Use of antimicrobials in pediatric wards of five Brazilian hospitals.

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Adverse Drug Reactions to Anti-infectives in Hospitalized Children: A Multicenter Study in Brazil.

INTRODUCTION: Adverse drug reactions (ADRs) to anti-infectives affect especially hospitalized children and contribute to increased morbidity, mortality, length of stay, and costs in healthcare systems. OBJECTIVE: To assess ADRs associated with anti-infective use in Brazilian hospitalized children. METHODS: A prospective cohort study was conducted in 5 public hospitals over 6 months. Children aged 0-11 years and 11 months who were hospitalized for more than 48 h and prescribed anti-infectives for over 24 h were included. RESULTS: A total of 1020 patients met the inclusion criteria. Of these, 152 patients experienced 183 suspected ADRs. Most reactions were related to the gastrointestinal system (65.6%), followed by skin reactions (18.6%). Most reactions were classified as probable causality (58.5%), moderate severity (61.1%), and unavoidable (56.2%). Our findings showed that ADRs were associated with increased length of stay (P < .001), increased length of therapy (P < .015), increased days of therapy (P = .038), and increased number of anti-infectives prescribed per patient (P < .001). CONCLUSION: Almost 15% of hospitalized children exposed to anti-infectives presented suspected ADRs. Their occurrence was classified as probable, of moderate severity, and unavoidable. ADRs were significantly influenced by the length of hospital stay and the number of anti-infectives prescribed per patient.

Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children.

BACKGROUND: Children are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools-Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)-to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children. METHODS: The validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach's alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval. RESULTS: There was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach's alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67-0.97) and 0.68 (0.45-0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children. CONCLUSION: The methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer. TRIAL REGISTRATION: This study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira - Federal University of Rio de Janeiro - Number: 3.264.238.

Structural and thermal analyses of zinc and lactose in homeopathic triturated systems.

BACKGROUND: A series of different experimental approaches was applied in Zincum metallicum (Zinc met.) samples and lactose controls. Experiments were designed to elucidate the effect of zinc trituration and dynamization on physicochemical properties of homeopathic formulations, using lactose as excipient. METHODS: Zinc met. potencies (Zinc met 1-3c) were triturated and dynamized using lactose as excipient, according to Brazilian Homeopathic Pharmacopoeia. Lactose samples (LAC 1-3c) were also prepared following the same protocol and used as controls. The samples were analyzed structurally by Atomic Absorption Spectroscopy (AAS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM) with Energy Dispersive X-ray Spectroscopy (EDX) and Scanning Electron Microscopy (SEM), and thermodynamically by Thermogravimetry (TG) and Differential Scanning Calorimetry (DSC). RESULTS: AAS analysis detected 97.0 % of zinc in the raw material, 0.75 % (Zinc met 1c) and 0.02% (Zinc met 2c). XRD analysis showed that inter-atomic crystalline spacing of lactose was not modified by dynamization. Amorphous and crystalline lactose spheres and particles, respectively, were observed by TEM in all samples, with mean size from 200 to 800 nm. EDX obtained with TEM identified zinc presence throughout the amorphous matter but individualized zinc particles were not observed. SEM images obtained from dynamized samples (LAC 1c and Zinc met 1c) with electron backscattering could not identify zinc metal grains. The dynamization process induced Derivatives of Thermal Gravimetric (DTg) peak modification, which was previously centered near 158°C to lactose, to a range from 140 to 170°C, suggesting the dynamization process modifies the temperature range of water aggregation. Thermal phenomena were analyzed and visualized by Analysis of Variance (ANOVA) and Principal Component Analysis (PCA) statistics. Both indicated that fusion enthalpy of dynamized samples (DynLAC 1-3c; DynZn 1-3c) increased 30.68 J/g in comparison to non-dynamized lactose (LAC; p < 0.05). CONCLUSIONS: Our results suggested no structural changes due to the trituration and dynamization process. However, TG and DSC analyses permit the differentiation of dynamized and non-dynamized groups, suggesting the dynamization process induced a significant increase in the degradation heat. These results call for further calorimetric studies with other homeopathic dilutions and other methodologies, to better understand the dynamics of these systems.