Quality assurance of medicines supplied to low-income and middle-income countries: poor products in shiny boxes?

OBJECTIVE: In today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline 'Model Quality Assurance System (WHO MQAS) for procurement agencies', and we investigated factors favouring or hindering the adequate implementation of the guideline. METHODS: We used mixed-methods methodology to analyse quantitative and qualitative data. The quantitative study consisted of a retrospective secondary analysis of data collected by QUAMED (Quality Medicines for all), a partnership that pleads for universal access to quality-assured medicines. The qualitative survey consisted of formal and informal interviews with key informants. We adopted an embedded multiple-case study design. FINDINGS: Our analysis suggests that international distributors based in Europe perform, on average, better than sub-Saharan African distributors. However, some weaknesses are ubiquitous and concern critical processes, such as the initial selection of the products and the ongoing reassessment of their quality. This is due to several different factors: weak regulatory oversight, insufficient human/financial resources, weak negotiating power, limited judicial autonomy and/or lack of institutional commitment to quality. CONCLUSIONS: Our findings suggest that pharmaceutical distributors active in sub-Saharan Africa generally do not apply stringent criteria for selecting products and suppliers. Therefore, product quality is not consistently assured but depends on the requirements of purchasers. While long-term solutions are awaited, the WHO MQAS guideline should be used as an evaluation and training tool to upgrade current standards.

Hemocultivos en urgencias pediátricas. Guía práctica de recomendaciones: indicaciones, técnica de extracción, procesamiento e interpretación / Blood cultures in the paediatric emergency department. Guidelines and recommendations on their indications, collection, processing and interpretation

El hemocultivo (HC) es el método diagnóstico de elección ante la sospecha de bacteriemia, siendo una de las técnicas microbiológicas más solicitadas en pediatría. Diversos cambios han acontecido en los últimos años como la introducción de nuevas vacunas, el aumento creciente de pacientes portadores de catéteres vasculares centrales, o la irrupción de los sistemas automáticos de procesamiento de los HC. Dichos cambios han propiciado la revisión y la actualización de los distintos aspectos relacionados con esta técnica con el fin de optimizar su uso. Se presenta una guía práctica sobre recomendaciones acerca de la extracción, el procesamiento y la interpretación de los HC elaborada por la Sociedad Española de Urgencias de Pediatría y la Sociedad Española de Infectología Pediátrica. Tras revisar la información científica disponible, se presentan una serie de recomendaciones para cada uno de los siguientes apartados: indicaciones en Urgencias, técnica de extracción, transporte y procesamiento de la muestra, factores a tener en cuenta en situaciones especiales (indicaciones e interpretación de resultados en el paciente inmunodeprimido y/o portador de catéter vascular central, indicaciones de HC para anaerobios), diferenciación entre bacteriemia y contaminación ante un HC con crecimiento bacteriano y actitud a tomar ante un HC positivo en el paciente con fiebre sin foco

Blood culture (BC) is the gold standard when a bacteraemia is suspected, and is one of the most requested microbiological tests in paediatrics. Some changes have occurred in recent years: the introduction of new vaccines, the increasing number of patients with central vascular catheters, as well as the introduction of continuous monitoring BC systems. These changes have led to the review and update of different factors related to this technique in order to optimise its use. A practice guideline is presented with recommendations on BC, established by the Spanish Society of Paediatric Emergency Care and the Spanish Society for Paediatric Infectious Diseases. After reviewing the available scientific evidence, several recommendations for each of the following aspects are presented: BC indications in the Emergency Department, how to obtain, transport and process cultures, special situations (indications and interpretation of results in immunosuppressed patients and/or central vascular catheter carriers, indications for anaerobic BC), differentiation between bacteraemia and contamination when a BC shows bacterial growth and actions to take with a positive BC in patients with fever of unknown origin

[Blood cultures in the paediatric emergency department. Guidelines and recommendations on their indications, collection, processing and interpretation]. / Hemocultivos en urgencias pediátricas. Guía práctica de recomendaciones: indicaciones, técnica de extracción, procesamiento e interpretación.

Blood culture (BC) is the gold standard when a bacteraemia is suspected, and is one of the most requested microbiological tests in paediatrics. Some changes have occurred in recent years: the introduction of new vaccines, the increasing number of patients with central vascular catheters, as well as the introduction of continuous monitoring BC systems. These changes have led to the review and update of different factors related to this technique in order to optimise its use. A practice guideline is presented with recommendations on BC, established by the Spanish Society of Paediatric Emergency Care and the Spanish Society for Paediatric Infectious Diseases. After reviewing the available scientific evidence, several recommendations for each of the following aspects are presented: BC indications in the Emergency Department, how to obtain, transport and process cultures, special situations (indications and interpretation of results in immunosuppressed patients and/or central vascular catheter carriers, indications for anaerobic BC), differentiation between bacteraemia and contamination when a BC shows bacterial growth and actions to take with a positive BC in patients with fever of unknown origin.

Factores predictores de contaminación ante un hemocultivo con crecimiento bacteriano en Urgencias / Predictive factors of contamination in a blood culture with bacterial growth in an Emergency Department

Introducción: El objetivo del estudio es identificar factores predictores de contaminación ante un hemocultivo (HC) con crecimiento bacteriano realizado en un servicio de Urgencias. Pacientes y métodos Estudio prospectivo, observacional-analítico. Se incluyen los pacientes de uno a 36 meses, febriles, sin factores de riesgo para bacteriemia, con un HC realizado en el Servicio de Urgencias entre noviembre de 2011 y octubre de 2013 en el que se observa crecimiento bacteriano. Se analizan como posibles factores predictores de contaminación: temperatura máxima, tiempo de positividad, resultado inicial de la tinción de Gram, leucocitos totales, neutrófilos totales, neutrófilos inmaduros y proteína C reactiva (PCR). Resultados: Se incluyen 169 casos. El crecimiento bacteriano del HC se considera significativo (positivo) en 30 (17,8%), y contaminado en 139 (82,2%). Todos los factores predictores analizados, a excepción de la temperatura, presentan diferencias estadísticamente significativas entre los 2 grupos. Los 3 mejores predictores de contaminación son la PCR, el tiempo de positividad y el resultado inicial de la tinción de Gram. El valor predictivo positivo de una PCR≤30mg/L, un tiempo de positividad≥16h y una tinción de Gram con morfología bacteriana considerada como probable contaminación es del 95,1, 96,9 y 97,5%, respectivamente; el valor predictivo positivo es del 100% para la combinación de los 3 factores. Se reevalúan el 8,3% de los pacientes con un HC contaminado dados de alta inicialmente a domicilio. Conclusiones: La mayoría de HC con crecimiento bacteriano son finalmente considerados contaminados. El resultado inicial de la tinción de Gram, el tiempo de positividad y el valor de la PCR permiten identificarlos precozmente. Su pronta detección permitirá reducir las repercusiones negativas derivadas de los mismos (AU)

Introduction: The aim of this study is to identify predictive factors of bacterial contamination in positive blood cultures (BC) collected in an emergency department. Patients and methods: A prospective, observational and analytical study was conducted on febrile children aged on to 36 months, who had no risk factors of bacterial infection, and had a BC collected in the Emergency Department between November 2011 and October 2013 in which bacterial growth was detected. The potential BC contamination predicting factors analysed were: maximum temperature, time to positivity, initial Gram stain result, white blood cell count, absolute neutrophil count, band count, and C-reactive protein (CRP). Results: Bacteria grew in 169 BC. Thirty (17.8%) were finally considered true positives and 139 (82.2%) false positives. All potential BC contamination predicting factors analysed, except maximum temperature, showed significant differences between true positives and false positives. CRP value, time to positivity, and initial Gram stain result are the best predictors of false positives in BC. The positive predictive values of a CRP value≤30mg/L, BC time to positivity≥16h, and initial Gram stain suggestive of a contaminant in predicting a FP, are 95.1, 96.9 and 97.5%, respectively. When all 3 conditions are applied, their positive predictive value is 100%. Four (8.3%) patients with a false positive BC and discharged to home were revaluated in the Emergency Department. Conclusions: The majority of BC obtained in the Emergency Department that showed positive were finally considered false positives. Initial Gram stain, time to positivity, and CRP results are valuable diagnostic tests in distinguishing between true positives and false positives in BC. The early detection of false positives will allow minimising their negative consequences (AU)

[Predictive factors of contamination in a blood culture with bacterial growth in an Emergency Department]. / Factores predictores de contaminación ante un hemocultivo con crecimiento bacteriano en Urgencias.

INTRODUCTION: The aim of this study is to identify predictive factors of bacterial contamination in positive blood cultures (BC) collected in an emergency department. PATIENTS AND METHODS: A prospective, observational and analytical study was conducted on febrile children aged on to 36 months, who had no risk factors of bacterial infection, and had a BC collected in the Emergency Department between November 2011 and October 2013 in which bacterial growth was detected. The potential BC contamination predicting factors analysed were: maximum temperature, time to positivity, initial Gram stain result, white blood cell count, absolute neutrophil count, band count, and C-reactive protein (CRP). RESULTS: Bacteria grew in 169 BC. Thirty (17.8%) were finally considered true positives and 139 (82.2%) false positives. All potential BC contamination predicting factors analysed, except maximum temperature, showed significant differences between true positives and false positives. CRP value, time to positivity, and initial Gram stain result are the best predictors of false positives in BC. The positive predictive values of a CRP value≤30mg/L, BC time to positivity≥16h, and initial Gram stain suggestive of a contaminant in predicting a FP, are 95.1, 96.9 and 97.5%, respectively. When all 3 conditions are applied, their positive predictive value is 100%. Four (8.3%) patients with a false positive BC and discharged to home were revaluated in the Emergency Department. CONCLUSIONS: The majority of BC obtained in the Emergency Department that showed positive were finally considered false positives. Initial Gram stain, time to positivity, and CRP results are valuable diagnostic tests in distinguishing between true positives and false positives in BC. The early detection of false positives will allow minimising their negative consequences.

Early L-dopa, but not pramipexole, restores basal ganglia activity in partially 6-OHDA-lesioned rats.

The most appropriate time for the initiation of dopaminergic symptomatic therapy in Parkinson's disease remains debatable. It has been suggested that early correction of basal ganglia pathophysiological abnormalities may have long-term beneficial effects. To test this hypothesis, we investigated the early and delayed actions of L-dopa and pramipexole, using a delayed-start protocol of treatment. The effects of early and delayed administration of these drugs on motor response, development of dyskinesias, neurogenesis and molecular markers in basal ganglia were studied in rats with a unilateral and partial 6-hydroxydopamine-induced nigrostriatal lesion. Ten days after lesioning, rats received treatment with: a) L-dopa methyl ester (25mg/kg with 6.25mg/kg of benserazide, i.p., twice a day); b) pramipexole (0.5mg/kg, sc, twice a day) or c) saline for 4weeks. Four weeks after treatment initiation, rats from the saline group were distributed in three groups that then received the following treatments: d) L-dopa, e) pramipexole or f) saline, for 4weeks more. Three animals in each treatment arm received 5-bromo-2-deoxyuridine injections (200mg/kg) 3days before starting treatment. When compared with delayed-start L-dopa, early-start L-dopa treatment induced a lower rotational response (p<0.01), an improvement in limb akinesia (p<0.05), a lower level of dyskinesia (p<0.01) and a normalization of lesion-induced molecular changes in basal ganglia. When compared with delayed-start pramipexole, early-start pramipexole induced a higher rotational response (p<0.01), but did not improve limb akinesia, induce dyskinesia nor normalize lesion-induced molecular changes. Neither significant modifications of striatal dopamine D1-D3 receptor heteromerization nor subventricular zone neurogenesis was found after any L-dopa or pramipexole treatments. Our data support a possible restoration of basal ganglia physiological mechanisms by early-start L-dopa therapy.

Imbalance of p75(NTR)/TrkB protein expression in Huntington's disease: implication for neuroprotective therapies.

Neuroprotective therapies based on brain-derived neurotrophic factor (BDNF) administration have been proposed for Huntington's disease (HD) treatment. However, our group has recently reported reduced levels of TrkB in HD mouse models and HD human brain suggesting that besides a decrease on BDNF levels a reduction of TrkB expression could also contribute to diminished neurotrophic support in HD. BDNF can also bind to p75 neurotrophin receptor (p75(NTR)) modulating TrkB signaling. Therefore, in this study we have analyzed the levels of p75(NTR) in several HD models, as well as in HD human brain. Our data demonstrates a p75(NTR)/TrkB imbalance in the striatum of two different HD mouse models, Hdh(Q111/111) homozygous knockin mice and R6/1 mice that was also manifested in the putamen of HD patients. The imbalance between TrkB and p75(NTR) levels in a HD cellular model did not affect BDNF-mediated TrkB activation of prosurvival pathways but induced activation of apoptotic cascades as demonstrated by increased JNK phosphorylation. Moreover, BDNF failed to protect mutant huntingtin striatal cells transfected with p75(NTR) against NMDA-mediated excitotoxicity, which was associated with decreased Akt phosphorylation. Interestingly, lack of Akt activation following BDNF and NMDA treatment correlated with increased PP1 levels. Accordingly, pharmacological inhibition of PP1 by okadaic acid (OA) prevented mutant huntingtin striatal cell death induced by NMDA and BDNF. Altogether, our findings demonstrate that the p75(NTR)/TrkB imbalance induced by mutant huntingtin in striatal cells associated with the aberrant activity of PP1 disturbs BDNF neuroprotection likely contributing to increasing striatal vulnerability in HD. On the basis of this data we hypothesize that normalization of p75(NTR) and/or TrkB expression or their signaling will improve BDNF neuroprotective therapies in HD.

Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity.

Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disorder caused by an expanded CAG/polyglutamine repeat in the coding region of the huntingtin (htt) gene. Although HD is classically considered a motor disorder, there is now considerable evidence that early cognitive deficits appear in patients before the onset of motor disturbances. Here we demonstrate early impairment of long-term spatial and recognition memory in heterozygous HD knock-in mutant mice (Hdh(Q7/Q111)), a genetically accurate HD mouse model. Cognitive deficits are associated with reduced hippocampal expression of CREB-binding protein (CBP) and diminished levels of histone H3 acetylation. In agreement with reduced CBP, the expression of CREB/CBP target genes related to memory, such c-fos, Arc and Nr4a2, was significantly reduced in the hippocampus of Hdh(Q7/Q111) mice compared with wild-type mice. Finally, and consistent with a role of CBP in cognitive impairment in Hdh(Q7/Q111) mice, administration of the histone deacetylase inhibitor trichostatin A rescues recognition memory deficits and transcription of selective CREB/CBP target genes in Hdh(Q7/Q111) mice. These findings demonstrate an important role for CBP in cognitive dysfunction in HD and suggest the use of histone deacetylase inhibitors as a novel therapeutic strategy for the treatment of memory deficits in this disease.

Infección invasiva por «Staphylococcus aureus» resistente a meticilina de origen comunitario en pacientes pediátricos sanos / Invasive infection caused by community acquired methicillin resistant Staphylococcus aureus on healthy pediatric patients

Staphylococcus aureus resistente a meticilina de adquisición comunitaria (SARM-AC) es una bacteria implicada en infecciones de diversa gravedad y localización. En este trabajo exponemos la actualidad de las infecciones por SARM-AC en pediatría, y lo ilustramos con dos ejemplos de infección virulenta en pacientes pediátricos sanos. El primer caso corresponde a una paciente con artritis séptica y neumonía necrosante por SARM-AC, y el segundo a un lactante con pleuroneumonía por SARM-AC. Ambos casos son un claro ejemplo de la relevancia de esta infección emergente en pediatría (AU)

The community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) is a bacterium that is frequently involved in severe infections and various locations. In this article we describe the actual state of CA-MRSA infections in pediatrics, and we illustrate it with two examples of virulent infection in healthy pediatric patients. The first case is in a patient with septic arthritis and necrotizing pneumonia caused by CA-MRSA, and the second one is in an unweaned baby with pleuropneumonia caused by CA-MRSA. Both cases are a clear example of the importance of this emerging infection in pediatrics (AU)

BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington's disease.

Brain-derived neurotrophic factor (BDNF) is the main candidate for neuroprotective therapeutic strategies for Huntington's disease. However, the administration system and the control over the dosage are still important problems to be solved. Here we generated transgenic mice overexpressing BDNF under the promoter of the glial fibrillary acidic protein (GFAP) (pGFAP-BDNF mice). These mice are viable and have a normal phenotype. However, intrastriatal administration of quinolinate increased the number of reactive astrocytes and enhanced the release of BDNF in pGFAP-BDNF mice compared with wild-type mice. Coincidentally, pGFAP-BDNF mice are more resistant to quinolinate than wild-type mice, suggesting a protective effect of astrocyte-derived BDNF. To verify this, we next cultured astrocytes from pGFAP-BDNF and wild-type mice for grafting. Wild-type and pGFAP-BDNF-derived astrocytes behave similarly in nonlesioned mice. However, pGFAP-BDNF-derived astrocytes showed higher levels of BDNF and larger neuroprotective effects than the wild-type ones when quinolinate was injected 30 days after grafting. Interestingly, mice grafted with pGFAP-BDNF astrocytes showed important and sustained behavioral improvements over time after quinolinate administration as compared with mice grafted with wild-type astrocytes. These findings show that astrocytes engineered to release BDNF can constitute a therapeutic approach for Huntington's disease.

PH domain leucine-rich repeat protein phosphatase 1 contributes to maintain the activation of the PI3K/Akt pro-survival pathway in Huntington's disease striatum.

Dysregulation of gene expression is one of the mechanisms involved in the pathophysiology of Huntington's disease (HD). Here, we examined whether mutant huntingtin regulates the levels of PH domain leucine-rich repeat protein phosphatase 1 (PHLPP1), a phosphatase that specifically dephosphorylates Akt at Ser473. Our results show decreased PHLPP1 protein levels in knock-in models (Hdh(Q111/Q111) mouse striatum and STHdh(Q111/Q111) cells), in the striatum of N-terminal exon-1 mutant huntingtin transgenic mouse models (R6/1; R6/1 : BDNF + or - , R6/2 and Tet/HD94) and in the putamen of HD patients. Quantitative PCR analysis revealed a reduction in PHLPP1 mRNA levels in the striatum of R6/1 compared with wild-type mice. Coincident with reduced PHLPP1 protein levels, we observed increased phosphorylated Akt (Ser473) levels specifically in the striatum. The analysis of the conditional mouse model Tet/HD94 disclosed that after mutant huntingtin shutdown PHLPP1 levels returned to wild-type levels whereas phospho-Akt levels were partially reduced. In conclusion, our results show that mutant huntingtin downregulates PHLPP1 expression. In the striatum, these reduced levels of PHLPP1 can contribute to maintain high levels of activated Akt that may delay cell death and allow the recovery of neuronal viability after mutant huntingtin silencing.

Evaluación del grado de satisfacción con la dispensación en una unidad de pacientes externos en una farmacia de hospital / Evaluation of the degree of satisfaction with the dispense in an outpatient unit in a hospital pharmacy

Objetivo: Valorar y cuantificar el grado de satisfacción de los pacientes respecto al trato y la información que reciben en la unidad de pacientes externos de un hospital. Método: Estudio descriptivo de corte transversal, desarrollado durante 2 meses en pacientes ambulatorios mayores de 18 años que han querido participar. Para registrar el grado de satisfacción de los pacientes se ha utilizado un cuestionario autoadministrado, semiestructurado y validado. Resultados: En total se ha entrevistado a 81 pacientes, 46 hombres y 35 mujeres. Un 91,1% de los pacientes valora positivamente el interés que mostró el personal durante la dispensación. Un 82,2% afirma haber recibido la información adecuada de los medicamentos. Un 67,1% indica haber aprendido a conocerlos medicamentos. Un 72% de los pacientes afirma haber recibido la información necesaria como para valorar importante la adherencia a los fármacos, aunque sólo un 55% indica conocer sus efectos secundarios. La satisfacción con el servicio de farmacia en general resulta ser de un 97,3%. Conclusiones: El grado de satisfacción y de confianza de los pacientes ambulatorios con el servicio de farmacia es alto, ya que la mayoría se muestran satisfechos con el trato recibido y aprecian la diligencia de los profesionales implicados; sin embargo, es necesario mejorar el proceso de educación sanitaria, ya que casi un 30% no está satisfecho con la información recibida sobre los efectos adversos potenciales (AU)

Objective: To assess and quantify the patients' degree of satisfaction relative to the treatment and information they receive in a hospital outpatient unit. Method: Descriptive, cross-sectional study, developed during two months in outpatients over 18 years old, who wanted to participate.In order to record the patients' degree of satisfaction, a self-administered, semi-structured and validated questionnaire has been administered. Results: A total of 81 patients were interviewed, being 46 male and 35 female. 91.1% of the patients have a positive assessment of the interest shown by the staff during dispense. 82.2% state to have received the suitable information about the medications. 67.1% confirmed they learned to know their medications. 72% of the patients state to have received the necessary information to assess the importance of adhesion to the medicines, although just 55% confirms knowing the medicine adverse effects. The result of satisfaction with the pharmacy in general is 97.3%. Conclusions: The outpatients' degree of satisfaction and confidence with the pharmacist service is high, since most of the mare satisfied with the treatment received and appreciate the diligence of the professionals involved; however, it is necessary to improve the health education process as nearly 30% are not satisfied with the information received about the potential adverse effects (AU)

Brain-derived neurotrophic factor modulates the severity of cognitive alterations induced by mutant huntingtin: involvement of phospholipaseCgamma activity and glutamate receptor expression.

The involvement of brain-derived neurotrophic factor (BDNF) in cognitive processes and the decrease in its expression in Huntington's disease suggest that this neurotrophin may play a role in learning impairment during the disease progression. We therefore analyzed the onset and severity of cognitive deficits in two different mouse models with the same mutant huntingtin but with different levels of BDNF (R6/1 and R6/1:BDNF+/- mice). We observed that BDNF modulates cognitive function in different learning tasks, even before the onset of motor symptoms. R6/1:BDNF+/- mice showed earlier and more accentuated cognitive impairment than R6/1 mice at 5 weeks of age in discrimination learning; at 5 weeks of age in procedural learning; and at 9 weeks of age in alternation learning. At the earliest age at which cognitive impairment was detected, electrophysiological analysis was performed in the hippocampus. All mutant genotypes showed reduced hippocampal long term potentiation (LTP) with respect to wild type but did not show differences between them. Thus, we evaluated the involvement of BDNF-trkB signaling and glutamate receptor expression in the hippocampus of these mice. We observed a decrease in phospholipaseCgamma activity, but not ERK, in R61, BDNF+/- and R6/1:BDNF+/- hippocampus at the age when LTP was altered. However, a specific decrease in the expression of glutamate receptors NR1, NR2A and GluR1 was detected only in R6/1:BDNF+/- hippocampus. Therefore, these results show that BDNF modulates the learning and memory alterations induced by mutant huntingtin. This interaction leads to intracellular changes, such as specific changes in glutamate receptors and in BDNF-trkB signaling through phospholipaseCgamma.

Fiebre en el lactante menor de 3 meses: incidencia de enfermedad bacteriana potencialmente grave y utilidad de los test de diagnóstico rápido virológico / Fever in infants aged less than three months: incidence of potentially serious bacterial disease and usefulness of the rapid virological diagnostic tests

Objetivos: Determinar la incidencia y la etiología de la enfermedad bacteriana potencialmente grave (EBPG), de la infección vírica y de la coinfección (vírica y bacteriana) en una muestra de lactantes febriles menores de tres meses. Métodos: Estudio prospectivo de lactantes menores de tres meses que ingresaron en nuestro centro por fiebre. A todos ellos se les realizó estudio completo de sepsis, con punción lumbar en casos seleccionados. Se define enfermedad bacteriana potencialmente grave como el crecimiento de un microorganismo bacteriano en sangre, orina o líquido cefalorraquídeo. Se determinó la presencia de virus respiratorio sincitial (VRS) y virus Influenzae A y B durante el período epidémico, y la presencia de enterovirus, por reacción en cadena de la polimerasa, en 11 pacientes menores de un mes. Para el análisis de los resultados se utilizó el programa SPSS (versión 12.0). Resultados: Se incluyeron 136 lactantes febriles menores de tres meses. Cumplían los criterios de bajo riesgo de Rochester 70 pacientes (51,5%). Los diagnósticos finales más frecuentes fueron síndrome febril sin foco e infección urinaria. En 33 casos (24,3%) se demostró una EBPG (31 urocultivos, 2 cultivos de líquido cefalorraquídeo y 7 hemocultivos resultaron positivos). La incidencia de infección vírica demostrada fue del 30,8%. En 2 pacientes se demostró coinfección vírica y bacteriana (un 4,8% del total de los pacientes infectados por virus). Se detectó la presencia de enterovirus en líquido cefalorraquídeo en 5 (45,5%) de 11 casos estudiados, ninguno de ellos mostró cultivos bacterianos positivos. Discusión: En nuestro estudio, la infección urinaria se muestra como la enfermedad bacteriana potencialmente grave con mayor incidencia, superior a la hallada en otras series. La incorporación a los algoritmos diagnósticos de los test de diagnóstico rápido virológico ayuda a seleccionar a los lactantes con menor riesgo de padecer enfermedad bacteriana, y abre nuevas perspectivas en el manejo del lactante febril menor de tres meses (AU)

Aims: To assess the incidence and aetiology of potentially serious bacterial disease (PSBD), viral infection and viral-bacterial coinfection in a sample of febrile infants aged less than three months. Methods: Prospective study of infants aged less than three months admitted to our hospital because of fever. A complete sepsis study was performed in all cases, with lumbar tap in selected cases. PSBD is defined as the growth of bacteria in blood, urine or cebrospinal fluid (CSF). The presence of Respiratory Syncitial Virus and of influenza A and B viruses was assessed during the epidemic period, and enteroviruses were investigated using the polymerase chain reaction in eleven patients aged less than one month. The SPSS 12.0 software was used for the analysis. Results: The study population comprised 136 infants aged less than three months. Seventy patients (51.5%) met the Rochester low-risk criteria. The most common final diagnoses were non-focal febrile syndrome and urinary infection. PSBD was demonstrated in 33 cases (24.3%) (31 urine cultures, 2 CSF cultures and 7 blood cultures were positive). The incidence of documented viral infection was 30.8%. Viral and bacterial coinfection was demonstrated in 2 cases (4.8% of the total number of virus-infected patients). Enterovirus was demonstrated in the CSF in 5 (45.5%) of 11 cases studied; none of them had positive bacterial cultures. Discussion: In the present study, urinary infection was the most frequently occurring potentially serious bacterial disease, with an incidence higher than those reported in other series. The inclusion of rapid virological diagnostic tests in the diagnostic algorithms helps in selecting those infants with lower risk of bacterial infection and opens new perspectives for the management of febrile infants aged less than three months (AU)

[SPECT-CT 67Ga studies in lymphoma disease. Contribution to staging and follow-up]. / Estudios SPECT-TAC con Ga de la enfermedad linfomatosa. Su aportación en la estadificación y seguimiento de la enfermedad.

INTRODUCTION: 67Ga scintigraphy is an established method for the staging and follow-up of patients diagnosed of lymphomas. The aim of this study is to evaluate advantages of 67Ga SPECT-CT study over planar, SPECT and high resolution CT studies in lymphoma disease. MATERIAL AND METHODS: One hundred and one 67Ga studies corresponding to 74 patients (46 men) were obtained, mean age 44 years. Thirty-eight patients (51 %) were diagnosed of Hodgkin's lymphoma and 36 were non-Hodgkin's lymphoma. All patients were evaluated with 67Ga and high-resolution CT studies. 67Ga studies were performed in a hybrid system, obtaining planar, SPECT and fused SPECT-CT imaging. Findings obtained from 67Ga studies were correlated with findings obtained from CT studies, both much in number of tumoral lesions and in their localization. RESULTS: Planar, SPECT, SPECT-CT and CT studies detected 123, 146, 155 and 132 lesions respectively. SPECT-CT and CT were concordant in 52 studies, while there was no concordance between SPECT-CT and CT in the remaining 49 studies, SPECT-CT detecting more lesions than CT in 28 of them. These findings changed the disease stage 18 times (18 % of whole studies). CONCLUSION: These results show better efficiency of 67Ga SPECT-CT compared to the other acquisition methods of 67Ga study and to CT for detection of tumoral lymphomatous lesions. 67Ga SPECT-CT study improves the diagnostic yield of the study with 67Ga in patients with lymphoma, providing better anatomical localization of tumoral lesions and detection of extraganglionar disease.

Estudios SPECT-TAC con 67Ga de la enfermedad linfomatosa. Su aportación en la estadificación y seguimiento de la enfermedad / SPECT-CT 67Ga studies in lymphoma disease. Contribution to staging and follow-up

Introducción. La gammagrafía con 67Ga es un método establecido en la estadificación y seguimiento de los pacientes diagnosticados de linfoma. El objetivo de este estudio es valorar las ventajas de la gammagrafía con 67Ga y SPECT-TAC sobre los estudios planares y SPECT y sobre la TAC de alta resolución en la enfermedad linfomatosa. Material y métodos. Se analizaron 101 estudios con 67Ga pertenecientes a 74 pacientes (46 hombres), edad media 44 años. Treinta y ocho pacientes (51 %) estaban diagnosticados de linfoma de Hodgkin y 36 no hodgkinianos. Todos los pacientes fueron evaluados mediante estudio con 67Ga y TAC de alta resolución. La exploración con 67Ga se realizó en un sistema híbrido, obteniendo imágenes planares, SPECT y fusión SPECT-TAC. Los resultados obtenidos de los estudios con 67Ga se compararon con los de la TAC, tanto en número de lesiones como en su localización. Resultados. Los estudios planares, SPECT, SPECT-TAC y TAC detectaron 123, 146, 155 y 132 lesiones, respectivamente. La SPECT-TAC y la TAC fueron coincidentes en 52 estudios, mientras que en los otros 49 estudios no hubo concordancia en número de lesiones, detectando la SPECT-TAC más lesiones que la TAC en 28 de ellos, modificando la estadificación de la enfermedad en 18 ocasiones (18 % de los estudios). Conclusiones. Estos resultados muestran una mayor efectividad del estudio de 67Ga y fusión SPECT-TAC en comparación con los otros métodos de adquisición gammagráficos y con la TAC de alta resolución en la detección de lesiones linfomatosas. Este método mejora el rendimiento diagnóstico de los estudios con 67Ga, aportando una mejor localización anatómica de las lesiones y permitiendo detectar lesiones extraganglionares

Introduction. 67Ga scintigraphy is an established method for the staging and follow-up of patients diagnosed of lymphomas. The aim of this study is to evaluate advantages of 67Ga SPECT-CT study over planar, SPECT and high resolution CT studies in lymphoma disease. Material and methods. One hundred and one 67Ga studies corresponding to 74 patients (46 men) were obtained, mean age 44 years. Thirty-eight patients (51 %) were diagnosed of Hodgkin's lymphoma and 36 were non-Hodgkin's lymphoma. All patients were evaluated with 67Ga and high-resolution CT studies. 67Ga studies were performed in a hybrid system, obtaining planar, SPECT and fused SPECT-CT imaging. Findings obtained from 67Ga studies were correlated with findings obtained from CT studies, both much in number of tumoral lesions and in their localization. Results. Planar, SPECT, SPECT-CT and CT studies detected 123, 146, 155 and 132 lesions respectively. SPECT-CT and CT were concordant in 52 studies, while there was no concordance between SPECT-CT and CT in the remaining 49 studies, SPECT-CT detecting more lesions than CT in 28 of them. These findings changed the disease stage 18 times (18 % of whole studies). Conclusion. These results show better efficiency of 67Ga SPECT-CT compared to the other acquisition methods of 67Ga study and to CT for detection of tumoral lymphomatous lesions. 67Ga SPECT-CT study improves the diagnostic yield of the study with 67Ga in patients with lymphoma, providing better anatomical localization of tumoral lesions and detection of extraganglionar disease

[123I-MIBG SPECT-CT combined with gamma probe for radioguided localization of pheochromocytoma]. / SPECT-TC con 123I-MIBG y sonda gamma portátil en la localización radioguiada de un feocromocitoma.

We report a case of a 56-year-old male with high suspicion of an intraabdominal catecholamine-producer tumor. The patient underwent different diagnostic procedures including 123I-meta-iodobenzylguanidine (123I-MIBG) scintigraphy, with subsequent SPECT and low resolution CT for attenuation correction and anatomic and functional image fusion. After practicing a new 123I-MIBG scintigraphy the patient was taken to the operating room, where a hand-held gamma probe detector helped to localize the lesion.

SPECT-TC con 123I-MIBG y sonda gamma portátil en la localización radioguiada de un feocromocitoma / 123I-MIBG SPECT-CT combined with gamma probe for radioguided localization of pheochromocytoma

Presentamos el caso de un hombre de 56 años con elevada sospecha de tumoración intraabdominal productora de catecolaminas. El paciente fue sometido a diversas pruebas diagnósticas, entre las que se incluyó un rastreo gammagráfico con 123I-metayodobencilguanidina (123I-MIBG), complementado con SPECT y TC de baja resolución para corrección de atenuación y posterior fusión de las imágenes anatómicas y funcionales. Después de un nuevo rastreo con 123I-MIBG el paciente fue intervenido quirúrgicamente con el apoyo intraoperatorio de una sonda gamma portátil, que facilitó la localización de la tumoración

We report a case of a 56-year-old male with high suspicion of an intraabdominal catecholamine-producer tumor. The patient underwent different diagnostic procedures including 123I-meta-iodobenzylguanidine (123I-MIBG) scintigraphy, with subsequent SPECT and low resolution CT for attenuation correction and anatomic and functional image fusion. After practicing a new 123I-MIBG scintigraphy the patient was taken to the operating room, where a hand-held gamma probe detector helped to localize the lesion