Inappropriate Doses of Intravenous Polymyxin B after Renal Adjustment Lead to Treatment Failure

Sub-therapeutic doses, shorter duration of therapy, female gender, bacteremia, and renal impairment were among independent predictors of polymyxin B treatment failure. In this study, we found an association between inappropriate doses of polymyxin B (<15000 or >25000 unit/kg/day) and renal impairment. Inappropriate doses of polymyxin B were significantly associated with CrCl 20-50 mL/min (p = 0.021, ORadj 6.660, 95% CI 1.326, 33.453) and CrCl <20 mL/min (p = 0.001, ORadj 22.200, 95% CI 3.481, 141.592). By conducting sub-group analysis only using subjects with appropriate dosage, renal impairment was not associated with polymyxin B treatment failure, thus indicating that treatment failure was due to an inappropriate dose of polymyxin B, rather than renal impairment. In conclusion, renal impairment was not directly associated with treatment failure but was due to an inappropriate dosage of polymyxin B after renal adjustment

Retrospective evaluation and prediction of clearance and toxicity of high dose methotrexate in childhood acute lymphoblastic leukemia patients

To find the predictors of High Dose Methotrexate toxicities in childhood Acute Lymphoblastic Leukemia Patients. This study included 198 Childhood Acute Lymphoblastic Leukemia patients (303 infusions) who were treated with High Dose Methotrexate. Methotrexate levels at different time point were measured by modified enzyme multiplied immunoassay technique assay. The correlation between Methotrexate levels and toxicity was evaluated by Receiver Operating Characteristic curve. When the Methotrexate level at 42 h was lower than 0.76 µmol/L, the sensitivity for predicting thorough clearance at 66 h was 90.78%. When the Methotrexate level at 42 h was higher than1.5 µmol/L, the sensitivity for predicting delayed clearance was 82.17%. When the Methotrexate level at 66 h was higher than 0.5 µmol/L, the sensitivity for predicting Methotrexate toxicity was 89.09%. When the Methotrexate level at 66 h was lower than 0.1 µmol/L, the sensitivity for predicting Methotrexate nontoxicity was 92.73%. The Methotrexate level at 42 h could be predictor for delayed clearance. The Methotrexate level at 66 h could be predictor for toxicity.

New flavonoid with antidiabetic and antioxidant potential from Tetrastigma angustifolia (Roxb. ) Deb leaves

Ethnomedicinal survey documents the traditional practices of Tetrastigma angustifolia leaves in the management of diabetes in the North-eastern region of India. The present study was aimed at isolation of possible antidiabetic principle(s) from T. angustifolia leaves and evaluation of antidiabetic efficacy of isolated compound(s) in experimental animal model. The methanolic extract of T. angustifolia leaves was obtained by Soxhlet extraction method and subjected to silica gel column chromatography (100-200 mesh). Fraction 18-176 chloroform:methanol (70:30) yielded a pale yellow colored compound. The structure of pure compound was elucidated with the help of UV, IR, NMR and Mass spectrometric/techniques. The antioxidant activity of the isolated compound was evaluated in vitro by various radical scavenfing assay methods.. Oral acute toxicity study was carried out according to OECD guideline 423 in Wistar rats. The antidiabetic efficacy of the isolated compound was evaluated in STZ-induced diabetic rats at the dose of 5 mg/kg b.w. for duration of 21 days. The present study reports a new flavocnoid compound isolated from the methanolic extract of T. angustifolia leaves and identified as 8-hydroxyapigenin 7-O-D-glucopyranoside. The flavonoid compound exhibited potent antidiabetic (hypoglicemic) activity in STZ-induced diabetic rats with promising antioxidant (radical scavenging activity) potential in vitro.

Nonadherence to treatment recommendations is a factor contributing to the clinical failure of daptomycin: Cohort study in Brazil

To evaluate the clinical outcomes of daptomycin therapy and adherence to treatment recommendations, a retrospective cohort study was conducted with patients that received daptomycin during the period of the study. The adherence and nonadherence to clinical guidelines were assessed through organism identification, dose and time of treatment, management of bacteremia, and vancomycin treatment failure. A multiple logistic regression model analyzed the association between independent variables and clinical success (dependent variable), considering 5% of statistical significance. The study presented 52 patients who received daptomycin for the treatment of bacteremia (21.1%) or infections (osteomyelitis [63.5%], synovial fluid [15.4%]). Most patients (86.5%) received daptomycin as the second line of treatment, and 51.9% achieved clinical success. The patients had a better chance of clinical success when they followed the guideline indications (OR = 16.86; 95% CI = 1.45-195.88) and the medication was prescribed by a specialist in infectious diseases (OR = 4.84; 95% CI = 1.11-21.09). The study demonstrated lower clinical success than that described in the literature because of patients who were not eligible according to the clinical guidelines. Adherence to recommendations and appropriate prescription of reserve antibiotics is important in limiting early resistance, and avoiding clinical failure and unnecessary expenditure.

Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Effect of prodigiosin on the alleviation of the intestinal inflammation of weaned rats based on 1H-NMR spectroscopy study and biochemistry indexes

Weaning results in intestinal dysfunction, mucosal atrophy, transient anorexia, and intestinal barrier defects. In this study, the effect of prodigiosin (PG) on the intestinal inflammation of weaned rats was investigated by using 1H-NMR spectroscopy and biochemistry indexes to regulate the intestinal metabolism. After administration for 14 days, the body mass of the PG group was increased by 1.29- and 1.26-fold compared with those of the control and alcohol groups, respectively, using a dose of 200 µg PG·kg-1 body weight per day. PG increased organic acid content and decreased moisture, pH values, and free ammonia in feces. In addition, PG alleviated the intestinal inflammation of weaned rats. The analysis of 1H-NMR signal peak attribution and the model validation of metabolic data of feces contents showed that PG significantly affected the metabolism of small molecular compounds in the intestinal tract of weaned rats. This study presents the promising alternative of using PG to alleviate intestinal inflammation effectively in the intestinal tract of weaned rats.

Uso inadequado de organofosforados: uma prática de risco para bovinos no Sul do Rio Grande do Sul / Misuse of organophosphate: potential risk to cattle in Southern Brazil

Com o objetivo de determinar as causas para o súbito aumento no número de surtos de intoxicação por organofosforados foram analisados nove surtos da intoxicação diagnosticados em bovinos no Laboratório Regional de Diagnóstico da Faculdade de Veterinária da Universidade Federal de Pelotas (LRD/UFPel) entre novembro de 2013 e fevereiro de 2014. Em todos os surtos os animais foram tratados com concentrações entre duas e 151 vezes maiores que a concentração recomendada de diazinon para banho carrapaticida utilizado nas diferentes propriedades. Contribuíram, ainda, para o grande número de casos de intoxicação a via de adminstração pour on não recomendada para os produtos utilizados e o intenso calor registrado na época de ocorrência dos surtos.

In order to determine the cause of the sudden increase in the number of outbreaks of organophosphate poisoning, nine outbreaks diagnosed in cattle were analyzed at the Laboratório Regional de Diagnóstico, Faculdade de Veterinária, Universidade Federal de Pelotas (LRD/UFPel) between November 2013 and February 2014. In all outbreaks the animals were treated with concentration from two to 151 times higher than the concentration recommended of diazinon for tick treatment. The incorrect route of application, and the intense heat recorded at the time of the outbreaks also contributed to the large number of poisoning.

Clinical pharmacist evaluation of medication inappropriateness in the emergency department of a teaching hospital in Malta / Evaluación del farmacéutico clínico sobre la inadecuación de la medicación en un servicio de urgencias de un hospital universitario en Malta

Appropriate prescribing remains an important priority in all medical areas of practice. Objective: The objective of this study was to apply a Medication Appropriateness Index (MAI) to identify issues of inappropriate prescribing amongst patients admitted from the Emergency Department (ED). Method: This study was carried out at Malta’s general hospital on 125 patients following a twoweek pilot period on 10 patients. Patients aged 18 years and over and on medication therapy were included. Medication treatment for inappropriateness was assessed by using the MAI. Under-prescribing was also screened for. Results: Treatment charts of 125 patients, including 697 medications, were assessed using a MAI. Overall, 115 (92%) patients had one or more medications with one or more MAI criteria rated as inappropriate, giving a total of 384 (55.1%) medications prescribed inappropriately. The mean SD MAI score per drug was 1.78 (SD=2.19). The most common medication classes with appropriateness problems were supplements (20.1%), antibiotics (20.0%) and steroids (19.8%). The most common problems involved incorrect directions (26%) and incorrect dosages (18.5%). There were 36 omitted medications with untreated indications. Conclusion: There is considerable inappropriate prescribing which could have significant negative effects regarding patient care (AU)

La prescripción adecuada es una prioridad importante en todas las áreas de la práctica médica. Objetivo: El objetivo de este estudio fue aplicar el Medication Appropriateness Index (MAI) para identificar problemas de prescripción de medicación inadecuada entre los pacientes admitidos en un servicio de urgencias (ED). Método: Este estudio se realizó en el Hospital General de Malta sobre 125 pacientes después de un periodo piloto de dos semanas sobre 10 pacientes. Se incluyeron pacientes de 18 o más años con medicación. La inadecuación del tratamiento se evaluó usando el MAI. También se evaluó la sub-prescripción. Resultados: Los perfiles de medicación de los 125 pacientes, que incluían 697 medicamentos, se evaluaron con el MAI. En general, 115 pacientes (92%) tenían uno o más medicamentos con uno o más de los criterios del MAI evaluados como inadecuados, dando un total de 384 (55,1%) medicamentos prescritos inadecuadamente. La media (SD) de puntuación del MAI por medicamento fue de 1,78 (SD=2,19). Los grupos terapéuticos más comúnmente asociados a problemas de inadecuación eran los suplementos (20,1%), antibióticos (20,0%) y corticoides (19,8%). Los problemas más comunes incluían indicaciones incorrectas (26%) y dosis incorrectas (18,5%). Hubo 36 medicaciones omitidas con indicaciones no tratadas. Conclusión: Hay una considerable prescripción de medicación inadecuada que podría tener significativos efectos negativos en los cuidados del paciente (AU)

¿Cómo hacer buen uso del metotrexato en artritis reumatoide? / How to effectively use methotrexate in rheumatoid arthritis?

El metotrexato (MTX) es el fármaco modificador de la enfermedad de primera elección en artritis reumatoide. A pesar del uso casi generalizado por reumatólogos en todo el mundo, hay mucha discordancia entre la forma de iniciar la dosis, la vía de administración y la forma de realizar el incremento de dosis. En este artículo se planteamos un esquema simplificado del uso de este fármaco a individualizar en cada caso, basado en los aspectos farmacológicos, guías y protocolos de manejo publicados en revistas de impacto de nuestra especialidad en los últimos años. Se revisa además las reacciones adversas y efectos secundarios y cómo realizar el seguimiento de éstos (AU)

Methotrexate (MTX) is the first choice disease modifying anti-rheumatic drugs for rheumatoid arthritis. In spite of its generalized use by rheumatologists worldwide, there is a general lack of agreement regarding the route of administration, the start-up dose and the way to increase the same. In this article we propose a simplified outline for the use of the drug that should be individualized, based on it's pharmacological aspects, guidelines and recommendations published in high impact factor journals during the past few years. Adverse reactions and side effects, as well as their follow up are also reviewed (AU)

Preparo e administração de medicamentos intravenosos pela enfermagem: garantindo a segurança junto aos pacientes críticos / Preparation and administration of intravenous drugs by nursing: ensuring the safety of critical patients

O objeto de estudo é o preparo e a administração de medicamentos pela enfermagem por via intravenosa. O objetivo geral foi discutir as consequências, para os pacientes, dos erros encontrados a partir do preparo e da administração de medicações de uso intravenoso pela enfermagem, no ambiente hospitalar. Os objetivos específicos foram determinar os grupos medicamentosos e os medicamentos envolvidos em erros; e identificar o tipo e frequência desses erros que ocorrem no preparo e administração de medicamentos intravenosos pela enfermagem. Trata-se de uma pesquisa com desenho transversal de natureza observacional, sem modelo de intervenção. Foi desenvolvida em um hospital público, da rede sentinela, do Rio de Janeiro onde foram observados técnicos de enfermagem preparando e administrando medicamentos intravenosos, em três setores: Unidade de Terapia Intensiva, Clínica Médica e Clínica Cirúrgica. Foram observadas 367 doses preparadas e 365 doses administradas, totalizado 732 doses, à luz de 14 categorias. Para cada dose observada havia somente duas possibilidades: certo ou errado. Com relação ao perfil das medicações, os grupos prevalentes foram os antimicrobianos com 176 doses (24,04%), seguidos dos antissecretores com 149 doses (20,36%) e analgésicos com 126 doses (17,21%). Anestésicos e anticonvulsivantes foram os menos observados. Todas as categorias foram divididas em dois grupos: os com potencial de dano para o paciente e os com potencial para alterar a resposta terapêutica do medicamento. Na etapa do preparo, no grupo com potencial de dano, as categorias foram: “não troca as agulhas” com 88,77% de erro; “não desinfecção de ampolas” (80,27%) e “não faz limpeza de bancada” (77,26%). Nas categorias “não usa máscara” e “não identifica o medicamento”, não foram encontrado erros. Para o grupo com potencial para alterar a resposta terapêutica, as categorias foram: “hora errada” (57,26%) e “dose errada” (6,58%)...

The overall objective was to discuss the consequences for patients about the found errors from the intravenous medications preparation and administration by nurses in the hospital. The specific objectives were to determine the errors referring to involved drugs, their groups, type, and frequency in the intravenous medications preparation and administration by nurses. This is a survey of cross-sectional observational, without intervention model. It was developed in a public hospital, belonging to the sentinel network of Rio de Janeiro, where nursing technician were observed, preparing and administering intravenous medicines in three sectors: the Intensive Care Unit, Medical Clinic, and Surgical Clinic. There were observed 367 prepared doses and 365 administered, totaling 732 in the light of 14 categories. For each observed dose, there were only two possibilities, right or wrong. Regarding to the medication profile, the prevalent groups were antimicrobials with 176 doses (24.04%), followed by antisecretory medicines with 149 doses (20.36%), and analgesics with 126 doses (17.21%). Anesthetics and anticonvulsants were the least observed. All categories were divided into two groups: those with damage potential to the patient and others with potential to alter the drug therapeutic response. In the preparation stage, in the group with the damage potential, the categories were "do not exchange needles" with 88.77% of error, "no disinfection of ampoules” (80.27%), and "do not clean bench" (77.26%). In the categories "not wearing a mask" and "do not identify the drug”, no errors were found. For the group with potential to alter the therapeutic response, the categories were "wrong time" (57.26%) and "wrong dose" (6.58%)...