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Importance: Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit. Objective: To determine whether ivermectin is an efficacious treatment for mild COVID-19. Design, Setting, and Participants: Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state's health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020. Intervention: Patients were randomized to receive ivermectin, 300 µg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200). Main Outcomes and Measures: Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected. Results: Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group). Conclusion and Relevance: Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT04405843.
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Tratamento Farmacológico da COVID-19 , Ivermectina/uso terapêutico , Adulto , Idoso , Anti-Infecciosos/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Ivermectina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , SARS-CoV-2/isolamento & purificação , Fatores de Tempo , Falha de TratamentoRESUMO
Nanostructured lipid carriers (NLCs) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug, according to the Biopharmaceutical Classification System (BCS); it has a log P of 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study, we developed an NLC core consisting of a solid lipid (CrodamolTM CP), a lipophilic liquid with medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' types of drugs, including butamben. In this study, starting from the NLC core formulation previously developed we carried out an optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 23 factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI), and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped in stabilizing the system and decreasing particle size. NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI values lower than 0.3, and zeta potentials above |10|mV. Concerning NLCs' stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in an aqueous medium.
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Mercury (Hg) poses a health risk to wildlife populations and has been documented at relatively high concentrations in many marine mammals, including wild-caught pinnipeds along the central California, US coast. We measured total Hg concentrations ([THg]) in hair and blood of live-stranded harbor seals (HS; Phoca vitulina), California sea lions (CSL; Zalophus californianus), and northern elephant seals (NES; Mirounga angustirostris) in California to quantify species, temporal, and spatial variability in [THg] and assess the relationships between [THg] measured by different methods (blood vs. filter paper) and in different matrices (blood vs. hair). We compared [THg] with toxicologic thresholds of concern to aid in identification of at-risk individuals or groups and better understand how the use of different methods and matrices affects assumed toxicologic risk. There was a wide range of [THg] in blood (<0.01-1.13 µg/g) and hair (0.45-81.98 µg/g), and NES had higher [THg] compared with HS and CSL. All three species had individuals with [THg] that exceeded the lower threshold for one or both matrices, but only HS pups had [THg] exceeding upper thresholds. Spatial differences in [THg] were detected, with higher concentrations in HS pups from areas surrounding San Francisco Bay, but differences were dependent on sampling year and matrix. The relationship between [THg] in blood and filter paper (r2=0.98) was strong, and differences had little influence on comparisons with toxicologic thresholds. Blood and hair [THg] were generally in agreement (r2=0.72), but large mismatches for a few seals underscore the importance of combined sampling in adverse effects studies where accurate assessment of Hg exposure is crucial. The wide range of [THg] in stranded HS pups that exceeded published thresholds of concern makes them a promising candidate for adverse effects studies, particularly because different matrices represent Hg exposure across key developmental stages.
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Caniformia/sangue , Teste em Amostras de Sangue Seco/veterinária , Mercúrio/sangue , Poluentes Químicos da Água/sangue , Animais , Teste em Amostras de Sangue Seco/métodos , Monitoramento Ambiental/métodos , Cabelo/química , Mercúrio/químicaRESUMO
No disponible
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Humanos , Educação a Distância/tendências , Educação Médica/métodos , Infecções por Coronavirus , Pneumonia Viral , Pandemias , Modelos Educacionais , Educação Médica/organização & administração , Ensino/organização & administraçãoRESUMO
Resumen Objetivo: Identificar la prevalencia y las características del infarto agudo de miocardio en un programa de riesgo cardiovascular de una institución restadora de servicios en salud de primer nivel en Armenia, Quindío. Métodos: Se realizó un estudio descriptivo de corte transversal, que tomó como población las personas inscritas al programa de riesgo cardiovascular de una institución prestadora de servicios en salud de primer nivel del municipio de Armenia-Quindío, que consultaron por infarto agudo de miocardio entre el 1 de enero y 31 de diciembre de 2014; se describieron las variables en promedio, desviación estándar e intervalos de confianza, con un análisis comparativo por sexo para los factores de riesgo. Resultados y conclusiones: En la población del programa de riesgo cardiovascular se encontraron 293 casos con antecedente de infarto agudo de miocardio, con una prevalencia de 2,49%. La edad promedio en hombres fue de 66,62 años y en mujeres 69,58 años (p = 0,02). El colesterol HDL en hombres fue de 39,61 mg/dl y en mujeres de 46,58 mg/dl (p = 0,01). Los niveles de colesterol LDL se encontraron elevados según lo recomendado en prevención secundaria (110,04 mg/dl). El principal factor de riesgo encontrado fue la hipertensión arterial (84%), seguido por otros como el sedentarismo (63,48%), el sobrepeso y la obesidad (40,61 y 13,98% respectivamente), el hábito de fumar (12,97%) y el consumo de alcohol (5,46%), que fueron mayores en los hombres.
Absact Motivation: To identify the prevalence and characteristics of acute myocardial infarction in a cardiovascular risk programme conducted in a first-level institution providing health services in Armenia, Quindío. Meods: Cross-sectional descriptive study including participants in a cardiovascular risk programme of conducted in an institution providing health services in Armenia, Quindío, who consulted due to acute myocardial infarction between January 1st and December 31st 2014. Average variables, standard deviation and confidence intervals were described with a gender-based analysis for risk factors. Results and conclusions: 293 participants of the cardiovascular risk programme had a history of acute myocardial infarction, with a prevalence of 2.49%. Average age was 66.62 for men and 69.58 (p = 0.02) for women. HDL cholesterol was 39.61 mg/dl for men and 46.58 mg/dl (p = 0.01) for women. LDL cholesterol levels were high according to secondary prevention recommendations (110.04 mg/dl). The main risk factor found was arterial hypertension (84%), followed by others such as a sedentary lifestyle (63.48%), overweight and obesity (40.61 and 13.98% respectively), smoking (12.97%) and alcohol consumption (5.46%), which were more frequent amongst men.
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Humanos , Masculino , Feminino , Idoso , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Infarto do Miocárdio , Sobrepeso , Serviços de Saúde , Hipertensão , ObesidadeRESUMO
Blood was collected from stranded harbor seal (Phoca vitulina) pups at admission (n=64) and release (n=45) from rehabilitation in 2007 and 2008 and from wild-caught harbor seal pups, subadults, and adults (n=110) in 2004, 2007, and 2008. Blood values measured at the time of admission were not predictive of survival during rehabilitation. Mass was associated with survival until release, and all pups that died weighed less than 10 kg at the time of admission. Döhle bodies were observed in leukocytes from 15% to 22% of the pups in rehabilitation, but not in the wild pups. Thresholds (95% confidence intervals) among wild pups were less than those in the released pups for leukocytes, neutrophils, total cholesterol, alanine aminotransferase (ALT), glucose, phosphorus, sodium, potassium, total protein, albumin, and globulin; thresholds were greater in wild pups than in released pups for hemoglobin (HGB), hematocrit (HCT), and glucose. Thresholds among released pups were less than those in wild pups for HGB, HCT, mean cell volume, chloride, and creatine kinase; thresholds among released pups were greater than those in wild pups for neutrophils, platelets, total cholesterol, triglycerides, ALT, aspartate aminotransferase, sorbitol dehydrogenase, bilirubin, phosphorus, potassium, total protein, and albumin. Age, girth, and geographic location affected the blood variables from wild-caught pups; age class, geographic location, sex, and body condition affected the blood variables of wild-caught, subadult and adult harbor seals.