care

Introducción. El manejo de pacientes con enfermedades crónicas no transmisibles, cuando se realiza a partir de recomendaciones basadas en la evidencia, mejora los desenlaces clínicos y los costos en salud. Pese a su importancia, poco se conocen la adherencia a las recomendaciones de guías y los procesos para su monitoreo en nuestro medio. El objetivo de este estudio es reportar la aplicabilidad y la adherencia a una selección de recomendaciones de guías de práctica clínica, en enfermedades crónicas no transmisibles, por médicos de Bogotá. Metodología. Estudio de corte MSc.Participaron 177 médicos de instituciones de salud públicas y privadas. Se revisaron manualmente muestras consecutivas de sus historias clínicas en rangos de tiempo predefinidos (meta hasta 20 pacientes por médico, en hasta dos enfermedades de interés). Se calcularon las proporciones de aplicabilidad y adherencia en 40 recomendaciones. Resultados. Participaron 177 médicos (de 266 elegibles), de 7 instituciones, con 3,747 historias clínicas (21,093 pacientes/recomendación) analizadas. La aplicabilidad general fue 31.9% (IC95% 31.3%-32.6%), y varió considerablemente por recomendación (rango 0.3%-100%) y enfermedad (rango 10.7%-65%). La adherencia general fue 42.0% (IC95% 40.8% -43.2%), siendo mayor en síndrome coronario agudo (58.4%) y menor en diabetes mellitus (23.7%). Discusión. Esta es la medición más actualizada, exhaustiva y representativa de la adherencia a las recomendaciones de guías por parte de médicos de Bogotá. Conclusiones. La adherencia a recomendaciones basadas en evidencia, para pacientes con enfermedades crónicas no transmisibles de Bogotá, es deficiente y altamente variable. Palabras clave: Guía de Práctica Clínica; Medicina Basada en la Evidencia; Enfermedades no Transmisibles; Calidad de la Atención de Salud; Ciencia de la Implementación; Medicina Interna; Atención Primaria de Salud

Introdução. O manejo de pacientes com doenças crônicas não transmissíveis, quando realizado com base em recomendações baseadas em evidências, melhora os resultados clínicos e os custos de saúde. Apesar da sua importância, pouco se sabe sobre a adesão às recomendações das diretrizes e os processos para monitorá-la em nosso meio. O objetivo deste estudo é relatar a aplicabilidade e adesão a uma seleção de recomendações das diretrizes de prática clínica, em doenças crônicas não transmissíveis, por médicos em Bogotá. Metodologia. Estudo transversal (linha de base de um experimento cluster que avalia o impacto da divulgação de recomendações sobre sete doenças crônicas a pacientes, cuidadores e médicos). Participaram 177 médicos de instituições de saúde públicas e privadas. Foram revisadas manualmente amostras consecutivas de seus prontuários em intervalos de tempo pré-definidos (alvo de até 20 pacientes por médico, em até duas doenças de interesse). Foram calculadas proporções de aplicabilidade e adesão para 40 recomendações. Resultados. Participaram 177 médicos (de 266 elegíveis), de 7 instituições, com 3,747 prontuários (21,093 pacientes/recomendação) analisados. A aplicabilidade geral foi de 31.9% (IC 95% 31.3%-32.6%) e variou consideravelmente por recomendação (intervalo 0.3%-100%) e doença (intervalo 10.7%-65%). A adesão geral foi de 42.0% (IC 95% 40.8%-43.2%), sendo maior na síndrome coronariana aguda (58.4%) e menor na diabetes mellitus (23.7%). Discussão. Esta é a medição mais atualizada, exaustiva e representativa da adesão às recomendações das diretrizes por médicos em Bogotá. Conclusões. A adesão às recomendações baseadas em evidências para pacientes com doenças crônicas não transmissíveis em Bogotá é fraca e altamente variável. Palavras-chave: Guia de Prática Clínica; Medicina Baseada em Evidências; Doenças não Transmissíveis; Qualidade da Assistência à Saúde; Ciência da Implementação; Medicina Interna; Atenção Primária à Saúde

Biomarkers of Glycocalyx Injury and Endothelial Activation are Associated with Clinical Outcomes in Patients with Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVE: Sepsis is one of the main causes of morbidity and mortality worldwide. Microcirculatory impairment, especially damage to the endothelium and glycocalyx, is often not assessed. The objective of this systematic review and meta-analysis was to summarize the available evidence of the risk of unsatisfactory outcomes in patients with sepsis and elevated glycocalyx injury and endothelial activation biomarkers. DESIGN: A systematic search was carried out on PubMed/MEDLINE, Embase, Cochrane and Google Scholar up to December 31, 2021, including studies in adults and children with sepsis which measured glycocalyx injury and endothelial activation biomarkers within 48 hours of hospital admission. The primary outcome was the risk of mortality from all causes and the secondary outcomes were the risk of developing respiratory failure (RF) and multiple organ dysfunction syndrome (MODS) in patients with elevations of these biomarkers. MEASUREMENTS AND MAIN RESULTS: A total of 17 studies (3,529 patients) were included: 11 evaluated syndecan-1 (n=2,397) and 6 endocan (n=1,132). Syndecan-1 was higher in the group of patients who died than in those who survived [255 ng/mL (IQR: 139-305) vs. 83 ng/mL (IQR:40-111); p=0.014]. Patients with elevated syndecan-1 had a greater risk of death (OR 2.32; 95% CI 1.89, 3.10: p<0.001), MODS (OR 3.3; 95% CI 1.51, 7.25: p=0.003;), or RF (OR 7.53; 95% CI 1.86-30.45: p=0.005). Endocan was higher in patients who died [3.1 ng/mL (IQR 2.3, 3.7) vs. 1.62 ng/mL (IQR 1.2, 5.7); OR 9.53; 95% CI 3.34, 27.3; p<0.001], who had MODS (OR 8.33; 95% CI 2.07, 33.58; p=0.003) and who had RF (OR 9.66; 95% CI 2.26, 43.95; p=0.002). CONCLUSION: Patients with sepsis and abnormal glycocalyx injury and endothelial activation biomarkers have a greater risk of developing respiratory failure, multiple organ failure, and death. Microcirculatory impairment should be routinely evaluated in patients with sepsis, using biomarkers to stratify risk groups.

Direct evidence gap on fixed versus adjusted-dose benznidazole for adults with chronic Chagas disease without cardiomyopathy: Systematic review and individual patient data meta-analysis.

OBJECTIVES: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy. METHODS: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy. RESULTS: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses. CONCLUSIONS: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future. REGISTRATION: The study protocol was registered in PROSPERO (CRD42019120905).

Diversity of an uncommon elastic hypersaline microbial mat along a small-scale transect.

We evaluated the microbial diversity and metabolome profile of an uncommon hypersaline elastic microbial mat from Cuatro Ciénegas Basin (CCB) in the Chihuahuan Desert of Coahuila, México. We collected ten samples on a small scale transect (1.5-m) and described its microbial diversity through NGS-based ITS and 16S rDNA gene sequencing. A very low number of taxa comprised a considerable proportion of the mat and were shared across all sampling points, whereas the rare biosphere was more phylogenetically diverse (Faith's Phylogenetic Diversity (FPD) index) and phylogenetically disperse (using a null model distribution of Phylogenetic Species Clustering (nmdPSC)) than the abundant (high read count) taxa for both analyzed libraries. We also found a distinctive metabolome profile for each sample and were able to tentatively annotate several classes of compounds with relevant biological properties.

Diaphragm impairment in patients admitted for severe COVID-19.

Among patients affected by the virus COVID-19, physicians have observed ventilation disorders. It is relevant to assess neurological involvement, including the role of diaphragmatic function. Its possible impairment could be related to the systemic inflammatory response and disease progression that both typify COVID-19 infection. We distinguished two groups (severe group (SG) and mild group (MG)) according to the severity of respiratory symptomatology. We performed neurophysiological and sonography studies to evaluate the diaphragmatic function. Regarding the sonography variables, we identified statistically significant differences in the right mean diaphragmatic thickness along with the expiration, showing 1.56 mm (SEM: 0.11) in the SG vs 1.92 mm (SEM: 0.19) in the MG (p = 0.042). The contractibility of both hemidiaphragms was 15% lower in the severe group, though this difference is not statistically significant. In our examination of the neurophysiological variables, in the amplitude responses, we observed a greater difference between responses from both phrenic nerves as follows: the raw differences in amplitude were 0.40 µV (SEM: 0.14) in the SG vs 0.35 µV (SEM: 0.19) in the MG and the percentage difference was 25.92% (SEM: 7.22) in the SG vs 16.28% (SEM: 4.38%) in the MG. Although diaphragmatic dysfunction is difficult to detect, our combined functional and morphological approach with phrenic electroneurograms and chest ultrasounds could improve diagnostic sensitivity. We suggest that diaphragmatic dysfunction could play a relevant role in respiratory disturbance in hospitalised patients with severe COVID-19.