Detection of coca alkaloids in oral fluid from coca leaf (tea) consumers: using solid phase extraction to improve validation parameters and widen the detection window.

Hygrine and cuscohygrine, two coca leaf alkaloids, have been previously proposed as markers to differentiate legal and illegal cocaine consumption. This is a very common problem in some countries of South America, where the consumption of coca leaves has a long tradition. Analytical methods focusing on the assessment of coca leaf alkaloids, such as cuscohygrine, hygrine, tropacocaine and t-cinnamoylcocaine, in oral fluid are virtually non-existent in forensic toxicology laboratories worldwide due to their lack of application. However, the problem of differentiating legal and illegal cocaine use in criminal justice, DUID (drug-impaired driving) and WDT (workplace drug testing) programs is growing. Therefore, researchers are obliged to develop methods to measure coca leaf alkaloids (cuscohygrine, hygrine and t-cinnamoylcocaine) in biological matrices for further validation for routine analyses in forensic toxicology laboratories. This work aims to optimize a previously published separation method by protein precipitation in oral fluid by using solid-phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) operating in multiple reaction monitoring (MRM) mode. The use of SPE allowed the matrix effect and the background to be reduced in the chromatograms due to the obtained cleaner extracts. Consequently, improved detection and quantification limits were reached. Findings showed that the detection windows for coca leaf alkaloids were longer than three hours in real oral fluid samples from volunteers who drank a cup of coca tea. These detection windows are quite higher than those previously obtained when using the method based on separation by protein precipitation.

Disappearance of codeine, morphine and 6-MAM in hair after cessation of abuse.

Research on the determination of drugs of abuse in hair has established that drugs can be detected in hair even long after cessation of use. The purpose of this study was to analyze hair samples from chronic opioid users who were beginning a controlled drug cessation program. The study population (n = 15) is involved in a drug rehabilitation program in Santiago de Compostela, Spain. Over a 6-month period, subjects provided hair samples at 2-month intervals, with the first sample collected on the day they began the program. Codeine, morphine, and 6-MAM were analyzed by GC/MS (LOQ = 0.2 ng/mg). Hair tresses were divided into 1 cm segments and analyzed for all analytes 0-1 cm corresponding to the proximal portion to the scalp Following cessation of opioid use, traces of codeine, morphine, and 6-MAM still remained in the newly growing hair segments for a specified period. After 2 months, still 27 % of the users tested positive, and at 4 months, 20 % were positive but only for 6-MAM. However, after 6 months of abstinence, the results were negative for all analytes.

Sobredosis de acetaminofén y comportamientos relacionados con suicidio / Acetaminophen overdose and suicide-related behaviors / Overdose de paracetamol e comportamentos suicidas

Objetivo: este trabajo busca caracterizar el comportamiento relacionado con el suicidio en la población admitida al Hospital San Vicente Fundación, Rionegro, con sobredosis de acetaminofén entre enero 2019 y diciembre 2020 y detectar factores asociados con la dosis tóxica. Metodología: análisis descriptivo con información obtenida de historias clínicas. Resultados: 63 individuos presentaron ingestión aguda de dosis tóxica de acetaminofén como comportamiento relacionado con suicidio. Cuarenta y tres eran mujeres, 60% tenía antecedente de enfermedad psiquiátrica, 35% reportó al menos un intento suicida previo y 22% consumieron 25g o más. La lesión hepática aguda se asoció con una dosis tóxica. Conclusiones: evidenciamos una alta prevalencia de antecedente de enfermedad psi­quiátrica y comportamiento relacionado con suicidio y casi un tercio de los pacientes ingirió dosis mayores al umbral de riesgo para falla hepática. Además, la impulsividad e ingesta en casa sugiere que políticas públicas restrictivas pueden no impactar en la reducción de estos eventos en la población.

Objective: this work seeks to characterize the behavior related to suicide in the po­pulation admitted to the Hospital San Vicente Fundación, Rionegro, with an overdose of acetaminophen between January 2019 and December 2020, and to identify factors associated with the toxic dose. Methodology: descriptive analysis with information obtained from medical records. Results: 63 individuals presented acute ingestion of a toxic dose of acetaminophen as behavior related to suicide. Forty-three were women, 60% had a history of psychiatric illness, 35% reported at least one previous suicide attempt, and 22% consumed 25g or more. Acute liver injury was associated with a toxic dose. Conclusions: we evidenced a high prevalence of a history of psychiatric illness and beha­vior related to suicide; almost a third of the patients ingested doses greater than the risk threshold for liver failure. In addition, impulsiveness and eating at home suggests that res­trictive public policies may not have an impact on reducing these events in the population.

Objetivo: Este trabalho busca caracterizar o comportamento relacionado ao suicídio na população internada no Hospital San Vicente Fundación, Rionegro, com overdose de acetaminofeno entre janeiro de 2019 e dezembro de 2020 e detectar fatores associados à dose tóxica. Metodologia: análise descritiva com informações obtidas dos prontuários. Resultados: 63 indivíduos apresentaram ingestão aguda de dose tóxica de paracetamol como comportamento relacionado ao suicídio. Quarenta e três eram mulheres, 60% tinham histórico de doença psiquiátrica, 35% relataram pelo menos uma tentativa de suicídio anterior e 22% consumiram 25g ou mais. A lesão hepática aguda foi associada a uma dose tóxica. Conclusões: evidenciamos alta prevalência de história de doença psiquiátrica e com-portamento relacionado ao suicídio e quase um terço dos pacientes ingeriu doses superiores ao limiar de risco para insuficiência hepática. Além disso, a impulsividade e a alimentação em casa sugerem que políticas públicas restritivas podem não ter impacto na redução desses eventos na população.

Prescription patterns of somatostatin analogs in patients with acromegaly and neuroendocrine tumors.

PURPOSE: Acromegaly and neuroendocrine tumors are rare diseases that, under certain conditions, can be treated with somatostatin analogs. The aim was to determine the prescription patterns of somatostatin analogs in a group of patients with acromegaly and neuroendocrine tumors affiliated with the Colombian Health System. METHODS: A retrospective study. A cohort of patients from a drug dispensing database that collected all prescriptions of long-acting somatostatin analogs (octreotide, lanreotide, pasireotide). Sociodemographic variables, clinical variables (diagnosis and comorbidities) and pharmacological therapy variables (dose, changes, persistence of use, comedications) were considered. RESULTS: A total of 213 patients were identified, including 139 (65.3%) with acromegaly and 74 (34.7%) with neuroendocrine tumors. There was a predominance of women (58.7%) and a mean age of 59.7 ± 14.5 years. The most commonly used medications were lanreotide autogel (n = 107; 50.2%), octreotide LAR (n = 102; 47.9%) and pasireotide LAR (n = 4; 1.9%). During follow-up, 11.3% of patients experienced modifications of therapy, with a mean duration from the beginning of treatment to the change in medication of 25 ± 15.9 months. A total of 48.9% of the patients with acromegaly and 87.1% of individuals with neuroendocrine tumors received maximum approved doses of the drug. CONCLUSION: Patients with acromegaly and neuroendocrine tumors in Colombia are mainly women and are most frequently treated with lanreotide autogel for acromegaly and with octreotide LAR for neuroendocrine tumors. In addition, a high proportion are managed with maximum doses of long-acting somatostatin analogs.

Sexual Assault: Approach to Reality in the Area of Santiago de Compostela (Galicia, Spain) through a 12-Year Retrospective Study.

Sexual assault constitutes a severely traumatic experience that impacts the lives of far too many victims each year. The underlying behaviors of the offenders are often associated with psychological, physical and social distress, and the use of psychotropic substances was found in a good number of cases. A descriptive and retrospective review of sexual assault cases has been undertaken to identify trends in the toxicology findings in Drug-Facilitated Sexual Assault in Santiago de Compostela over the past 12 years. During this period, a total of 69 cases were referred to the Forensic Toxicology Service as sexual assault cases. The sex and age distribution of the cases showed that females between the ages of 14 and 65 years constituted the group most frequently submitted to sexual assault, with a peak of 55.1% in the 18- to 30-year age group. Alcohol consumption was positive in 77.1% of positive cases determined, followed by drugs (34.4%) and illicit drugs (26.2%). Our results showed a high percentage of alcohol consumption in sexual assault cases.

Perfil epidemiológico de pacientes intoxicados con acetaminofén con intenciones suicidas / Epidemiological profile of patients intoxicated with acetaminophen for suicidal purposes / Perfil epidemiológico de pacientes intoxicados com acetaminofen (Paracetamol) com intenções suicidas

Objetivo: este estudio busca describir los individuos evaluados por sobredosis de acetaminofén entre 2019 y 2020 en un centro de referencia de trasplante hepático en Colombia. Metodología: estudio derivado del análisis secundario de historias clínicas entre el 1.º de enero de 2019 y el 31 de diciembre de 2020. Los criterios de inclusión abarcan individuos con ingestión aguda y voluntaria de dosis tóxicas de acetaminofén (>4 g/día). Resultados: sesenta y tres casos, 68% mujeres, 67% menores de 18 años y 54% estudiantes. Reportó historia personal de enfermedad psiquiátrica el 60% y el 35% al menos un intento de suicidio previo. La mediana de dosis de acetaminofén fue 15g, 46% refirieron co-ingesta de otras sustancias y 13% estaba bajo efecto de sustancias psicoactivas. El 57% tenía la intención clara de suicidarse, así como 81% vomitó antes de acudir al servicio de urgencias, 22% recibió medidas de descontaminación y 10% no recibió N - acetilcisteína. Quince individuos desarrollaron lesión hepática aguda, nueve con criterios de severidad. Conclusiones: la población era predominantemente joven, la historia de enfermedad psiquiátrica fue muy prevalente y la mayoría refirieron un evento vital que explicara el comportamiento impulsivo de consumo. Ninguno desarrolló criterios para trasplante hepático, lo cual podría explicarse por la edad de los individuos, los episodios de vómito temprano, y la ausencia de enfermedad hepática crónica o de consumo de sustancias hepatotóxicas.

Objective: this study aims to describe patients with overdose intake of acetaminophen between 2019 and 2020 at a reference center for liver transplantation in Colombia. Methodology: study derived from a secondary analysis of the clinical records between January 1st, 2019, to December 31st, 2020. Inclusion criteria were individuals with voluntary acute ingestion of toxic doses of acetaminophen (>4 g/day). Results: sixty-three cases, 68% women, 67% <18-year-old, and 54% students. 60% had personal history of psychiatric illness and 35% reported at least one previous suicide attempt. The median dose of acetaminophen was 15g, 46% referred to co-ingestion with other substances and 13% were under the effect of any psychoactive substance. 57% had a clear intention of suicide. 81% vomited before the arrival to the emergency room, 22% received decontamination intervention with gastric lavage or activated charcoal, and 10% did not receive any dose of N-Acetylcysteine. Fifteen individuals developed an acute liver injury, nine with severity criteria. Conclusions: the population was predominantly young, the personal history of psychiatric disease was highly prevalent, and most of the cases referred a vital event that explains the impulsive behavior in acetaminophen consumption. None developed criteria for liver transplantation, and this could be explained by the young age of the individuals, the episodes of early vomiting, and the absence of chronic liver disease or hepatotoxic substance consumption.

Objetivo:este estudo busca descrever os indivíduos avaliados por sobredose de acetaminofen entre 2019 e 2020 num centro de referência de transplante hepático na Colômbia. Metodologia: estudo derivado da análise secundário de histórias clínicas entre o dia 1.º de janeiro de 2019 e 31 de dezembro de 2020. Os critérios de inclusão abrangem indivíduos com ingestão aguda e voluntária de dose tóxicas de acetaminofen (>4 g/dia).Resultados:sessenta e três casos, 68% mulheres, 67% menores de 18 anos e 54% estudantes. Reportou história pessoal de doença psiquiátrica, 60% e 35% pelo menos uma tentativa de suicídio prévio. A média de dose de acetaminofen foi de 15g, 46% referiram com ingestão de outras sustâncias e 13% estava sob efeito de sustâncias psicoativas. 57% tinham a intenção clara de suicidar-se, assim como 81% vomitou antes de acudir ao serviço de urgências, 22% receberam medidas de descontaminação e 10% não recebeu N - acetilcisteína. Quinze indivíduos desenvolveram lesão hepática aguda, nove com critérios de severidade. Conclusões: a população era predominantemente jovem, a história de doençapsiquiátrica foi muito prevalente e a maioria referiram um evento vital que explicasse o comportamento impulsivo de consumo. Nenhum desenvolveu critérios para transplantehepático, o qual se poderia explicar pela idade dos indivíduos, os episódios de vómito precoce, e a ausência de doença hepática crónica ou de consumo de sustâncias hepatotóxicas.

Topical finasteride dose evaluation for treatment of androgenetic alopecia using computer simulations.

OBJECTIVE: Our objective was to evaluate the absorption of finasteride administered by oral and topical routes for treatment of androgenetic alopecia, by means of computer simulations using the GastroPlus ® software. MATERIAL AND METHODS: In vivo plasma concentration profile of oral administration of finasteride 1 mg tablets from the literature was used in the software to build a compartmental pharmacokinetic model that was extrapolated to simulate topical administration of finasteride 0.25% solution in the scalp. Results were compared to literature and other drug concentrations (0.1% and 1%) were also predicted. RESULTS: Compared to literature data, predictive plasma curve from oral administration of finasteride 1 mg showed good correlation, R2=0.992, and Cmax=4.6769 ng/mL. Simulations of topical administration in the scalp for finasteride 0.25% solution showed good correlation, R2=0.908, and Cmax=0.04325 ng/mL when compared to literature data. Topical administration was also simulated at concentrations 0.1% and 1%, both with low plasma concentrations. CONCLUSION: The results obtained in this study suggest that topical finasteride is a potential treatment for androgenetic alopecia in the concentrations analyzed using computer simulations in GastroPlus ®.

Patrones de resistencia en agentes bacterianos involucrados en otitis caninas en Medellín, Colombia, durante 2019: análisis retrospectivo / Patterns of resistance in bacterial agents involved in canine otitis at Medellín, Colombia, during 2019: retrospective analysis

RESUMEN Dentro de los agentes patógenos en los procesos otíticos bacterianos, se destacan microorganismos como Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabi-lis, Escherichia coli, Corynebacterium spp., Enterococcus spp. y Streptococcus spp., para los cuales se ha descrito resistencia frente a los antibióticos empleados para combatirlos. En Colombia son pocos los reportes acerca de la resistencia antibiótica de microorganismos causantes de otitis. Por ello, el objetivo de esta investigación fue determinar los agentes bacterianos más frecuentemente aislados en infecciones otíticas de caninos remitidas a un laboratorio veterinario de Medellín durante el 2019 y su resistencia a antibióticos. Para llevarlo a cabo, se realizó un estudio descriptivo transversal retrospectivo. Se analizaron los resultados de los antibiogramas realizados a partir de cultivos bacterianos en muestras óticas remitidas a un laboratorio de referencia de la ciudad de Medellín. Además, se efectuó un análisis de frecuencias para la muestra total. Se encontró que los principales microorganismos bacterianos aislados fueron Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabili y Staphylococcus aureus. La gentamicina fue el medicamento que mayor porcentaje de resistencia presentó y la cefalexina el que menos resistencia presentó. Se pudo concluir que el Staphylococcus pseudintermedius está presente en más del 60% de los casos de otitis bacteriana. Adicionalmente, se observó una variación de la resistencia presentada por los microorganismos en el tiempo. Estos presentaron mayor resistencia ante los antibióticos aminoglucósidos.

ABSTRACT Among the pathogens in bacterial otic processes, microorganisms such as Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabilis, Escherichia coli, Corynebac-terium spp., Enterococcus spp., and Streptococcus spp. stand out, for which resistance to antibiotics has been described employed to combat them. In Colombia there are few reports about the antibiotic resistance of microorganisms that cause otitis. For that reason, the purpose of this study was to determine the bacterial agents most frequently isolated from canine ear infections and their resistance to antibiotics from samples of ear secretions sent to a veterinary laboratory in Medellín during 2019. In order to do that, an cross-sectional, retrospective descriptive study was done. The results of the antibiograms performed from bacterial cultures obtained from ear samples sent to a reference laboratory in the city of Medellín were analyzed. A frequency analysis was carried out for the total sample. It was found that the main isolated bacterial microorganisms were Staphylococcus pseudintermedius, Pseudomona auriginosa, Proteus mirabili and Staphylococcus aureus. Gentamicin was the drug with the highest percentage of resistance and cephalexin the one with the least resistance. It was possible to conclude that Staphylococcus pseudintermedius is linked in more than 60% of cases of bacterial otitis and the resistance presented by microorganisms varies over time. The group of aminoglycosides antibiotics was the one which microorganisms are manifesting more percentage of resistance.

Afecciones cutáneas en trabajadores con empleos de subsistencia y su relación con factores socioambientales y laborales. Medellín, Colombia / Skin conditions in workers with subsistence jobs and related socio-environmental and labor factors. Medellin Colombia

Introducción: La información acerca de lesiones en piel y sus factores asociados, en trabajadores informales en América Latina y el Caribe aun es escasa. Objetivo: Determinar la relación existente entre las condiciones sociodemográficas, ambientales, laborales y la prevalencia de afecciones en la piel auto-reportada por trabajadores informales “venteros” del centro de Medellín. Material y Métodos: Estudio transversal con intención analítica y fuente primaria de información. Se incluyeron 686 trabajadores. Se aplicó encuesta asistida, previa realización de prueba piloto y estandarización de los encuestadores. Variable dependiente; prevalencia de afecciones en piel. Variables independientes; condiciones laborales, sociodemográficas y ambientales. Se realizó control de errores con análisis estadísticos y sesgos de selección e información. Se realizaron análisis univariado, bivariado y multivariado. Resultados: Trabajadores fundamentalmente hombres (57.6%), edades entre 45-59 años, 60,0% procedente de zona rural. Trabajaban > 8 horas/día (80,6%), toda la semana, con > 20 años (50,7%) en su labor. El 72,2% no utilizaba mecanismos de protección personal. 61,5% consideraba que la contaminación ambiental afectaba su labor y su salud. 19,83% presentó afectaciones cutáneas, como; alergias (12,0%), prurito y sarpullido. Menor prevalencia de alergias en hombres (24,0%) y ≥ 60 años. Mayores prevalencias en quienes laboraban >8 horas/día (94,0%), toda la semana (43,0%), con exposición a sustancias químicas (RP=1,88.IC=1,11;3,20), vendedores de mercancía y cacharro (RP =2,06.IC: 1,08;3,91). Conclusión: Explican mayor prevalencia de alergias proceder de la zona urbana, vender mercancía y cacharro, trabajar >8 horas/día, toda la semana, exponerse a sustancias químicas, considerar que la calidad del aire afecta su labor, y presentar comorbilidades (AU)

Introduction: The information on skin lesions and their associated factors in informal workers in Latin America is scarce. Objective: To determine the existing relationship between sociodemographic, environmental and labor conditions and the prevalence of skin conditions, self-reported by informal workers “venteros” from the Medellin downtown. Material and Methods: Cross-sectional study with analytical intention and primary source of information. 686 workers were included. An assisted survey was applied, after conducting a pilot test and standardization of the interviewers. The presence of skin conditions was considered as the dependent variable and the working, sociodemographic and environmental conditions as independent variables. Error control was performed with statistical analysis, selection and information biases were controlled. Univariate and bivariate analysis was performed. Results: Mainly male workers (57.6%), ages 45-59 years, 60.0% from rural areas. They worked> 8 hours / day (80.6%), all week, with> 20 years (50.7%) in their work. 72.2% did not use personal protection mechanisms. 61.5% considered that environmental pollution affected their work and their health. 19.83% presented skin affectations, such as allergies (12.0%), pruritus and rash. Lower prevalence of allergies in men (24.0%) and ≥60 years. Higher prevalences in those who worked> 8 hours / day (94.0%), all week (43.0%), with exposure to chemical substances (PR = 1.88, IC = 1.11, 3.20), sellers of merchandise and equipment (PR = 2.06.IC: 1.08; 3.91). Conclusion: They explain a higher prevalence of allergies coming from the urban area, selling merchandise and junk, working> 8 hours / day, all week, being exposed to chemical substances, considering that air quality affects their work, and presenting comorbidities (AU)

COVID-19 symptoms: a case-control study, Portugal, March-April 2020.

COVID-19, although a respiratory illness, has been clinically associated with non-respiratory symptoms. We conducted a negative case-control study to identify the symptoms associated with SARS-CoV-2-positive results in Portugal. Twelve symptoms and signs included in the clinical notification of COVID-19 were selected as predictors, and the dependent variable was the RT-PCR test result. The χ2 tests were used to compare notified cases on sex, age group, health region and presence of comorbidities. The best-fit prediction model was selected using a backward stepwise method with an unconditional logistic regression. General and gastrointestinal symptoms were strongly associated with a positive test (P < 0.001). In this sense, the inclusion of general symptoms such as myalgia, headache and fatigue, as well as diarrhoea, together with actual clinical criteria for suspected cases, already updated and included in COVID-19 case definition, can lead to increased identification of cases and represent an effective strength for transmission control.

Determination of Seven Antidepressants in Pericardial Fluid by Means of Dispersive Liquid-Liquid Microextraction (DLLME) and Gas Chromatography-Mass Spectrometry (GC/MS).

Although blood is often used to detect and quantify the presence of drugs, there are some instances where samples obtained from other biological matrices, like pericardial fluid (PF), are necessary since adequate blood samples may not be available. PF is an epicardial transudate, which contains plasma components that include toxicological substances making this sample useful when blood samples are not available. This fluid is a well preserved postmortem sample and can easily be collected in larger amounts without significant contamination, compared with other body fluids. Although studies involving PF began around the 1980's, the adequacy of such fluid as a biological matrix has been poorly investigated. Antidepressants are frequently detected in postmortem samples from forensic cases. Nowadays, they constitute some of the most commonly prescribed drugs worldwide. A total of seven antidepressants (venlafaxine, mirtazapine, olanzapine, paroxetine, sertraline, fluoxetine and citalopram) were evaluated in this study. A new extraction method involving dispersive liquid-liquid microextraction (DLLME) is presented in which chloroform and acetonitrile are determined to be the best extraction and dispersing solvents. The experimental design was achieved using StatGraphics 18. The Response Surface Methodology enabled us to know the optimal volume for the two solvents used in the DLLME. The detection technique used was gas chromatography-mass spectrometry (GC-MS) with electron impact ionization as ionization source. A temperature gradient has been used and the total chromatographic separation time was 19.43 min. Validation results met the international validation guidances (FDA). Under the optimal condition, the method offered good validation parameters showing a new efficient, simple, rapid, and sensitive method. The analytical method was applied to thirty-one pericardial fluid samples. Twenty-one samples were positive with concentrations between 0.19 and 8.48 µg/mL. Venlafaxine and olanzapine were the antidepressants most frequently found.

Perspectiva de los profesionales de la salud sobre cuidados al final de la vida en unidades de cuidados intensivos / Perspective of health personnel on end-of-life care in Intensive Care Units

OBJETIVO: Comprender el sentido otorgado por los profesionales de la salud de la Unidad de Cuidado Intensivo (UCI), respecto a los cuidados del paciente al final de la vida, y de sus familiares. MÉTODOS: Estudio cualitativo con un diseño Investigación-Acción (IA), en dos UCIs de la ciudad de Bogotá. Se formó un grupo en cada unidad, cada uno incluyó mínimo seis trabajadores de la salud. Las técnicas de recogida de datos fueron: 4 Asambleas participativas y 6 narrativas clínicas. El análisis de datos incluyó la preparación de los datos, descubrimiento de temas, codificación e interpretación de datos, relativización y rigor de los datos. RESULTADOS: Participaron 20 trabajadores de UCI, del análisis de los datos emergieron cuatro categorías: Equipo multidisciplinario de UCI frente al proceso de fin de vida, Manejo del paciente crítico y de su familia, al final de la vida en UCI, Proceso de Comunicación entre el paciente, familia y equipo multidisciplinario al final de la vida, Aspectos éticos al final de la vida en la UCI. CONCLUSIONES: Los profesionales conciben como un objetivo terapéutico, preservar la calidad de vida durante la estancia del paciente en UCI. Para los profesionales de la salud, es fundamental desarrollar guías basadas en la evidencia que faciliten el manejo multidisciplinar al final de la vida, la personalización de la atención, la comunicación efectiva, la satisfacción de las necesidades físicas, emocionales y espirituales de la persona y su familiar y favorecer el derecho de autonomía del paciente en la toma de decisiones

OBJECTIVE: To understand for what care of the patient at the end of life and their relatives means to ICU health professionals. METHODS: Qualitative study with a Research-Action (AI) design, in two intensive care units of the city of Bogotá. Groups were formed in each unit and each group included at least six health professionals, the data collection techniques were: 4 participative assemblies and 6 clinical narratives, the data analysis was done through the preparation of the data, discovery of topics, coding and interpretation of data, relativisation and rigour of the data. RESULTS: 20 ICU workers participated, the analysis of the data revealed four thematic categories: Multidisciplinary team of the ICU facing the end-of-life process, Management of critical patients and their families at the end of life in the ICU, Communication process between the patient, family and multidisciplinary team at the end of life, Ethical aspects at the end of life in the ICU. CONCLUSIONS: The professionals consider preserving quality of life during the patient's stay in the ICU a therapeutic objective. The development of evidence-based guidelines that facilitate multidisciplinary management at the end of life, customisation of care, effective communication, fulfilling the physical, emotional and spiritual needs of the person and their family and favouring the patient's right of autonomy in decision making

Perspective of health personnel on end-of-life care in Intensive Care Units. / Perspectiva de los profesionales de la salud sobre cuidados al final de la vida en unidades de cuidados intensivos.

OBJECTIVE: To understand for what care of the patient at the end of life and their relatives means to ICU health professionals. METHODS: Qualitative study with a Research-Action (AI) design, in two intensive care units of the city of Bogotá. Groups were formed in each unit and each group included at least six health professionals, the data collection techniques were: 4 participative assemblies and 6 clinical narratives, the data analysis was done through the preparation of the data, discovery of topics, coding and interpretation of data, relativisation and rigour of the data. RESULTS: 20 ICU workers participated, the analysis of the data revealed four thematic categories: Multidisciplinary team of the ICU facing the end-of-life process, Management of critical patients and their families at the end of life in the ICU, Communication process between the patient, family and multidisciplinary team at the end of life, Ethical aspects at the end of life in the ICU CONCLUSIONS: The professionals consider preserving quality of life during the patient's stay in the ICU a therapeutic objective. The development of evidence-based guidelines that facilitate multidisciplinary management at the end of life, customisation of care, effective communication, fulfilling the physical, emotional and spiritual needs of the person and their family and favouring the patient's right of autonomy in decision making.

Prevalence of peripheral neuropathy associated with chemotherapy in four oncology centers of Colombia. / Prevalencia de neuropatia periferica asociada a quimioterapia en cuatro centros oncologicos de Colombia.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy is a common adverse reaction in a variety of medications frequently used for a great number of cancer treatments. This condition consists of mainly sensory-type symptoms, motor components and autonomic changes. Reported prevalence ranges from 30-68%, after the completion of chemotherapy in non-Latin American people with different populations and socioeconomic levels. AIM: To determine the prevalence of chemotherapy-induced peripheral neuropathy in a Colombian population. PATIENTS AND METHODS: A real-world evidence cross-sectional retrospective study was performed in all patients from oncological clinical centers in Colombia, which received pharmacological therapy for any cancer between January 2015 and December 2016, with taxanes (paclitaxel, docetaxel), alkylators (oxaliplatin), proteasome inhibitors (bortezomib), and epothilone B analogs (ixabepilone). RESULTS: A total of 1,551 patients in four cities were included, and 11,280 doses were applied; predominantly females (n = 1,094; 70.5%), with a mean age of 57 ± 13 years old. Paclitaxel was the most commonly prescribed drug (n = 788; 50.8%). Chemotherapy-induced peripheral neuropathy was developed in 48.9% of paclitaxel, 58.5% of oxaliplatin, 50.5% of docetaxel, 43.7% of bortezomib and 95.2% of ixabepilone patients. Thirty-three patients were treated with two of these medications simultaneously. CONCLUSIONS: Chemotherapy-induced peripheral neuropathy is a frequent adverse reaction to daily cancer therapy in Colombian patients managed with taxanes, alkylators, proteasome inhibitors, and epothilone B analogs. Hence, it is necessary to establish more successful diagnostic methods and incorporate validated scales in the routine evaluation of all patients receiving these medications in our environment.

TITLE: Prevalencia de neuropatia periferica asociada a quimioterapia en cuatro centros oncologicos de Colombia.Introduccion. La neuropatia periferica inducida por quimioterapia es una reaccion comun a una variedad de medicamentos usados en el tratamiento del cancer, que consiste principalmente en sintomas sensitivos, con componentes motores y cambios autonomicos. La prevalencia es del 30-68% despues de terminar la quimioterapia en paises no latinoamericanos. Objetivo. Determinar la prevalencia de la neuropatia periferica inducida por quimioterapia en la poblacion colombiana. Pacientes y metodos. Estudio retrospectivo con evidencia del mundo real en la totalidad de pacientes atendidos en cuatro centros oncologicos de Colombia, quienes recibieron terapia farmacologica para algun tipo de cancer entre enero de 2015 y diciembre de 2016 con taxanos (paclitaxel, docetaxel), agentes alquilantes (oxaliplatino), inhibidores de proteasoma (bortezomib) y analogos de epotilona B (ixabepilona). Resultados. Se siguio a un total de 1.551 pacientes en cuatro ciudades a quienes se les aplicaron 11.280 dosis, con predominio femenino (n = 1.094; 70,5%) y una edad media de 57 ± 13 años. El paclitaxel fue el farmaco mas prescrito (n = 788; 50,8%). La neuropatia inducida por quimioterapia se presento en el 48,9% de los pacientes con paclitaxel, el 58,5% de los pacientes con oxaliplatino, el 50,5% de los pacientes con docetaxel, el 43,7% de los pacientes con bortezomib y el 95,2% de los pacientes con ixabepilona. Se trato a 33 pacientes con dos de estos medicamentos simultaneamente. Conclusiones. La neuropatia periferica inducida por quimioterapia es una reaccion adversa frecuente en pacientes con cancer en Colombia tratados con taxanos, alquilantes, inhibidores de proteasoma e ixabepilona. Es necesario establecer metodos diagnosticos efectivos e incorporar escalas validadas en la evaluacion rutinaria de los pacientes que reciben estas medicaciones.

Enhanced supply of methionine or arginine alters mechanistic target of rapamycin signaling proteins, messenger RNA, and microRNA abundance in heat-stressed bovine mammary epithelial cells in vitro.

Heat stress (HS) causes reductions in milk production, but it is unclear whether this effect is due to reduced number or functional capacity (or both) of mammary cells. Methionine supplementation improves milk protein, whereas Arg is taken up in excess by mammary cells to produce energy and nonessential AA that can be incorporated into milk protein. To evaluate molecular mechanisms by which mammary functional capacity is affected by HS and Met or Arg, mammary alveolar (MAC-T) cells were incubated at thermal-neutral (37°C) or HS (42°C) temperatures. Treatments were optimal AA profiles (control; Lys:Met = 2.9:1.0; Lys:Arg = 2.1:1.0), control plus Met (Lys:Met = 2.5:1.0), or control plus Arg (Lys:Arg = 1.0:1.0). After incubation for 6 h, cells were harvested and RNA and protein were extracted for quantitative real-time PCR and Western blotting. Protein abundance of mechanistic target of rapamycin (MTOR), eukaryotic initiation factor 2a, serine-threonine protein kinase (AKT), 4E binding protein 1 (EIF4EBP1), and phosphorylated EIF4EBP1 was lower during HS. The lower phosphorylated EIF4EBP1 with HS would diminish translation initiation and reduce protein synthesis. Both Met and Arg had no effect on MTOR proteins, but the phosphorylated EIF4EBP1 decreased by AA, especially Arg. Additionally, Met but not Arg decreased the abundance of phosphorylated eukaryotic elongation factor 2, which could be positive for protein synthesis. Although HS upregulated the heat shock protein HSPA1A, the apoptotic gene BAX, and the translation inhibitor EIF4EBP1, the mRNA abundance of PPARG, FASN, ACACA (lipogenesis), and BCL2L1 (antiapoptotic) decreased. Greater supply of Met or Arg reversed most of the effects of HS occurring at the mRNA level and upregulated the abundance of HSPA1A. In addition, compared with the control, supply of Met or Arg upregulated genes related to transcription and translation (MAPK1, MTOR, SREBF1, RPS6KB1, JAK2), insulin signaling (AKT2, IRS1), AA transport (SLC1A5, SLC7A1), and cell proliferation (MKI67). Upregulation of microRNA related to cell growth arrest and apoptosis (miR-34a, miR-92a, miR-99, and miR-184) and oxidative stress (miR-141 and miR-200a) coupled with downregulation of fat synthesis-related microRNA (miR-27ab and miR-221) were detected with HS. Results suggest that HS has a direct negative effect on synthesis of protein and fat, mediated in part by coordinated changes in mRNA, microRNA, and protein abundance of key networks. The positive responses with Met and Arg raise the possibility that supplementation with these AA during HS might have a positive effect on mammary metabolism.

Determination of benzodiazepines in pericardial fluid by gas chromatography-mass spectrometry.

In Forensic Toxicology it is sometimes impossible to obtain a valid blood sample to perform toxicological analysis due to several factors like advanced state of decomposition, severe burns, bleed to death…. Pericardial Fluid has already been studied during the last years and has been proposed as a valid specimen for toxicological tests. Over the years, the consumption of benzodiazepines spread among the drug dependent population and became noticeable in drug facilitated assault cases and road accidents. Improvement of the analytical methodology required for detecting the presence of these drugs in biological samples is of great importance for forensic toxicology, in order to correctly diagnose an exposure or a poisoning. In this study, 9 benzodiazepines (diazepam, nordiazepam, midazolam, bromazepam, oxazepam, temazepam, lorazepam, clonazepam and alprazolam) have been determined in pericardial fluid. For this purpose a solid phase extraction (SPE) was carried out using Bond Elut Certify cartridges. After the derivatization of six of the nine benzodiazepines, gas chromatography coupled to a selective mass detector was used as the technique for the separation of the analytes. The method developed was fully validated for the 9 analytes and was applied to real samples of pericardial fluid received at the Forensic Toxicology Service of the University of Santiago de Compostela. Finally, they were compared with blood results looking for the existence of a possible correlation between both biological samples.

Tumor Biology as Predictor of Mortality in Liver Transplantation for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most frequent primary malignant liver tumor, with the Milan criteria considered to be the gold standard for patient selection for liver transplantation (LT). MATERIALS AND METHODS: We performed a descriptive observational study, reviewing 20 years of experience of LT in patients with HCC in the Fundacion Valle del Lilí in Cali, Colombia. Subgroup analysis was undertaken for periods 1999 to 2007 and 2008 to 2015. RESULTS: Fifty-seven cases with a pretransplant HCC diagnosis were reviewed. In the first period patients within the Milan criteria had a recurrence-free survival at 5 years of 66.6%, and in those who exceeded the Milan criteria, recurrence-free survival was 75%. In the second period, patients within the Milan criteria, recurrence-free survival at 5 years was 93.5%, and in those who exceeded the Milan criteria, recurrence-free survival was 75.7%. No statistically significant difference was found in either period. For patients with mild and moderate tumor differentiation, the relapse survival rate at 5 years was 69.4% (95% confidence interval [CI] 35.8-87.8) and 74.7% (95% CI 44.5-90), respectively. All patients with poor tumor differentiation relapsed and died within 3 years. CONCLUSION: Global and recurrence-free survival among patients who met and patients who exceeded the Milan criteria was not significantly different, suggesting an expansion of the Milan criteria to include potential recipients who were previously excluded. Obtaining histologic differentiation and identifying vascular invasion will provide a more worthwhile contribution to LT decision making.

Trends in the use and cost of human and analogue insulins in a Colombian population, 2011-2015.

OBJECTIVES: Diabetes mellitus is a common disease among the general population and imposes considerable costs on health care systems. Insulin is used to treat type 1 diabetes mellitus and as an adjuvant to oral agents in advanced stages of type 2 diabetes mellitus. The objective was to describe the trends in use and cost of human and analogue insulins for Colombian patients. STUDY DESIGN: Descriptive retrospective analysis of prescriptions of human and analogue insulins on a monthly basis for the period from July 1, 2011 to February 2, 2015. METHODS: Information was collected for the database population of two insurance companies. Frequencies and proportions were calculated; estimated economic impact was expressed as net cost and cost per thousand inhabitants per day. RESULTS: During the observation period, there was continuous growth in use of insulin, mainly in analogue forms (34.0% growth). At the start of the study, 10.4% of subjects were using an analogue insulin; this figure was 62.6% at the end of the study. In 2012, the average cost per 1000 inhabitants/day was US$1.7 for analogue and US$0.8 for human insulins. At the end of the observation period these costs had risen to US$9.2 for analogue (441.1% increase) and fallen to US$0.5 for human insulin (58.3% decrease). CONCLUSIONS: There has been an increase in the unit cost and frequency of use of insulin analogues for anti-diabetic therapy in Colombian patients. Moreover, there is controversy over whether insulin analogues are a more cost-effective treatment than human insulins for the general diabetic population.

International trends in clozapine use: a study in 17 countries.

OBJECTIVE: There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis. METHOD: A repeated cross-sectional design was applied to data extracts (2005-2014) from 17 countries worldwide. RESULTS: In 2014, overall clozapine use prevalence was greatest in Finland (189.2/100 000 persons) and in New Zealand (116.3/100 000), and lowest in the Japanese cohort (0.6/100 000), and in the privately insured US cohort (14.0/100 000). From 2005 to 2014, clozapine use increased in almost all studied countries (relative increase: 7.8-197.2%). In most countries, clozapine use was highest in 40-59-year-olds (range: 0.6/100 000 (Japan) to 344.8/100 000 (Finland)). In youths (10-19 years), clozapine use was highest in Finland (24.7/100 000) and in the publicly insured US cohort (15.5/100 000). CONCLUSION: While clozapine use has increased in most studied countries over recent years, clozapine is still underutilised in many countries, with clozapine utilisation patterns differing significantly between countries. Future research should address the implementation of interventions designed to facilitate increased clozapine utilisation.