Aceptación, rechazo y vacilación a recibir la vacuna contra COVID-19: estudio multicéntrico / Acceptance, rejection and hesitancy to receive the vaccine against COVID-19: a multicenter study

Objetivos: Determinar la predisposición a recibir esta vacuna contra SARS-CoV-2. Materiales y métodos: Se aplicó un diseño observacional de corte transversal en la población adulta del Paraguay entre mayo y octubre 2022. se aplicó el cuestionario de Kotta et al previamente validado, el cual fue difundido por redes sociales. Resultados: Se incluyeron 303 encuestados, con edad media 34 ± 12 años y predominio del sexo femenino (64,0%). En la muestra, 51,8% padeció COVID-19 y 97,3% ya recibió al menos una dosis de la vacuna. Se detectó que 58,4% aceptada la vacuna, 17,8% vacilaba en recibirla y 23,7% la rechazaba. La aceptación fue más frecuente en los varones (p 0,05). Conclusión: En el momento epidemiológico de disponibilidad universal de la vacuna y habiendo aún sujetos afectados por COVID-19, el rechazo a la misma fue 23,7%.

Objectives: To determine the predisposition to receive this vaccine against SARS-CoV-2. Materials and methods: An observational cross-sectional design was applied in the adult population of Paraguay between May and October 2022. The previously validated questionnaire of Kotta et al was applied, which was disseminated through social networks. Results: 303 respondents were included, with a mean age of 34 ± 12 years and predominance of the female sex (64.0%). In the sample, 51.8% suffered from COVID-19 and 97.3% have already received at least one dose of the vaccine. It was detected that 58.4% accepted the vaccine, 17.8% hesitated to receive it and 23.7% rejected it. Acceptance was more frequent in males (p 0.05). Conclusion: At the epidemiological moment of universal availability of the vaccine and with subjects still affected by COVID-19, rejection of it was 23.7%.

Development of a web tool to calculate the cumulative dose of glucocorticoids / Desarrollo de una herramienta web para calcular la dosis acumulada de corticoides

Introduction: Glucocorticoids are associated with serious side effects related to dosing and time of use. Unfortunately, there is no standard method for determining glucocorticoid exposure, especially in patients undergoing long-term treatment. Objective: The aim of this work was to create a free and easy-to-use web application to calculate, in a systematic way, the total cumulative dose of corticosteroids. Methods: The total cumulative dose is calculated as the sum of all periods of treatment with different doses of corticosteroids, and is expressed as the equivalent dose of prednisone in mg. Glucocorticoid doses during periods in which the available information is missing or incomplete are estimated by systematic assumptions. Results: A simulation exercise using standard patterns of steroid use in polymyalgia rheumatica, and giant cell arteritis showed that even when the period of no information reached 50% of the time, the accuracy of the calculator had a mean absolute percentage error (MAPE)<7%. Conclusion: This tool simplifies and standardizes the glucocorticoids cumulative dose calculation, thereby minimizing bias in the assessment of glucocorticoid cumulative dose.(AU)

Introducción: Los glucocorticoides se asocian con efectos secundarios graves, relacionados con dosis y tiempo de uso. Desafortunadamente, no existe un método estándar disponible para determinar el nivel de exposición a glucocorticoides en tratamientos prolongados. Objetivo: Crear una aplicación web gratuita y fácil de usar para calcular, de forma sistematizada, la dosis acumulada de glucocorticoides. Métodos: La dosis acumulada se calcula como la suma de todos los períodos de tratamiento con diferentes dosis, y se expresa como la dosis equivalente de prednisona en mg. La dosis durante los períodos en los que la información no está disponible o está incompleta se estima mediante asunciones sistematizadas. Resultados: Un ejercicio de simulación utilizando patrones estándar de uso de esteroides en la polimialgia reumática y la arteritis de células gigantes demostró que, incluso cuando el período de ausencia de información alcanzaba el 50% del tiempo, la precisión de la calculadora tenía un porcentaje de error medio absoluto (MAPE)<7%. Conclusión: Esta herramienta simplifica y estandariza el cálculo de la dosis acumulativa de glucocorticoides, minimizando el sesgo del cálculo.(AU)

Dosificación de ceftriaxona en el paciente crítico hipoproteinémico: un factor más a tener en cuenta / Dosage of ceftriaxone in the critical hypoproteinemic patient: another factor to take into account

Introducción: El objetivo principal del estudio fue evaluar la necesidad de ajuste posológico de ceftriaxona en pacientes críticos hipoproteinémicos. Pacientes y métodos: Estudio observacional y retrospectivo, llevado a cabo en la unidad de cuidados intensivos (UCI) del Hospital General Universitario de Ciudad Real (médico-quirúrgica de 21 camas), en el que se incluyeron pacientes tratados con ceftriaxona en la UCI desde enero de 2014 a diciembre de 2019 y se clasificaron en dos grupos al inicio del tratamiento: pacientes normoproteinémicos (proteínas totales >5,5g/dl) e hipoproteinémicos (proteínas totales ≤5,5g/dl).Variables principales: Edad, sexo, APACHE II, diagnóstico-localización del foco infeccioso, estancia en UCI, dosis de ceftriaxona, pauta posológica, tratamiento antibiótico concomitante, empírico o dirigido, necesidad de cambio de tratamiento, días de antibioterapia y mortalidad. Resultados: Se incluyeron 98 pacientes (44 normoproteinémicos y 54 hipoproteinémicos). No se obtuvieron diferencias estadísticamente significativas entre las características basales de ambos grupos, exceptuando la localización del foco, siendo respiratorio con mayor frecuencia en el grupo de pacientes normoproteinémicos (p=0,044). Se obtuvieron diferencias estadísticamente significativas a favor del grupo de pacientes normoproteinémicos para: estancia en UCI (p=0,001), necesidad de cambio de tratamiento antibiótico (p=0,004), días de antibioterapia (p=0,007) y mortalidad (p=0,046). Conclusión: Los resultados terapéuticos obtenidos en el grupo de pacientes críticos hipoproteinémicos tratados con ceftriaxona ponen en evidencia la necesidad de considerar la hipoproteinemia como un factor que podría condicionar dicho resultado si se emplean las pautas posológicas de tratamiento habituales. (AU)

Introduction: The main objective of the study was to evaluate the need for posologic adjustment of ceftriaxone in critical hypoproteinemic patients. Patients and methods: Observational and retrospective study, carried out in the intensive care unit (ICU) of the General University Hospital of Ciudad Real (21-bed medical-surgical), which included patients treated with ceftriaxone in the ICU from January 2014 to December 2019 and classified into two groups at the beginning of treatment: normoproteinemic (total proteins >5.5 g/dl) and hypoproteinemic (total proteins ≤5.5g/dl) patients.Main variables: Age, sex, APACHE II, diagnosis-location of the infectious site, ICU stay, ceftriaxone dose, dosage regimen, concomitant antibiotic treatment, empirical or targeted antibiotic treatment, need to change treatment, days of antibiotic therapy and mortality. Results: 98 patients were included (44 normoproteinemics and 54 hypoproteinemics).No statistically significant differences were obtained between the basal characteristics of both groups, except for the location of the infectious site, being respiratory more frequently in the group of normoproteinemic patients (p=0.044).Statistically significant differences were obtained in favour of the group of normoproteinemic patients for: stay in ICU (p=0.001), need for change of antibiotic treatment (p=0.004), days of antibiotherapy (p=0.007) and mortality (p=0.046). Conclusion: The therapeutic results obtained in the group of critical hypoproteinemic patients treated with ceftriaxone show the need to consider hypoproteinemia as a factor that could condition such result if the usual treatment dosage guidelines are used.

Frecuencia de consumo inadecuado de vitamina B12 y sus niveles séricos en personas con diabetes mellitus tipo 2 tratadas con metformina en centros de salud de la Provincia de Buenos Aires / Frequency of inadequate consumption of vitamin B12 and its serum levels in people with diabetes mellitus type 2 under metformin treatment in health centers of the Province of Buenos Aires

Introducción: el uso prolongado de metformina y la carencia de consumo de vitamina B12 (B12) pueden provocar su déficit en pacientes con diabetes mellitus tipo 2 (DM2). Objetivos: analizar la frecuencia de consumo insuficiente de B12 según: características personales, datos antropométricos, de laboratorio y uso de metformina; asociar niveles séricos de cobalamina con dosis y tiempo de metformina; establecer la relación entre la ingesta de B12 y los niveles séricos. Materiales y métodos: diseño transversal. Mediante encuesta de frecuencia de consumo de alimentos fuente de B12 en 200 pacientes tratados con metformina por más de 18 meses. Se analizaron datos clínicos, antropométricos, de laboratorio, tiempo y dosis de metformina, en dos centros de salud de la Provincia de Buenos Aires. Resultados: el porcentual de consumo deficiente fue del 29%. Se registró un 47,5% de desocupación que alcanzó un déficit de ingesta del 32,6%. Se midió B12 sérica en el 65% de la muestra y un 53,8% de los valores fue anormal (0,8% en niveles deficientes o bajos y 23% en niveles normal-bajo), observándose asociación significativa a dosis de metformina ≥1.500 mg. Las deficiencias de consumos de B12 (<2,4 µg/día) fueron casi cuatro veces mayores en el grupo con menor recuento eritrocítico (76,9 % vs 18,5%; p<0,00 ). El volumen corpuscular medio (VCM) y el recuento de plaquetas arrojaron datos estadísticamente significativos. Conclusiones: si bien el 29% de la muestra exhibió consumo vitamínico deficiente, el 90% de los pacientes con déficit sérico registró ingestas adecuadas de B12. Dado que se trató de un diseño transversal, donde no pudo evaluarse causalidad, en pacientes intervenidos farmacológicamente con metformina se sugiere considerar su impacto en situaciones deficitarias.

Introduction: the prolonged use of metformin and the lack of consumption of vitamin B12 can cause its deficit, in T2D. Objectives: to analyze the frequency of insufficient consumption of vitamin B12 according to: personal characteristics, anthropometric and laboratory data, and use of metformin; associate serum cobalamin levels with metformin dose and time; establish a relationship between B12 intake and serum levels. Materials and methods: cross-sectional design. Through a survey of the frequency of consumption of food sources of B12 in 200 patients treated with metformin for more than 18 months. Clinical, anthropometric, laboratory data, time and dose of metformin were analyzed in 2 health centers in the Province of Buenos Aires. Results: the percentage of deficient consumption was 29%. 47.5% of unemployment was registered, which reached an intake deficit of 32.6%. Serum B12 was measured in 65% of the sample where 53.8% of values were abnormal (0.8% in deficient levels) and 23% at levels normal lower cut-off point, with a significant association being observed at doses of metformin ≥1,500 mg. Deficiencies in B12 intake (<2.4 µg/day) were almost 4 times higher in the group with the lowest erythrocyte count (76.9% vs 18.5%; p<0.00 ). The MCV and platelet count yielded statistically significant data. Conclusions: although 29% of the sample exhibited poor vitamin intake, 90% of patients with serum deficiency had adequate intakes of vitamin B12. Given that it is a cross-sectional design, where causality cannot be evaluated, it is suggested: in patients undergoing pharmacological intervention with metformin, consider the impact of this in deficient situations.

Sistema personalizado de dosificación (SPD), más allá del blíster: presentación de un caso clínicoen un paciente con enfermedad de Alzheimer / Personalized dosification systems (PDS), beyond the blister: presentation of a clinical case in a patient with Alzheimer’s disease

Los sistemas personalizados de dosificación (SPD) constituyen un recurso primordial para mejorar la adherencia farmacoterapéutica desde la farmacia comunitaria.El farmacéutico comunitario (FC), al ofrecer el SPD como servicio profesional farmacéutico asistencial, debe aprovechar todo su potencial para alcanzar objetivos terapéuticos, además del acondicionamiento de la medicación en el blíster desechable, e incorporar Revisiones del Uso de los Medicamentos (RUM), seguimiento farmacoterapéutico y un contacto frecuente con familia y demás equipo de salud que atienden al paciente. En este caso, conscientes de la importancia de un seguimiento cercano, especialmente durante el confinamiento por la pandemia de COVID-19 y en una paciente con enfermedad de Alzheimer, se consigue mejorar la adherencia terapéutica gracias a un servicio farmacéutico que, más allá del blíster, incluye entrevistas con cuidadora y familia, revisiones del uso de medicación semanales, indicación farmacéutica y contacto directo con el médico de atención primaria (MAP) en situaciones complejas como, por ejemplo: aparición de nuevos problemas de salud y reacciones adversas a los medicamentos (RAM), provocados por medicamentos o dificultad para tragar sólidos. En este caso, debido al aislamiento provocado por el confinamiento, se incluyen además servicios de Atención Farmacéutica Domiciliaria (AFD) y dispensación a domicilio. Protocolizar y realizar una revisión de mediación semanal en el servicio de SPD mejora la adherencia y la consecución de objetivos terapéuticos. La colaboración entre médico, farmacéutico y familia facilita el seguimiento de los pacientes adheridos al servicio para conseguir resultados en salud. (AU)

Evidencia farmacogenética disponible de los subgrupos terapéuticos más consumidos en España / Available pharmacogenetic evidence on the most widely used therapeutic subgroups in Spain

JUSTIFICACIÓN: la variabilidad interindividual en la respuesta a los medicamentos depende de muchos factores, entre los que se encuentra el perfil genético. Polimorfismos en los genes que codifican proteínas implicadas en la farmacocinética y farmacodinámica de los medicamentos pueden modificar su efecto, dando lugar a una respuesta pobre y por lo tanto un tratamiento inefectivo, o una respuesta exagerada lo que conlleva un riesgo alto de toxicidad. La presencia de polimorfismos en genes de transportadores, enzimas metabolizadoras o receptores podría implicar la necesidad o recomendación de un ajuste de dosis, sustitución y/o retirada de los medicamentos. Debido a esto, conocer qué evidencia existe en relación a la farmacogenética de los medicamentos de mayor consumo es de gran interés para los farmacéuticos comunitarios.OBJETIVO: identificar los medicamentos más consumidos en España y determinar la evidencia científica existente en cuanto al efecto que la farmacogenética tiene en ellos.MATERIAL Y MÉTODOS: se identificaron los 15 grupos de medicamentos más consumidos en España (clasificados por subgrupo terapéutico, ACT4) en base al último informe anual disponible de la Prestación Farmacéutica en el Sistema Nacional de Salud (2019).Para cada medicamento de dichos grupos se realizó una búsqueda de la evidencia científica disponible, en materia de farmacogenética, en las Guías Clínicas del CPIC y el DPWG y las anotaciones registradas en la base de datos sobre farmacogenética PharmGKB.RESULTADOS: los 15 subgrupos terapéuticos más dispensados en farmacia comunitaria en España en el 2019 sumaron el 48 % de todos los medicamentos dispensados. De ellos, 8 subgrupos disponen de guías clínicas publicadas de dosificación basada en farmacogenética (Antiulcerosos: inhibidores de la bomba de protones; Hipolipemiantes: inhibidores de la HMG CoA reductasa; Inhibidores de la agregación plaquetaria, excluyendo heparina. (AU)

Evaluation of an enhanced service for medication review in Swiss community pharmacies “Médicaments à Jour?”: study protocol

BACKGROUND: In Switzerland, it is estimated that 20,000 people are hospitalized each year as a result of drug related problems (DRP). There are many sources of DRPs, such as incorrect storage or missing dosages from packages. Community pharmacies (CP) are well positioned to identify and manage such DRPs in a timely manner. In Switzerland, no pharmacy service that focus on the management of DRPs is currently recognized and remunerated. A new service, "Médicaments à Jour?" (MaJ?), has been developed. It is focused on DRPs related to self-medication and medication management at home and it includes a systematic review of the patient’s treatment.OBJECTIVE: To evaluate the impact of the MaJ? service for adults with polypharmacy in Swiss CP for the identification and management of DRPs.METHODS: A pre-post intervention study will be carried out in CPs in the canton of Vaud for 15 months. Volunteer pharmacists will include adults with a prescription for at least four chronic and systemic drugs for at least three months. Trained pharmacists will conduct structured consultations with patients at three points (T0, T6, T12) to deliver the service. The primary outcome of the study is the identification and management of DRPs. Secondary outcomes are patients’ knowledge about their treatments, number of expired or untaken medications and description of pharmaceutical interventions.RESULTS: the study has been approved and will be supported by health authorities ("Direction générale de la santé") and local pharmacists association ("Société Vaudoise de Pharmacie"). The Ethics Committee (CER-VD) concluded that the study does not fall under the Human Research Act. It will begin in spring 2022 in 19-35 pharmacies that will recruit at least 162 patients after randomization of eligible patients through a sequence of computer-generated random numbers. (AU)

Farmacocinética y farmacodinámica de los antibióticos betalactámicos en pacientes críticos / Pharmacokinetics and pharmacodynamics of beta-lactam antibiotics in critically ill patients

La terapia antibiótica óptima en los pacientes en estado crítico puedecomplicarse por la alteración de la fisiología asociada a esta etapa de laenfermedad. La farmacocinética y la exposición a los antibióticos puedenverse alteradas por la enfermedad crítica subyacente y las intervencionesmédicas que reciben estos pacientes en la unidad de cuidados intensivos.Además, las cepas que suelen encontrarse en la unidad de cuidados intensivossuelen ser menos susceptibles y “resistentes” a los antibióticos máshabituales. De hecho, una dosificación de antibióticos que no tenga encuenta estas diferencias únicas, probablemente fracasará y dará lugar aresultados clínicos deficientes y a la aparición de resistencia a los antibióticosen la unidad de cuidados intensivos. Los objetivos de esta revisión sondescribir la farmacocinética de los antibióticos betalactámicos en pacientescríticos, destacar los objetivos farmacocinéticos/farmacodinámicos paralos pacientes y exponer algunas estrategias importantes que pueden optimizarla dosificación de los antibióticos betalactámicos en pacientes críticosen la unidad de cuidados intensivos.

Optimal antibiotic therapy for critically ill patients can be complicated bythe altered physiology associated with critical illness. Antibiotic pharmacokinetics and exposures can be altered driven by the underlying critical illnessand medical interventions that critically ill patients receive in the intensivecare unit. Furthermore, pathogens that are usually isolated in the intensivecare unit are commonly less susceptible and “resistant” to common antibiotics. Indeed, antibiotic dosing that does not consider these unique differences will likely fail leading to poor clinical outcomes and the emergenceof antibiotic resistance in the intensive care unit. The aims of this narrativereview were to describe the pharmacokinetics of beta-lactam antibiotics incritically ill patients, to highlight pharmacokinetic/pharmacodynamic targetsfor both non-critically ill and critically ill patients, and to discuss importantstrategies that can be undertaken to optimize beta-lactam antibiotic dosingfor critically ill patients in the intensive care unit.

Guideline-directed medical therapy in heart failure patients with reduced ejection fraction in Oman: utilization, reasons behind non-prescribing, and dose optimization

Background: Objective: To determine the reasons behind guideline-directed medical therapy (GDMT) non-prescribing, drug utilization before and after excluding those intolerable to GDMT, as well as dose optimization in heart failure (HF) patients with reduced ejection fraction (<40%) (HFrEF) in Oman. Methods: The study included HF patients seen at the medical outpatient clinics at Sultan Qaboos University Hospital, Muscat, Oman, between January 2016 and December 2019 and followed up until the end of June 2021. The use of renin-angiotensin-system (RAS) blockers (angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) or angiotensin receptor-neprilysin inhibitors (ARNIs)), beta blockers and mineralocorticoid receptor antagonists (MRAs) were evaluated as per the European, American, and Canadian HF guidelines. Analyses were performed using univariate statistics. Results: A total of 171 HFrEF patients were enrolled for this study, the overall mean age of the cohort was 63 ± 15 years old and 59% were male. Over 65% of the patients had chronic kidney disease. Almost 55% of the patients were intolerable to GDMT. The proportion of patients on beta blockers, RAS blockers/ hydralazine-isosorbide dinitrate combination, and MRAs, before and after excluding those intolerable to GDMT, were 89%, 97%, and 77%, and, 94%, 47% and 85%, respectively, while the proportion of patients on the GDMT combination concomitantly was 41% and 83%, respectively. A total of 61%, 44% and 100% of the patients were prescribed ≥50% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively, while 19%, 8.2% and 94% of the patients attained 100% of the target dose for beta blockers, RAS blockers/ HYD-ISDN combination and MRAs respectively. (AU)

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.

Antimicrobial defined daily dose in neonatal population / Dosis diaria definida de antimicrobianos en la población neonatal

BackgroundAntimicrobial defined daily dose (DDD), a standardized metric to assess antimicrobial consumption in adult population, has limitations hampering its use in neonatal patients. This study proposes an alternative DDD design applicable for neonates.MethodsNeonates (<1 month-old) from 6 Spanish hospitals during a 12-months period were included. Weight and weeks gestational age of each neonate were the variables collected. DDD (g) for each antimicrobial was calculated by multiplying the obtained weight times the recommended dose (mg/kg) of the antimicrobial for the most common infectious indication selected by the Delphi method.ResultsA total of 4820 neonates were included. Mean age was 36.72 weeks of gestational age and Mean weight was 2.687kg. Standardized DDD (intravenous; oral route) for representative antimicrobials were: Amoxicillin (0.08; 0.08), amoxicillin-clavulanic acid (0.27; 0.08), ampicillin (0.27; x), cloxacillin (0.13; 0.13), penicillin G sodium (0.12), cefazolin (0.13), cefuroxime (0.27; x), cefotaxime (0.27), ceftazidime (0.27), ceftriaxone (0.13), cefepime (0.27) piperacillin-tazobactam (0.54), aztreonam (0.24), azithromycin (0.03; 0.03), clindamycin (0.04; 0.04), amikacin (0.04), gentamicin (0.01), metronidazole (0.04; 0.08), ciprofloxacin (0.04; 0.05), levofloxacin (x;x), fluconazole (0.02; 0.02), itraconazole (0.01; 0.01), fosfomycin (0.27). Restricted antimicrobials: meropenem (0.11), teicoplanin (0.02), vancomycin (0.08; 0.11), linezolid (0.08; 0.08), daptomycin (x), amphotericin B liposomal (0.01).

AntecedentesLa dosis diaria definida de antimicrobianos (DDD), un método estandarizado para evaluar el consumo de antimicrobianos en la población adulta, tiene limitaciones que dificultan su uso en la población neonatal. Este estudio propone un diseño alternativo de la DDD aplicable a los recién nacidos.MétodosSe incluyeron neonatos (<1 mes) de 6 hospitales españoles durante un período de 12 meses. El peso y las semanas de edad gestacional de cada recién nacido fueron las variables recogidas. Las DDD (g) de cada antimicrobiano se calcularon multiplicando el peso obtenido por la dosis recomendada (mg/kg) del antimicrobiano para la indicación infecciosa más común seleccionada por el método Delphi.ResultadosSe incluyeron un total de 4.820 recién nacidos. La edad media fue de 36,72 semanas de edad gestacional y el peso medio fue de 2,687kg. La DDD estandarizado (intravenoso; oral) para antimicrobianos seleccionados fueron: amoxicilina (0,08; 0,08), amoxicilina-ácido clavulánico (0,27; 0,08), ampicilina (0,27; x), cloxacilina (0,13; 0,13), penicilina G sódica (0,12), cefazolina (0,13), cefuroxima (0,27; x), cefotaxima (0,27), ceftazidima (0,27), ceftriaxona (0,13), cefepima (0,27) piperacilina-tazobactam (0,54), aztreonam (0,24), azitromicina (0,03; 0,03) clindamicina (0,04; 0,04), amikacina (0,04), gentamicina (0,01), metronidazol (0,04; 0,08), ciprofloxacina (0,04; 0,05), levofloxacina (x; x), fluconazol (0,02; 0,02), itraconazol (0,01; 0,01), fosfomicina (0,27). Antimicrobianos restringidos: meropenem (0,11), teicoplanina (0,02), vancomicina (0,08; 0,11), linezolid (0,08; 0,08), daptomicina (x), anfotericina B liposomal (0, 01).ConclusionesSe ha diseñado un método útil para la medición de las DDD de antimicrobianos en neonatología para controlar el consumo de antimicrobianos en entornos hospitalarios. Debería validarse en estudios posteriores para incluirse en el diseño de los programas de administración de antimicrobianos neonatales en el futuro.

Efetividade da infusão estendida de Piperacilina-tazobactana - Meropenem no tratamento de pacientes sépticos adultos queimados através da modelagem farmacocinética farmacodinâmica, PK/P / Meropenem and piperacillin/tazobactam by extended infusion and PK/PD approach for drug effectiveness

Introdução: Meropenem (MER) e Piperacilina/Tazobactana (PTZ) são agentes antimicrobianos largamente prescritos para pacientes grandes queimados internados em Unidade de Terapia Intensiva (UTI) com infecções nosocomiais causadas por Gram-negativos sensíveis CIM 2 mg/L, Enterobacteriaceae, EB e Non-enterobacteriaceae, NEB. A síndrome da resposta inflamatória sistêmica (SRIS) que ocorre durante o choque séptico no grande queimado pode causar alteração na farmacocinética do paciente em terapia intensiva, de modo que a dose recomendada pode não atingir o alvo desejado contra Gram-negativos de sensibilidade intermediária CIM >2 mg/L. Objetivo: Investigar a efetividade dos beta-lactâmicos piperacilina e meropenem na infusão estendida comparada à infusão intermitente recomendada, para os pacientes sépticos grandes queimados através da abordagem farmacocinética-farmacodinâmica (PK/PD). Ética, casuística e procedimentos: Autor e co-autores declararam não haver conflito de interesse. O protocolo foi aprovado, registro CAAE 07525118.3.0000.0068. No presente protocolo de estudo investigaram-se 36 pacientes sépticos grandes queimados, ambos os gêneros (12F/24M) em terapia intensiva do choque séptico com piperacilina-tazobactana 4,5g q6h ou meropenem 1g q8h. Os pacientes incluídos foram estratificados em dois grupos com base na administração através da infusão intermitente, 0,5 h (G1) ou da infusão estendida, 3 h (G2), ambos com 16 pacientes cada. Duas amostras sanguíneas (1,5mL/cada) foram coletadas no estado de equilíbrio (Steady State), 3ª e 5ª hora do início da infusão. Os níveis séricos de PTZ e MER foram mensurados através de cromatografia líquida, e a farmacocinética (PK) dos dois grupos de pacientes foi comparada aos dados reportados em voluntários sadios. A abordagem PK/PD foi aplicada para avaliação da cobertura do antimicrobiano a partir da estimativa do índice de predição de efetividade (% fΔT>CIM) e da probabilidade de alcançar o alvo terapêutico (PTA) com base no alvo PK/PD recomendado, 100%fΔT>CIM. Resultados e discussão: As características de admissão dos pacientes G1/G2 foram expressas através de mediana e interquartil: Clcr 115 (90-148) / 127 (90-170) ml/min; 30 (24-31) / 27 (24- 33,5) anos, 70 (61-75) / 71 (65-75) kg, 30 (20-42) / 33,9 (18-38,4)% área total de superfície queimada, SAPS3 53 (45-57) / 48 (37,8-59,5). Na admissão dos pacientes na UTI registrou-se G1/G2: trauma térmico (17/16), trauma elétrico (1/2), lesão inalatória (11/11), ventilação mecânica (16/9) e vasopressores foram necessários em 15/8 pacientes, G1/G2. Ocorreram diferentes alterações na farmacocinética dos dois beta-lactâmicos após a infusão estendida versus a infusão intermitente quando comparadas com dados relatados em voluntários sadios. Evidenciou-se prolongamento da meia vida decorrente do aumento do volume de distribuição. Estes resultados impactaram diferentemente a cobertura. O monitoramento de biomarcadores inflamatórios expressos em medianas (G1/G2) evidenciou aumento do PCR: 232/183mg/L e leucocitose (leucócitos 11/14 mil cel/mm3, neutrófilos 9/10 mil cel/mm3) na fase precoce do choque séptico. Relativamente à microbiologia dos isolados, a erradicação dos patógenos ocorreu para todos os pacientes após a infusão estendida contra Gram-negativos sensíveis (CIM: 2 mg/L), e de sensibilidade intermediária (CIM 4mg/L) como a K. pneumoniae e P. aeruginosa, enquanto a infusão intermitente garantiu erradicação de patógenos apenas até CIM 2 mg/L. Conclusão: Evidenciou-se a superioridade da infusão estendida frente à infusão intermitente na cobertura dos dois antimicrobianos, no alvo terapêutico considerado 100%fΔT>CIM. Registraram-se alterações na farmacocinética destes agentes nos pacientes frente aos dados reportados para voluntários sadios. Diferença significativa entre grupos (G1/G2) foi encontrada com relação meia vida biológica, e ao volume de distribuição tanto pata a piperacilina quanto para o meropenem

Background: Meropenem (MER) and Piperacillin/Tazobactam (PTZ), antimicrobial betalactam agents are widely prescribed to burn patients from the Intensive Care Unit (ICU) with nosocomial infections caused by Gram-negative strains. Change in the pharmacokinetics of critically ill patient occurs during the systemic inflammatory response syndrome (SIRS) at the course of septic shock. Then, the recommended dose administered by intermittent infusion, 0.5 hr cannot reach the target against gram-negative strains MIC > 2 mg/L. Subject: To investigate drug effectiveness of the beta-lactams piperacilin and meropenem in extended infusion compared to the recommended intermittent infusion in critically ill septic burn patients using pharmacokinetic-pharmacodynamic (PK/PD) approach. Ethics, Casuistry and Methods: All authors declared there is no conflict of interests. Ethical approval CAAE, register 07525118.3.0000.0068. It was investigated in the study protocol 36 septic burn patients of both genders (12M / 24F), undergoing antimicrobial therapy with PTZ 4.5 g q6h or MER 1g q8h. Based on the chosen antimicrobial therapy and drug infusion prescribed by the physician, patients were stratified in groups with intermittent 0.5h infusion (G1) or with the extended 3h infusion (G2), both groups with 16 patients each. Two blood samples were collected at the steady state (1.5mL / each), at the 3rd and 5th hrs of starting the infusion. Serum levels were measured by liquid chromatography. Pharmacokinetics (PK) of MER or PTZ was compared to data reported in healthy volunteers for both groups of patients. PK/PD approach was applied to estimate the drug effectiveness index (fΔT> MIC) and to assess the probability of target attained (PTA) based on the recommended PK/PD target, 100% fΔT> MIC. Results and discussion: Characteristics of patients admission G1/G2 were: Clcr 115(90- 148)/127(90-170) ml/min; 30(24-31)/27(24-34) yrs, 70(61-75)/71(65-75) kg, 30(20- 42)/33.9(18-38.4)% total burn surface area, SAPS3 53(45-57)/48(37.8-59.5), medians (interquartile): thermal trauma occurred (17/16), electric trauma (1/2), inhalation injury (11/11), mechanical ventilation (9/16) and vasopressors required in 15/8 patients. It was demonstrated that different PK changes occurred for both beta-lactam agents after the extended or intermittent infusion by comparison with data reported in healthy volunteers. PK changes were related to the prolongation of biological half-life and increases on volume of distribution with impact on pharmacodynamics. On the other hand, meropenem total body clearance reduced by 50% at the earlier period of septic shock could be explained by the reduction of MER-transporters expression in the tubular renal secretion, once only patients with renal function preserved were included in the study protocol. Inflammatory biomarkers increased at the earlier period of septic shock: C-rp 232/183mg/L; leukocytes 11/14*103cel/mm3, neutrophils 9/10*103cel/mm3, medians, G1/G2. Clinical and microbiological cure was obtained for all patients of G1 against MIC < 2mg/L after intermittent 0.5 h infusion; while PK/PD target was attained for G2 patients undergoing antimicrobial therapy with MER or PTZ by extended infusion against gram negative strains K. pneumoniae, P. aeruginosa up to MIC 4mg L. Conclusion: Superiority of the extended infusion over intermitent infusion was obtained for the two antimicrobials was evidenced, in the therapeutic target considered 100%fΔT>CIM. Changes in the pharmacokinetics of these agents were recorded in patients compared to data reported for healthy volunteers. A significant difference between groups (G1/G2) was found in relation to biological half-life and volume of distribution for both piperacillin and meropenem

In vitro anti-inflammatory, anti-arthritic and anti- proliferative activity of green synthesized silver nanoparticles - Phoenix dactylifera (Rothan dates)

Abstract Traditionally dates is consumed as a rich source of iron supplement and the current research discuss the synthesis of silver nanoparticles (AgNPs) using methanolic seed extract of Rothan date and its application over in vitro anti-arthritic, anti-inflammatory and antiproliferative activity against lung cancer cell line (A549). FTIR result of synthesised AgNPs reveals the presence of functional group OH as capping agent. XRD pattern confirms the crystalline nature of the AgNPs with peaks at 38º, 44º, 64º and 81º, indexed by (111), (200), (220) and (222) in the 2θ range of 10-90, indicating the face centered cubic (fcc) structure of metallic Ag. HR- TEM results confirm the morphology of AgNPs as almost spherical with high surface areas and average size of 42 ± 9nm. EDX spectra confirmed that Ag is only the major element present and the Dynamic light scattering (DLS) assisted that the Z-average size was 203nm and 1.0 of PdI value. Zeta potential showed − 26.5mv with a single peak. The results of the biological activities of AgNPs exhibited dose dependent activity with 68.44% for arthritic, antiinflammatory with 63.32% inhibition and anti-proliferative activity illustrated IC50 value of 59.66 µg/mL expressing the potential of AgNPs to combat cancer

A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

Potential health risks surrounding ingredients of pre-workout and post-workout dietary supplements: a thorough label analysis / Potenciais riscos de saúde relacionados com ingredientes de suplementos alimentares de pré-treino e pós-treino: análise meticulosa de rótulos

ABSTRACT Objective Dietary supplements use is increasing. Dietary supplements may contain high doses of substances or dangerous ingredient combinations. This article aims to investigate, by analyzing dietary supplements labels, if there are any doping substances or dangerous amounts of any other component in the reviewed dietary supplements. Methods Several brands which possessed their supplements sorted in pre-workout and post-workout were analyzed. 40 dietary supplements with all ingredients described were included. The minimum and maximum dosages of dietary supplements were statistically described as Mean±SD. Results Citrus aurantium extract, Yohimbe extract, Garcinia cambogia extract and Maca root extract were reported in some of the analyzed dietary supplements. Regarding caffeine, the pre-workout group displayed higher mean caffeine (241±86mg) than the post-workout group (183±68mg), and the minimal mean dose was 226±84mg; meanwhile, the maximal mean dose was 242±88mg. Concerning creatine, the pre-workout group displayed lower mean creatine (3106±1079mg) than the post-workout group (4137±4177mg), and the minimal mean dose was 3167±1728mg; meanwhile, the maximal mean dose was 3917±3643mg. The salt content in the post-workout group displayed a much higher mean (2155±4486mg) than the pre-workout group (464±605mg), and the minimal mean dose was 1635±3930mg; meanwhile, the maximal mean dose was 1708±3926g. Conclusions No doping substances were reported in the dietary supplements, but consumption recommendations on the label could lead to excessive consumption of some not yet fully tested ingredients.

RESUMO Objetivo O uso de suplementos alimentares está a aumentar. Estes podem conter altas doses de substâncias ou combinações de ingredientes perigosas. Este artigo procura encontrar, analisando os rótulos dos produtos, se existem substâncias dopantes ou nocivas. Métodos Foram analisadas várias marcas cujos respectivos suplementos foram classificados em pré e pós-treino. Foram incluídos 40 suplementos com todos os ingredientes descritos. A respectiva dose mínima e máxima foi descrita estatisticamente como média ± DP. Resultados Extratos de Citrus aurantium, Yohimbe, Garcinia cambogia e raiz de Maca foram encontrados nos suplementos analisados. O grupo pré-treino apresentou maior média de cafeína (241±86mg) do que o grupo pós-treino (183±68mg), e a dose média mínima foi de 226±84mg, enquanto a dose média máxima foi de 242±88 mg. O grupo pré-treino apresentou menor média de creatina (3106±1079mg) do que o grupo pós-treino (4137±4177mg), e a dose média mínima foi de 3167±1728mg, enquanto a dose média máxima foi de 3917±3643mg. O grupo pós-treino apresentou uma maior média de sal (2155±4486mg) do que o grupo pré-treino (464±605mg), e a dose média mínima foi 1635±3930mg, enquanto a dose média máxima foi de 1708±3926mg. Conclusão Não foram encontradas substâncias dopantes nos suplementos, mas algumas recomendações de consumo nos rótulos poderão levar à sobredose de certos ingredientes menos testados.

Performance of the allometric power model in scaling from adult to paediatric antiretroviral dose in children at a Referral Hospital in Windhoek, Namibia

Background: World Health Organization (WHO) advocates use of weight bands in antiretroviral therapy (ART) guidelines. Allometric scaling could be a more reliable method because it uses a non-linear approach in relating dose to body weight. This study evaluates performance of the allometric ¾ power model in comparison to WHO weight band method in children receiving ART. Methods: Records of children receiving (ABC/3TC) + DTG were reviewed. Paediatric ABC/3TC dose was calculated from the adult dose using the allometric ¾ power model and compared to WHO weight band dose. Results: WHO weight band strategy grouped 50.6% of the children in the 25 kg category and therefore received the adult dose of ABC/3TC (600 mg/300 mg); only 1.1% received this dose with allometric scaling. Mean dose (3.8 tablets) for the WHO weight band dosing method was found to be significantly higher (p<0.0001) than for allometric scaling (1.5 tablets). Conclusions: WHO weight bands may result in the 25 kg weight category receiving a much higher dose leading to ADRs. Using allometric scaling, we recommend a weight band strategy that could improve paediatric ABC/3TC dosing

Assessment of Adult's Abdominopelvic Computed Tomography Radiation Doses in Amhara Region, Ethiopia

BACKGROUND: Computed Tomography plays a priceless role for diagnostic and therapeutic purpose; however,applying an optimized Computed Tomography Technique to produce qualified image while delivering minimum radiation dose to patients is the common challenge. The main objective of this study was to establish local diagnostic reference levels for adult patients who visited abdominopelvic Computed Tomography examination. METHODS: A total of 158 patients who had taken abdominopelvic Computed Tomography examination from three selectedAmhara region hospitals were investigated. Both prospective and retrospective techniques of data collection were used while collecting the data in the entire sample. Two GE - Optima Computed Tomography 540 (16 slices) and one Phillips ­ Brilliance (64slices), were employed during data collections. Data for patient demographics scan protocols, Computed Tomography dose descriptors and machine specifications were collected and analyzed by using SPSS software version 26. RESULTS: The third quartile estimated computed tomography dose index volume and dose length product, which is the local Diagnostic Reference Levels, were 12 mGy and 1904 cm.mGy respectively. The investigated local Diagnostic Reference Levels of Computed Tomography Dose index volume (mGy) was comparable to other international Diagnostic Reference Levels. However, the third quartile value of dose length product (cm.mGy) was higher than other reported international Diagnostic Reference Levels. CONCLUSION: The values of local Diagnostic Reference Levels presented in this work can be used as a baseline upon which future dose measurements can be compared in Amhara region

Pharmaceutical evaluation of compounded furosemide capsules and excipient performance

Abstract Compounding pharmacies play an important role not only in compounding personalized formulations, but also preparing drugs at the same concentration and dosage as those from commercial manufacturers. The excipients used in compounding are generally standardized for many drugs, however they do not consider the intrinsic properties, such as the poor water solubility, of each substance. The excipient performance of commercially available compounded furosemide capsules in 7 compounding pharmacies from Manaus was evaluated and compared them to the performance of the reference medicinal product (Lasix® tablets) and 2 batches of capsules made in-house (T2 and T4) with a standardized excipient. All batches were subjected to tests for weight variation, assay, uniformity of dosage units, disintegration and dissolution profile. Of the 7 different compound formulas acquired in the compounding pharmacies, only 2 passed all tests. Most formulas passed the tests for weight determination, disintegration time and assay, however batches from 2 establishments failed in regards to the uniformity of the content and 5 batches failed the dissolution test. The reference medicinal product was approved in all tests, as were the T2 capsules made in-house with drug-excipient ratio 1:2. These results confirm the importance of the excipient composition, especially for poorly soluble drugs.