Effectiveness and safety of once-weekly semaglutide: findings from the SEMACOL-REAL retrospective multicentric observational study in Colombia.

Introduction: Diabetes stands as one of the leading causes of death worldwide. Glucagon-like peptide-1 receptor agonists rank among the most effective medications for lowering blood glucose and body weight, as well as reducing cardiovascular risk in individuals with diabetes. Observational studies complement experimental evidence in new settings, different populations, and real-world healthcare practices. Methods: A multicentric observational study of adults with type 2 diabetes treated with once-weekly subcutaneous semaglutide in four health centers in Colombia was conducted. The protocol for the present study was not pre-registered. Results: Data from 186 patients were included. Most patients were women (57%) with a mean age of 62.8 ± 12.1 years. One year of once-weekly semaglutide usage was associated with a mean reduction in HbA1C of -1.47% (95% CI -1.76, -1.17), weight loss of -4.23 kg (95% CI -5.34, -3.12), and albumin/creatinine ratio of -18.6 mg/g (95% CI -60.2, -5.9). Approximately half the treated patients achieved a level of HbA1c ≤7% by the end of follow-up. Adverse events were rare and consistent with clinical trial safety profiles. Conclusion: In Colombia, administering semaglutide subcutaneously once a week over a 1-year period led to an average weight loss of 4.2 kg and a decrease of 1.4% in HbA1c.

Epinephrine Dosing Intervals Are Associated With Pediatric In-Hospital Cardiac Arrest Outcomes: A Multicenter Study.

OBJECTIVES: Data to support epinephrine dosing intervals during cardiopulmonary resuscitation (CPR) are conflicting. The objective of this study was to evaluate the association between epinephrine dosing intervals and outcomes. We hypothesized that dosing intervals less than 3 minutes would be associated with improved neurologic survival compared with greater than or equal to 3 minutes. DESIGN: This study is a secondary analysis of The ICU-RESUScitation Project (NCT028374497), a multicenter trial of a quality improvement bundle of physiology-directed CPR training and post-cardiac arrest debriefing. SETTING: Eighteen PICUs and pediatric cardiac ICUs in the United States. PATIENTS: Subjects were 18 years young or younger and 37 weeks old or older corrected gestational age who had an index cardiac arrest. Patients who received less than two doses of epinephrine, received extracorporeal CPR, or had dosing intervals greater than 8 minutes were excluded. INTERVENTIONS: The primary exposure was an epinephrine dosing interval of less than 3 vs. greater than or equal to 3 minutes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was survival to discharge with a favorable neurologic outcome defined as a Pediatric Cerebral Performance Category score of 1-2 or no change from baseline. Regression models evaluated the association between dosing intervals and: 1) survival outcomes and 2) CPR duration. Among 382 patients meeting inclusion and exclusion criteria, median age was 0.9 years (interquartile range 0.3-7.6 yr) and 45% were female. After adjustment for confounders, dosing intervals less than 3 minutes were not associated with survival with favorable neurologic outcome (adjusted relative risk [aRR], 1.10; 95% CI, 0.84-1.46; p = 0.48) but were associated with improved sustained return of spontaneous circulation (ROSC) (aRR, 1.21; 95% CI, 1.07-1.37; p < 0.01) and shorter CPR duration (adjusted effect estimate, -9.5 min; 95% CI, -14.4 to -4.84 min; p < 0.01). CONCLUSIONS: In patients receiving at least two doses of epinephrine, dosing intervals less than 3 minutes were not associated with neurologic outcome but were associated with sustained ROSC and shorter CPR duration.

Comparative study of weekly and three-weekly neoadjuvant carboplatin in triple-negative breast cancer: retrospective analysis in real-world settings.

PURPOSE: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates. METHODS/PATIENTS: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin. RESULTS: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186). CONCLUSIONS: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings.

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5 days) with long-course (≥ 7 days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270).  Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15 months.    PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15 months between short and long-course therapy.

Sequential therapy with topical clobetasol for 14 days followed by hydroquinone versus hydroquinone alone in facial melasma treatment: a randomized, double-blind, controlled clinical trial.

BACKGROUND: Clobetasol has demonstrated remarkable results in treating melasma within a short time frame; however, its use is limited because of the risk of local side effects. To date, there is no controlled trial on sequential clobetasol/hydroquinone for melasma. This study aimed to investigate the tolerability and efficacy of 0.05% clobetasol followed by 4% hydroquinone (CLOB-HQ) in comparison to the isolated use of 4% hydroquinone (HQ). METHODS: A double-blinded, randomized clinical trial involving 50 women with facial melasma was performed. They were directed to apply 0.05% clobetasol every night for 14 days, followed by 4% hydroquinone for 46 days (CLOB-HQ group), or the use of hydroquinone for 60 days (HQ group). Evaluations were carried out at inclusion, and after 14 and 60 days of treatment, measuring modified Melasma Area and Severity Index (mMASI), Melasma Quality of Life scale (MELASQoL), and colorimetry. The Global Aesthetic Improvement Scale (GAIS) was assessed by a blinded evaluator. RESULTS: There was no difference in the main outcomes at D14 and D60 (P > 0.1). For CLOB-HQ, the mean (CI 95%) reduction in mMASI was 13.2% (5.1-21.3%) and 43.1% (32.2-54.0%) at D14 and D60, and for HQ, they were 10.6% (5.9-27.5%) and 44.8% (33.2-52.3%). The MELASQoL, colorimetric luminosity, and GAIS showed a progressive improvement for both groups despite no difference between them. No severe side effects were identified. No cases of telangiectasias, atrophy, or perioral dermatitis were associated with the use of CLOB. CONCLUSION: The sequential CLOB-HQ regimen was safe and well tolerated, even though its efficacy was not different from HQ after 14 or 60 days of treatment. Based on these findings, the use of clobetasol 14 days before hydroquinone is not advisable for the treatment of melasma.

The effect of different levothyroxine administration regimens on thyroid hormone levels: a systematic review, pairwise, and network meta-analysis.

INTRODUCTION: This systematic review aimed to compare the effect of alternative levothyroxine administration regimens on thyroid hormone levels and patient-reported outcomes (PROs) among adults with hypothyroidism. METHODS: We searched PubMed, Embase, CENTRAL, CINAHL, LILACS, SciELO, Scopus, Web of Science, OpenGrey, ProQuest, ClinicalTrials.gov, and ICTRP from inception to May/2023 for randomized controlled trials (RCTs). We assessed the risk of bias with Cochrane Risk of Bias 2.0 tool. We analyzed TSH levels by pairwise and network meta-analyses (NMA). The FT4 levels and PROs were qualitatively assessed. RESULTS: We included 14 RCTs (906 participants) comparing different regimens, as bedtime vs. before breakfast. A total of 12 RCTs were at high risk of bias. Seven RCTs were included in the TSH meta-analysis, where the mean difference (MD) and 95% confidence interval (CI) were as follows: bedtime vs before breakfast (4 RCTs) 0.69 (-1.67-3.04), I2 = 92%, very low certainty evidence; weekly dose vs before breakfast (2 RCTs) 1.68 (0.94-2.41), I2 = 0%, low certainty evidence; and at breakfast vs before breakfast (1 RCT) 0.65 (-1.11-2.41), very low certainty evidence. The NMA showed no evidence of differences in TSH level with different regimens. CONCLUSION: The evidence is insufficient to determine the most effective levothyroxine administration regimen for hypothyroidism. SYSTEMATIC REVIEW REGISTRATION: PROSPERO - CRD42021279375.

Eficacia y seguridad del uso extendido de anticonceptivos orales combinados / Efficacy and safety of extended use of combined oral contraceptives

Los anticonceptivos orales combinados constituyen hoy en día uno de los métodos anticonceptivos más populares a nivel mundial. Su composición consiste en una combinación de análogos de hormonas sexuales femeninas que se administran en bajas dosis diarias, manteniendo constante su concentración sanguínea y evitando de esta forma los cambios en el eje endócrino que estimulan la ovulación. Con el objetivo de recrear los procesos fisiológicos, la mayoría de las formulaciones comprenden un intervalo de 4 a 7 días libres de hormonas en el cual se genera el sangrado por deprivación.A partir de una viñeta clínica en la que una paciente sana desea posponer su hemorragia por deprivación, y tras realizar una búsqueda bibliográfica que prioriza las investigaciones más recientes y de mejor calidad, la autora revisa la evidencia sobre el uso de hormonas sin intervalo libre, especialmente su efectos sobre la eficacia y la incidencia de efectos adversos. (AU)

Nowadays, combined oral contraceptives are one of the most popular contraceptive methods worldwide. Its composition consists of a combination of similar female sex hormones administered in low daily doses, keeping their blood concentration constant and thus avoiding changes in the endocrine axis that stimulate ovulation. In order to recreate physiological processes, most formulations include an interval of 4 to 7 hormone-free days in which withdrawal bleeding occurs.Starting from a clinical vignette in which a healthy patient desires to postpone her withdrawal bleeding, and after conducting a bibliographic search that prioritizes the most recent and best-quality research, the author reviews the evidence about the use of hormones without free interval, especially their effects on efficacy and the incidence of adverse effects. (AU)

Cálculo de los Días de Terapia Antimicrobiana (DOT) en Cuidados Intensivos Pediátricos: una propuesta de metodología basada en el sistema informático de dispensación de medicamentos / Days of Antimicrobial Therapy (DOT) calculation in Pediatric Intensive Care: a methodology proposal based on the electronic records from the pharmacy dispensation system

INTRODUCCIÓN: El método recomendado para la medición de consumo de antimicrobianos (AMB) en pediatría es el cálculo del indicador Días de Terapia estandarizado por ocupación (DOT-std). Sin embargo, en hospitales que no cuentan con fichas electrónicas, obtener el numerador de los días de terapia (DOT) requiere revisión directa de las indicaciones del paciente, dificultando su aplicabilidad. OBJETIVOS: Validar el sistema de registros electrónicos de dispensación de medicamentos desde farmacia como fuente para el cálculo de DOT y DOT-std en la Unidad de Cuidados Intensivos Pediátrica (UCIP). MATERIALES Y MÉTODOS: Se revisaron las prescripciones de AMB desde la ficha clínica (método manual) y se compararon con los registros de dispensación de AMB a la UCIP (método informático) obtenidos del sistema de medicamentos de farmacia. Se evaluó la concordancia entre los DOT obtenidos mediante el Coeficiente de Correlación Intraclase. RESULTADOS: Los AMB más utilizados fueron vancomicina, meropenem y piperacilina/tazobactam. En 9 de 12 AMB se encontró concordancia significativa entre ambos métodos. CONCLUSIONES: Tras un proceso de validación local, los registros del sistema informático de dispensación de medicamentos desde farmacia podrían utilizarse para el cálculo de DOT en pediatría en hospitales que no cuenten con una ficha electrónica que permita su cálculo directo.

BACKGROUND: The recommended indicator for measuring antimicrobial (AMB) consumption in pediatric patients is the Days of Therapy indicator (DOT), which is then standardized by hospital occupancy rates (DOT-std). However, in hospitals that do not have electronic health records, obtaining the DOT requires a direct review of each pharmacological indication, which is not feasible in the long term. AIMS: To validate electronic records from the pharmacy dispensation system as a source for calculating DOT and estimating DOT-std in a Pediatric Intensive Care Unit (PICU). METHODS: AMB prescriptions at the PICU of a university hospital were directly reviewed (manual method) and compared with AMB dispensation records (computer method) obtained from the hospital pharmacy system. The Intraclass Correlation Coefficient was used to evaluate the agreement between the DOT obtained by both methods. RESULTS: The most used AMB were vancomycin, meropenem, and piperacillin/tazobactam. A significant agreement between the DOT obtained by using manual and computer methods was found in 9 of 12 evaluated AMB. CONCLUSIONS: After a local validation process, the electronic records of the pharmacy drug dispensation system could be considered a valid source for calculating DOT in PICUs in hospitals where electronic health records with prescription data are not yet available.

Consultas a urgencia y valores espirométricos tras el reemplazo de salmeterol/fluticasona por budesonida/formoterol en pacientes con asma moderada a grave / Emergency consultations and spirometric values after replacement of salmeterol/fluticasone with budesonide/formoterol in patients with moderate to severe asthma

El asma se caracteriza por su impacto deletéreo que incluye gran coste económico para el sistema de salud. En pacientes con asma mal controlada a pesar del tratamiento, se propone un régimen de mantenimiento con corticoides inhalados y formoterol. El objetivo del presente estudio observacional retrospectivo fue evaluar las modificaciones espirométricas tras el cambio del medicamento controlador en pacientes con asma moderada a severa asistidos en el Hospital Clínico de Magallanes de Punta Arenas, así como también cuantificar la modificación en el número de exacerbaciones graves (consulta a un servicio de urgencia y/u hospitalización por asma). Participaron 61 adultos con asma moderada a severa (mediana de edad: 60 años [rango: 21-87], mujeres: 69,4%; comorbilidad atópica/alérgica: 79%; otras comorbilidades: 46,8%) en los que se cambió el tratamiento con fluticasona/salmeterol 250/25 μg por budesónida/formoterol 160/4,5 μg. No se observaron cambios significativos en los índices espirométricos tras el cambio. Con el tratamiento inicial, el 46,9% presentó ≥ 1 visita a urgencias (total: 50 consultas). Tras el cambio por budesonida/formoterol, el 21% requirió al menos una visita a urgencias (total: 14 consultas; p < 0,01). La proporción de pacientes con ≥ 2 consultas a urgencias fue de 19,7% con el tratamiento basal y de 1,6% tras el cambio a budesonida/formoterol (p < 0,01). No se observaron diferencias significativas en la cantidad de hospitalizaciones. En este estudio del mundo real de pacientes con asma moderada a grave, el cambio del tratamiento a budesonida/formoterol se asoció con reducción significativa de las consultas a urgencias, a pesar de no detectarse cambios de significación estadística en los índices espirométricos habituales.

Asthma is characterized by its deleterious impact, including a high cost to the healthcare system. In patients with poorly controlled asthma despite treatment, a maintenance regimen of inhaled corticosteroids and formoterol is proposed. The aim of this retrospective, observational study was to evaluate the spirometric changes after switching the controller medication in patients with moderate to severe asthma attended in our institution ("Hospital Clínico de Magallanes"), as well as the variation in the number of severe exacerbations (consultation to an emergency department and/or hospitalization for asthma). Sixty-one adults with moderate to severe asthma (median age: 60 years-old [range: 21-87], women: 69.4%; atopic/allergic comorbidity: 79%; other comorbidities: 46.8%) in whom treatment with fluticasone/salmeterol 250/25 μg was switched to budesonide/formoterol 160/4.5 μg participated in our study. No significant changes in spirometric parameters were observed after the replacement treatment. With the initial treatment, 46.9% patients presented ≥ 1 visit to the emergency department (total: 50 visits). After the switch to budesonide/formoterol, 21% required at least one emergency department visit (total: 14 consultations; p < 0.01). The proportion of patients with ≥ 2 emergency department visits was 19.7% with baseline treatment and 1.6% after switching to budesonide/formoterol (p < 0.01). No significant differences were observed in the number of hospitalizations. In this real-world study of moderate to severe asthma patients, switching to budesonide/formoterol was associated with a significant reduction in emergency department visits, despite no statistically significant changes in the usual spirometric parameters.

Avances en tuberculosis en el 54° congreso chileno de enfermedades respiratorias. 1ra parte: nuevos esquemas acortados para tuberculosis drogoresistente ¿son adecuados para todos? / New shortened schemes for drug-resistant tuberculosis: are they suitable for everyone?

En esta presentación se realiza un recorrido a través de los diferentes esquemas terapéuticos de la tuberculosis drogo-resistente. Se muestra como los investigadores utilizan los nuevos fármacos disponibles y desarrollan diferentes esquemas cada vez más acortados y de administración por vía oral exclusiva, con la intención de lograr una mayor eficacia de curación de la tuberculosis resistente, con menos efectos colaterales y menor letalidad. La búsqueda de esquemas con una duración similar a las terapias de casos sensibles de tuberculosis (esquemas primarios de 6 meses) es el objetivo principal. Las pruebas moleculares como el Xpert ayudan enormemente a seleccionar los esquemas de terapia, según el perfil de susceptibilidad de los casos (resistencia a isoniazida, rifampicina, fluorquinolonas y combinaciones). Las terapias actuales de la tuberculosis drogo-resistente se basan en nuevos fármacos como fluorquinolonas, bedaquilina y linezolid, pero otros fármacos como pretomanid y delamanid también están siendo recomendados.

This presentation takes a tour through the different therapeutic schemes of drug-resistant tuberculosis. It shows how researchers use the new drugs available and develop different increasingly shortened schedules and exclusive oral administration, with the intention of achieving greater efficacy in curing resistant tuberculosis, with fewer side effects and lower lethality. The search for regimens with a duration similar to therapies of sensitive cases of tuberculosis (primary regimens of 6 months) is the main objective. Molecular tests, such as Xpert, greatly help in selecting therapy regimens, according to the susceptibility profile of the cases (resistance to isoniazid, rifampicin, fluorquinolones and combinations). Current drug-resistant tuberculosis therapies are based on new drugs such as fluorquinolones, bedaquiline and linezolid, but other drugs such as pretomanid and delamanid are also being recommended.

Higher-Dose Primaquine to Prevent Relapse of Plasmodium vivax Malaria.

BACKGROUND: In most of the Americas, the recommended treatment to prevent relapse of Plasmodium vivax malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy. METHODS: In this trial conducted in Brazil, we evaluated three primaquine regimens to prevent relapse of P. vivax malaria in children at least 5 years of age and in adults with microscopy-confirmed P. vivax monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days. RESULTS: We enrolled 63 patients in group 1, 96 in group 2, and 95 in group 3. The median age of the patients was 22.4 years (range, 5.4 to 79.8). By day 28, three P. vivax recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3. CONCLUSIONS: The administration of primaquine at a total dose of 7.0 mg per kilogram had higher efficacy in preventing relapse of P. vivax malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial.

AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

Short exposure to ethyl and methylmercury prompts similar toxic responses in Drosophila melanogaster.

Methylmercury (MeHg) and ethylmercury (EtHg) are important mercury organic forms in terms of human poisoning. Since the comparative effects of compounds are mainly in vitro, this study was designed to investigate the toxicities induced by MeHg and EtHg in an in vivo study using adult Drosophila melanogaster (D. melanogaster). Firstly, we performed a survival curve, where the flies were fed on a medium containing MeHg and EtHg at concentrations ranging from 2.5 to 200 µM, until the end of their lifespan. After that, the concentrations 25 and 200 µM of MeHg and EtHg were chosen to be tested in a short exposure for 5 days. The analysis of survival by Kaplan-Meier plot revealed that all concentrations of MeHg and EtHg reduced significantly the lifespan of the flies. Short exposure to both concentrations of MeHg and EtHg impaired the ability of flies in the climbing assay and induced lipid peroxidation. Only the flies exposed to the highest concentration had viability loss, thiol depletion, and increased reactive species (RS) and Hg levels in the whole body. Our findings indicate that MeHg and EtHg exhibit similar toxic effects in vivo, and that oxidative stress is a phenomenon behind the toxicity of both mercurials. The data obtained also reinforce the use of D. melanogaster as a useful organism for basic toxicological research.

Microbiology and Treatment Outcomes of Community-Acquired Hematogenous Osteoarticular Infections in Infants ≤12 Months of Age.

We investigated the microbiology, management, and orthopedic outcomes of osteoarticular infections in infants age ≤1 year at our institution. Among 87 patients, Staphylococcus aureus was the most common pathogen (44.8%), followed by group B Streptococcus. Twenty-nine patients (33%), with a median age of 9.2 months, were transitioned to oral antibiotic therapy after ≤14 days of parenteral therapy; orthopedic outcomes were similar to those with prolonged parenteral therapy.

Variability in Oral Desmopressin Dose Requirements in Children with Central Diabetes Insipidus.

There is inconsistency in the amount of oral desmopressin that children with central diabetes insipidus require. We investigated whether clinical characteristics influenced desmopressin dose requirements in 100 children with central diabetes insipidus. Extremely large doses were associated with acquired etiology (P = .04), greater body mass index z score, intact thirst, and additional pituitary hormone deficiencies (P < .001).

Magnesium sulfate vs aminophylline as a second line of treatment in children with severe acute asthma. Randomized clinical trial. / Sulfato de magnesio vs aminofilina como segunda línea de manejo en niños con asma aguda severa. Ensayo clínico aleatorizado.

INTRODUCTION: Second-line drugs for acute asthma, such as salbutamol, magnesium sulfate, and aminophylline, are generally intravenously administered. OBJECTIVE: To compare the efficacy and safety of using mag nesium sulfate or aminophylline in children who did not respond to initial treatment. PATIENTS AND METHOD: Randomized clinical trial. Children who did not improve the Modified Pulmonary Index Score (mPSI) receive at random magnesium sulfate (50 mg/kg/single dose) or aminophylline (5 mg/ kg/dose followed by continuous infusion at 1 mg/kg/hour for 3 hours). Primary endpoints were changes in mPSI and oxygen saturation; secondary endpoints: hospitalization rate, need for transfer to the intensive care unit, use of a third intervention, and adverse effects. RESULTS: 131 patients were studied (66 patients in the aminophylline group and 65 MgSO4). The mean age was 5 ± 2.3 years, the demographic and clinical parameters did not differ between the groups. In the group that received magnesium sulfate, the mPSI and oxygen saturation changed significantly in favor from 13.1 ± 1.3 to 4.9 ± 2.5 (p < 0.001) and from 3.3 ± 2.5; (p 0.021), respectively, and their risk of hospital admission (RR 0.68 95% CI [0.56, 0.82]) and of secondary failure (0.16 95% CI 95% [0 , 07; 0.38]) decreased. Only one adverse event (tachycardia) was recorded. CONCLUSION: The administration of a single dose of magnesium sulfate proved to be more effective and safe than the use of aminophylline as a second- line drug.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.