Estudio del uso de medicamentos con indicación off-label en pacientes pediátricos intrahospitalarios en una clínica de tercer nivel de la ciudad de Barranquilla / Study of the use of medications with off-label indication in pediatric patients intrahospital in a third level clinic in the city of Barranquilla

Objetivo: Estudiar el uso de los medicamentos con indicaciones off-label en pediatría intrahospitalarios en una clínica de tercer nivel de la ciudad de Barranquilla-Atlántico. Metodología: El diseño empleado en este estudio fue observacional, donde se obtuvo la frecuencia de las prescripciones y administración de los medicamentos con indicación no aprobada. El estudio se realizó en cuatro fases, la primera fue la búsqueda sistemática de medicamentos basados en la literatura científica, en la segunda fase se seleccionaron los pacientes basados en los criterios de inclusión del estudio, la tercera fase se realizó el análisis y procesamiento de los datos y la cuarta fase fue la construcción del listado de medicamentos off-label Resultados: Se realizó un seguimiento a 204 pacientes de los pabellones Caribe y UCI Pediátrica, que cumplieran con los criterios de inclusión, durante el periodo de tres meses de estudio. Se identificaron 386 medicamentos con indicación off-Label en 765 prescripciones durante el periodo de estudio, identificándose al menos un medicamento prescrito con uso no incluido o indicación off-label. Según su acrónimo a nivel de la clasificación ATC, los pertenecientes a los tres niveles o grupos más destacados fueron los pertenecientes al grupo J con un 26,94%, grupo N 20,98% y el grupo C con un 16,68% de las prescripciones. Conclusiones: El mayor porcentaje de la población durante el periodo de estudio fue el primer año de vida. Los medicamentos con mayor número de prescripciones fueron el meropenem, la dipirona, salbutamol, espironolactona, enalapril, bromuro de ipatropio, la gentamicina, caspofungina, propanolol y tramadol. (AU)

Objective: To study the use of drugs with off-label indications in in-hospital pediatric patients in a third-level Clinic in the city of Barranquilla-Atlántico. Methodology: The design used in this study was observational, where the frequency of prescriptions and administration of drugs with an unapproved indication was obtained. The study was carried out in four phases, the first was the systematic search for drugs based on the scientific literature, in the second phase the patients were selected based on the inclusion criteria of the study, the third phase was the analysis and processing of the data and the fourth phase was the construction of the list of off-label drugs. Results: 204 patients from the Caribe and Pediatric ICU wards, who met the inclusion criteria, were followed during the three (3) month study period. 386 drugs with off-label indication were identified in 765 prescriptions during the study period, identifying at least one drug prescribed with use not included or off-label indication. According to its acronym at the level of the ATC classification, those belonging to the three most prominent levels or groups were those belonging to group J with 26.94%, group N 20.98% and group C with 16.68% of the prescriptions. Conclusions: The highest percentage of the population during the study period was the first year of life. The medications with the highest number of prescriptions were meropenem, dipyrone, salbutamol, spironolactone, enalapril, ipatropium bromide, gentamicin, caspofungin, propanolol and tramadol. (AU)

Origin and population structure of Brazilian hair sheep breeds.

Brazilian hair sheep constitute a genetic diversity hotspot. These animals are found in the harsh environments of the Brazilian Northwest (semi-arid) region. Genotypes (50K SNP chip) from seven Brazilian sheep breeds (five hair and two coarse wool types) and 87 worldwide breeds were used to test for population structure, admixture and genetic diversity. Moreover, phylogenetic trees evaluating migration events between genetic groups were built. Brazilian Somali, a fat-tailed breed, had a close relationship with East African breeds and clustered distinctly from other Brazilian breeds. Brazilian Blackbelly and Barbados Blackbelly had a close relationship. The Morada Nova breed did not show close relationships with European or African breeds, revealing a single migration event from an Algerian hair breed. Brazilian Fat-tail and Morada Nova share a common ancestor, but the former showed introgressions from Brazilian Somali and Afrikaner breeds, explaining the fat-tail phenotype. The Santa Inês breed received a substantial contribution from Brazilian Bergamasca and showed an admixed origin with recent introgressions from other breeds, mainly from Suffolk. Furthermore, Brazilian Somali and Brazilian Fat-tail are the most endangered sheep genetic resources in Brazil and should be the focus for ex situ conservation programs. In conclusion, Brazilian hair sheep show an African origin and are characterized by diverse genetic composition, reinforcing the need for conservation of these genetic resources, and at the same time, this highly diverse group has variability that can be used in breeding programs.

The interplay between autophagy and apoptosis mediates toxicity triggered by synthetic cathinones in human kidney cells.

Synthetic cathinones abuse remains a serious public health problem. Kidney injury has been reported in intoxications associated with synthetic cathinones, but the molecular mechanisms involved have not been explored yet. In this study, the potential in vitro nephrotoxic effects of four commonly abused cathinone derivatives, namely pentedrone, 3,4-dimethylmethcatinone (3,4-DMMC), methylone and 3,4-methylenedioxypyrovalerone (MDPV), were assessed in the human kidney HK-2 cell line. All four derivatives elicited cell death in a concentration- and time-dependent manner, in the following order of potency: 3,4-DMMC >> MDPV > methylone ≈ pentedrone. 3,4-DMMC and methylone were selected to further elucidate the mechanisms behind synthetic cathinones-induced cell death. Both drugs elicited apoptotic cell death and prompted the formation of acidic vesicular organelles and autophagosomes in HK-2 cells. Moreover, the autophagy inhibitor 3-methyladenine significantly potentiated cell death, indicating that autophagy may serve as a cell survival mechanism that protects renal cells against synthetic cathinones toxicity. Both drugs triggered a rise in reactive oxygen and nitrogen species formation, which was completely prevented by antioxidant treatment with N­acetyl­L­cysteine or ascorbic acid. Importantly, these antioxidant agents significantly aggravated renal cell death induced by cathinone derivatives, most likely due to their autophagy-blocking properties. Taken together, our results support an intricate control of cell survival/death modulated by oxidative stress, apoptosis and autophagy in synthetic cathinones-induced renal injury.

Reliability of body-weight scalars on the assessment of propofol induction dose in obese patients.

BACKGROUND: Obese patients require specific perioperative care when compared with non-obese patients. The present study aimed to analyse the ability of size descriptors to estimate propofol induction dose in class II and III obese patients. METHODS: A cross-sectional study on adult patients with body mass index (BMI) equal to or greater than 35 kg/m2 and on adult patients with BMI lower than 35 kg/m2 was carried out. General anaesthesia was induced with remifentanil, propofol and rocuronium. Propofol infusion was started at 2000 mg/h until loss of consciousness. Bioelectrical impedance analysis and Brice modified interview was completed during pre- and post-operative evaluation, respectively. Measurements of propofol plasma concentration were performed using gas chromatography/ion trap-mass spectrometry. RESULTS: Forty patients were enrolled in the study. The median values of fat free mass (FFM) in BMI < 35 kg/m2 and BMI ≥ 35 kg/m2 groups were 70% and 55% of total body weight, respectively. Our results did not demonstrate a strong correlation level between the studied size descriptors and propofol induction dose in both groups. Nevertheless, when propofol doses were normalized by FFM, an apparent convergence of the empirical cumulative distribution functions was observed. CONCLUSION: None of the size descriptors was seen to be an effective predictor of the propofol induction dose in class II and III obese patients when a fixed infusion rate was used. Due to the observed variability between patients, guiding propofol induction dose against a clinical endpoint of unconsciousness appears more appropriate in order to avoid side effects related both with under or overdosing of propofol.

Genetic diversity and relatedness between Canindé and British Alpine goat breeds in Northeastern Brazil accessed by microsatellite markers.

The aim of this study was to access the genetic diversity and relatedness between Canindé and British Alpine goat breeds in the States of Piauí and Ceará using microsatellite markers. Genomic DNA was isolated from hair samples of 99 goats belonging to six different flocks. A panel of polymorphic heterologous microsatellite loci was used to genotype individuals. The microsatellite markers resulted in a total number of 145 alleles, with an average of 8.5 alleles per locus. The observed and expected heterozygosities were ≥0.687 and ≥0.627, respectively, for all loci. The polymorphic information content showed that all loci were highly informative with an overall mean of 0.757. Overall FST across all populations and loci was 18%, which was consistent with the coefficient of gene differentiation (GST = 0.104). AMOVA revealed that 12.8% of the variation was captured between breeds. The Bayesian STRUCTURE clustering detected the maximum likelihood for a model of two genetically distinct groups, in agreement with the number of predefined studied breeds and the two-dimensional plot from the PCoA analysis. The exotic British Alpine breed and the naturalized Brazilian Canindé breed were clearly differentiated by the microsatellite markers, indicating that these two breeds have distant genetic identities, despite the phenotypic similarity.

Adsorption-desorption reactions of selenium (VI) in tropical cultivated and uncultivated soils under Cerrado biome.

Soil management may affect selenium (Se) adsorption capacity. This study investigated adsorption and desorption of Se (VI) in selected Brazilian soils from the Cerrado biome, an area of ever increasing importance for agriculture expansion in Brazil. Soil samples were collected from cultivated and uncultivated soils, comprising clayed and sandy soils. Following chemical and mineralogical characterization, soil samples were subjected to Se adsorption and desorption tests. Adsorption was evaluated after a 72-h reaction with increasing concentrations of Se (0-2000 µg L-1) added as Na2SeO4 in a NaCl electrolyte solution (pH 5.5; ionic strength 15 mmol L-1). Desorption, as well as distribution coefficients (Kd) for selenate were also assessed. Soil management affected Se adsorption capacity, i.e., Se adsorbed amounts were higher for uncultivated soils, when compared to cultivated ones. Such results were also supported by data of Kd and maximum adsorption capacity of Se. This fact was attributed mainly to the presence of greater amounts of competing anions, especially phosphate, in cultivated soils, due to fertilizer application. Phosphate may compete with selenate for adsorption sites, decreasing Se retention. For the same group of soils (cultivated and uncultivated), Se adsorption was greater in the clayed soils compared to sandy ones. Our results support the idea that adding Se (VI) to the soil is a good strategy to increase Se levels in food crops (agronomic biofortification), especially when crops are grown in soils that have been cultivated over the time due to their low Se adsorption capacity (high Se availability).

Severe Supratentorial Intracerebral Hemorrhage: Factors Related to Brain Death Development.

OBJECTIVE: This study sought to identify clinical variables that may contribute to the development of brain death (BD) in patients with severe supratentorial intracerebral hemorrhage (ICH). METHODS: A prospective observational study was carried out from 2012 to 2014 and included patients with severe supratentorial ICH (Glasgow Coma Score ≤ 8). Exclusion criteria included aneurysmal or traumatic hemorrhage origin and hemorrhagic transformation of previous ischemic stroke. The following data were collected: clinical variables (past medical history, clinical severity at admission), head computed tomography scan findings, laboratory data, neurosurgical procedures, and immediate complications. Univariate tests and logistic regression analyses were performed to assess the predictive ability of these variables and identify patients at high risk of progression to BD. RESULTS: A total of 140 patients with severe supratentorial ICH (median age, 60; 68.6% male) were included. Of these 140 cases, 24 progressed to BD. In the multivariate analysis, the following variables were independently associated with BD outcome after supratentorial ICH: a history of arterial hypertension (odds ratio [OR], 11.254; P = .003), anticoagulant therapy (OR, 3.561; P = .050), presence of photomotor impairment at admission (OR, 7.095; P = .001), rebleeding after supratentorial ICH (OR, 5.613; P = .010), and no neurosurgical hematoma evacuation in ICH (OR, 8.314; P = .001). CONCLUSIONS: Certain clinical variables are predictive of an increased risk for BD development after supratentorial ICH. This information would be useful for transplant coordinators, permitting early identification of at-risk patients and increasing the availability of potential donors.

Genetic structure of goat breeds from Brazil and the United States: Implications for conservation and breeding programs.

The objective of this study was to assess genetic diversity among 5 Brazilian (155 animals) and 5 U.S. goat (120 animals) breeds using 23 microsatellite markers. Samples from the United States represented a broad geographic distribution whereas Brazilian samples were from the northeast region. Samples from Boer were common to each country's breed count. Expected and observed heterozygosity among breeds ranged from 0.55 to 0.72, suggesting ample genetic diversity in the breeds evaluated. United States Angora, U.S. Spanish, and Brazilian Nambi ranked highest for allelic richness, averaging 6.1, 7.1, and 6.5 alleles per locus, respectively. Angora and Spanish also ranked highest in private alleles (7 and 9, respectively). Using STRUCTURE, the U.S. Spanish were also found to share a common cluster assignment with Brazilian Nambi, suggesting that progenitor breeds may have been the same and passed through the Canary Islands or Cape Verde in route to the New World. When non-Boer breeds were pooled by country, the effect of the subpopulation compared with total population () = 0.05, suggesting minor genetic differences exist between countries. The lack of genetic structure among goat breeds when compared with other species (e.g., vs. ) suggests goat breeds may exhibit a plasticity that facilitates productivity across a wide range of countries and environments. Taken a step further, the concept of breed for meat goats may not be as relevant for goat production.

Deceased-donor Kidney Transplantation: Predictive Factors and Impact on Postoperative Outcome.

Kidney transplantation (KT) is the treatment of choice in end stage renal disease. Patients proposed for KT have multiple comorbidities, which makes KT a challenge. Our aim was to assess predictive factors for postoperative complications in deceased-donor KT. For data statistical analysis, logistic and linear regressions were used. Between 2012 and 2013, 113 KTs were performed in patients with a mean age 49.9 years. The most prevalent etiology was unknown (32.7%). All patients were in kidney replacement therapy (KRT), for an average of 5.7 years. Most had comorbidities before KT (84.1%), the most frequent hypertension (82.3%). Mean ischemia time (IT) was 1056 minutes. Complications occurred in 93.8% of cases. There were reinterventions in 12.4% of cases, and reinterventions in 13.3%. The time in KRT, IT, and ischemic heart disease had predictive power for the length of hospital stay. Diabetes mellitus before KT and IT were predictors for nephrourologic complications; anemia before KT for hematologic complications; and anemia before KT and time in KRT for cardiovascular complications. The morbidity associated with this disease points to the need to identify and improve the patient-dependent variables influencing its outcome, so as to improve short-term success.

Living-donor Kidney Transplantation: Predictive Factors and Impact on Post-transplant Outcome.

Renal transplantation from living donors represents a valuable opportunity for patients with end-stage renal disease due to short- and long-term outcomes. Nevertheless, it requires that a detailed set of conditions be considered for donor and recipient selection, with possible implications arising from these criteria in the post-transplant outcome. The present work aims to study demographic and clinical characteristics of donors and kidney recipients that predict post-transplantation outcomes after living donor kidney transplantation. With this aim, all patients who underwent donor nephrectomy and living donor transplantation between January 2012 and December 2013 were selected. Demographics, medical comorbidities, and postoperative outcomes were transcribed from electronic patient records. Linear and logistic regressions were applied for data analysis. The study sample consists of 40 patients who underwent living donor kidney transplantation. The presence of peripheral arterial disease and the etiology of end-stage renal disease were the only pretransplant variables that seem to independently predict hospitalization time. Simultaneously, the occurrence of urorenal and infectious complications had a statistically significant correlation with hospitalization time. Additionally, the incidence of cardiovascular complications was correlated with surgical reinterventions at a significant level. The results suggest that careful selection of the donor and the kidney recipient appears to be a prerequisite for a successful transplantation in vivo.

Living-donor and Deceased-donor Renal Transplantation: Differences in Early Outcome--A Single-center Experience.

Living-donor renal transplant (LDRT) yields better long-term outcomes than cadaver-donor renal transplant (CDRT). The aim of the present study was to identify the differences in the early postoperative period between LDRT and CDRT recipients. A retrospective study was conducted including all patients receiving a LDRT and CDRT in this center in 2012 and 2013. A total of 153 recipients were identified (CDRT n = 113, LDRT n = 40). On average, LDRT recipients were younger by 12.7 years (P < .001) and had fewer comorbidities (P < .05). There were no differences in gender or primary kidney disease. Mean time on dialysis, dialytic technique, and ischemia time were different between groups (P < .001, P < .01, P < .001, respectively). On average the length of hospital stay for LDRT recipients was 7 days shorter (P < .001). We found significant differences in the occurrence of early complications (P < .001) and its subtypes, with the exception of neurologic and respiratory complications. There were no differences in reinterventions and readmissions between groups. Recipients' age was an independent risk factor for overall postoperative complications and infectious complications; hypertension before renal transplant and cold ischemia time were predictors for cardiovascular complications; and cold ischemia time also was a predictor of nephrourologic and endocrine complications. CDRT patients had more postoperative complications during hospital stay. The variables identified as predictors of early outcome were different for the 2 groups of patients. Modifiable risk factors for better early outcomes and the impact of immediate complications in long-term graft survival must be investigated.

Predictors of mortality and poor functional outcome in severe spontaneous intracerebral hemorrhage: a prospective observational study.

OBJECTIVE: To analyze mortality and functional outcome in patients with severe spontaneous intracerebral hemorrhage (ICH), and identify the clinical characteristics, radiological findings and therapeutic procedures predictive of mortality in the Intensive Care Unit (ICU) and during hospitalization, as well as of poor functional results at 6 months. DESIGN: A prospective, observational study was carried out. SETTING: Neurocritical Care Unit of a university hospital. PATIENTS: Patients diagnosed with ICH were included over a period of 23 months. VARIABLES OF INTEREST: Demographic characteristics, cardiovascular risk factors, regular medication, laboratory test parameters, cranial CT findings, therapeutic procedures and outcome data. INTERVENTION: None. RESULTS: A total of 186 patients with ICH met the inclusion criteria. Surgery to evacuate ICH was performed in 25.8% of the patients. The mortality rate was 46.7%. The modified Rankin score at 6 months was 5 (RI: 4.6). Multivariate Cox regression analysis showed the presence of diabetes, prior anticoagulation, as well as APACHE II severity and the type of bleeding on the cranial CT scan to be predictors of mortality and poor functional outcomes. On the other hand, neurosurgical procedures and intracranial pressure (ICP) monitoring were associated with better outcomes. CONCLUSION: The presence of comorbidities such as diabetes, or previous anticoagulation, as well as the CT findings were associated to poorer outcomes. In contrast, ICP monitoring and early neurosurgery were predictive of longer survival and better functional outcomes.

Ultrastructure and morphogenesis of the wing scales in Heliconius erato phyllis (Lepidoptera: Nymphalidae): what silvery/brownish surfaces can tell us about the development of color patterning?

Usually the literature on Heliconius show three types of scales, classified based on the correlation between color and ultrastructure: type I - white and yellow, type II - black, and type III - orange and red. The ultrastructure of the scales located at the silvery/brownish surfaces of males/females is for the first time described in this paper. Besides, we describe the ontogeny of pigmentation, the scale morphogenesis and the maturation timing of scales fated to different colors in Heliconius erato phyllis. The silvery/brownish surfaces showed ultrastructurally similar scales to the type I, II and III. The ontogeny of pigmentation follows the sequence red, black, silvery/brownish and yellow. The maturation of yellow-fated scales, however, occurred simultaneously with the red-fated scales, before the pigmentation becomes visible. In spite of the scales at the silvery/brownish surfaces being ultrastructurally similar to the yellow, red and black scales, they mature after them; this suggests that the maturation timing does not show a relationship with the scale ultrastructure, with the deposition timing of the yellow pigment. The analysis of H. erato phyllis scale morphogenesis, as well as the scales ultrastructure and maturation timing, provided new findings into the developmental architecture of color pattern in Heliconius.

Sexual Size Dimorphism in the Color Pattern Elements of Two Mimetic Heliconius Butterflies.

Sexual dichromatism and sexual dimorphism of body size are reasonably well studied in butterflies. Sexual size dimorphism of color pattern elements, however, is much less explored. The object of this study is Heliconius, a genus of butterflies well known for the coevolution between mate color preferences and mimicry. Given the sexual role of wing coloration, we investigated the existence of sexual size dimorphism in the wing color elements of a mimetic pair-Heliconius erato phyllis Fabricius and Heliconius besckei Ménétriés-and analyzed the allometric patterns of these traits. Correlation between size of elements in the dorsal and ventral wing surfaces were also estimated. In both species, three out of four elements were larger in males, but the non-dimorphic element was not the same. With regard to the allometric patterns, our most important finding was that smaller males of one species have proportionally larger yellow bars. This is the first study specifically concerning quantitative sexual dimorphism in the coloration of this well-known genus of butterflies and it opens new prospects to investigate sex-related natural selection and sexual selection of color pattern elements.