Transition of Adolescents With Severe Asthma From Pediatric to Adult Care in Spain: The STAR Consensus.

OBJECTIVES: To assess the degree of consensus among a multidisciplinary expert panel on the transition of adolescents with severe asthma from pediatric to adult care. METHODS: A 61-item survey was developed based on guidelines for other chronic diseases, covering transition planning, preparation, effective transfer, and follow-up. A 2-round Delphi process assessed the degree of consensus among 98 experts (49 pediatricians, 24 allergists, and 25 pulmonologists). Consensus was established with ≥70% agreement. RESULTS: Consensus was reached for 42 items (70%). Panelists were unable to agree on an age range for initiation of transition. The main goal during the transition identified by the experts is for adolescents to gain autonomy in managing severe asthma and prescribed treatments. The panelists agreed on the importance of developing an individualized plan, promoting patient autonomy, and identifying factors associated with the home environment. They agreed that the adult health care team should have expertise in severe asthma, biologics, and management of adolescent patients. Pediatric and adult health care teams should share clinical information, agree on the criteria for maintaining biological therapy, and have an on-site joint visit with the patient before the effective transfer. Adult health care professionals should closely follow the patient after the effective transfer to ensure correct inhaler technique, adherence, and attendance at health care appointments. CONCLUSION: This consensus document provides the first roadmap for Spanish pediatric and adult teams to ensure that key aspects of the transition process in severe asthma are covered. The implementation of these recommendations will improve the quality of care offered to the patient.

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine.

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4'-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4'-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4'-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.

Etiología y patrones de resistencia antimicrobiana en sepsis neonatal temprana y tardía, en una Unidad de Terapia Intensiva Neonatal / Etiology and antimicrobial resistance patterns in early and late neonatal sepsis in a Neonatal Intensive Care Unit

Introducción. La sepsis neonatal es una de las principales causas de muerte en recién nacidos. El tratamiento antimicrobiano empírico se sustenta en información epidemiológica y pruebas de susceptibilidad antimicrobiana. El objetivo del estudio fue describir los agentes etiológicos y su sensibilidad antimicrobiana enreciénnacidos con sepsis temprana (SNTe) o tardía (SNTa) de una Unidad de Terapia Intensiva Neonatal. Métodos. Estudio transversal realizado en un hospital de concentración del occidente de México. Se determinó la resistencia antimicrobiana de los gérmenes aislados en sangre o líquido cefalorraquídeo de pacientes con SNTe o SNTa nosocomial. Resultados. Se aislaron bacterias o levaduras en 235 cultivos de 67 eventos de SNTe y 166 eventos de SNTa. Del total de aislamientos, las bacterias más frecuentes fueron enterobacterias (51,5%), seguidas de Streptococcus spp. en SNTe y Staphylococcus spp. en SNTa. En cuanto a las enterobacterias de adquisición nosocomial, el 40% fueron productoras de betalactamasas de espectro extendido. En especies de Staphylococcus, la resistencia a oxacilina se registró en el 65,5%. En las enterobacterias (n: 121), la frecuencia de resistencia a amikacina, piperacilina-tazobactam y meropenem fue menor del 3%. En bacterias no fermentadoras, no se observó resistencia a amikacina, ciprofloxacino y cefepime; sin embargo, el número de aislamientos fue escaso. Conclusiones. Las bacterias identificadas con mayor frecuencia en SNTe fueron enterobacterias (67,6%) y Streptococcus spp. (17,6%), mientras que, en SNTa, fueron enterobacterias (44,9%) y Staphylococcus spp. (34,7%). El 40% de las enterobacterias de adquisición nosocomial fueron productoras de betalactamasas de espectro extendido y el 65,5% de Staphylococcus spp. mostraron resistencia a oxacilina.

Introduction. Neonatal sepsis is one of the main causes of death among newborn infants. Empirical antimicrobial treatment is based on epidemiological information and antimicrobial susceptibility tests. The objective of this study was to describe etiologic agents and their antimicrobial susceptibility among newborn infants with early-onset neonatal sepsis (EONS) or late-onset neonatal sepsis (LONS) at a Neonatal Intensive Care Unit. Methods. Cross-sectional study conducted at a tertiary referral hospital in Western Mexico. Determination of antimicrobial resistance of microorganisms isolated in blood or cerebrospinal fluid of patients with EONS or nosocomial LONS. Results. Yeasts and bacteria were isolated from 235 cultures corresponding to 67 events of EONS and 166 events of LONS. Of all isolates, the most common bacteria were Enterobacteriaceae (51.5%), followed by Streptococcus spp. in EONS, and by Staphylococcus spp. in LONS. Of all nosocomial Enterobacteriaceae, 40% were extended spectrum beta-lactamase producing bacteria. Among Staphylococcus species, resistance to oxacillin was recorded in 65.5%. Among Enterobacteriaceae (n: 121), resistance to amikacin, piperacillin-tazobactam, and meropenem was below 3%. Non-fermenting bacteria did not show resistance to amikacin, ciprofloxacin or cefepime; however, the number of isolates was scarce. Conclusions.The most commonly identified bacteria in EONS were Enterobacteriaceae (67.6%) and Streptococcus spp. (17.6%), and Enterobacteriaceae (44.9%) and Staphylococcus spp. (34.7%) in LONS. Forty percent ofnosocomial Enterobacteriaceae were extended spectrum beta-lactamase producing bacteria, and 65.5% of Staphylococcus spp. showed resistance to oxacillin.

Etiology and antimicrobial resistance patterns in early and late neonatal sepsis in a Neonatal Intensive Care Unit.

INTRODUCTION: Neonatal sepsis is one of the main causes of death among newborn infants. Empirical antimicrobial treatment is based on epidemiological information and antimicrobial susceptibility tests. The objective of this study was to describe etiologic agents and their antimicrobial susceptibility among newborn infants with early-onset neonatal sepsis (EONS) or late-onset neonatal sepsis (LONS) at a Neonatal Intensive Care Unit. METHODS: Cross-sectional study conducted at a tertiary referral hospital in Western Mexico. Determination of antimicrobial resistance of microorganisms isolated in blood or cerebrospinal fluid of patients with EONS or nosocomial LONS. RESULTS: Yeasts and bacteria were isolated from 235 cultures corresponding to 67 events of EONS and 166 events of LONS. Of all isolates, the most common bacteria were Enterobacteriaceae (51.5%), followed by Streptococcus spp. in EONS, and by Staphylococcus spp. in LONS. Of all nosocomial Enterobacteriaceae, 40% were extended spectrum beta-lactamase producing bacteria. Among Staphylococcus species, resistance to oxacillin was recorded in 65.5%. Among Enterobacteriaceae (n: 121), resistance to amikacin, piperacillin-tazobactam, and meropenem was below 3%. Non-fermenting bacteria did not show resistance to amikacin, ciprofloxacin or cefepime; however, the number of isolates was scarce. CONCLUSIONS: The most commonly identified bacteria in EONS were Enterobacteriaceae (67.6%) and Streptococcus spp. (17.6%), and Enterobacteriaceae (44.9%) and Staphylococcus spp. (34.7%) in LONS. Forty percent ofnosocomial Enterobacteriaceae were extended spectrum beta-lactamase producing bacteria, and 65.5% of Staphylococcus spp. showed resistance to oxacillin.

Archived HIV-1 DNA resistance mutations to rilpivirine and etravirine in successfully treated HIV-1-infected individuals pre-exposed to efavirenz or nevirapine.

OBJECTIVES: Efavirenz and nevirapine failure is associated with a rapid selection of resistance-associated mutations (RAMs), which may impact on etravirine or rilpivirine susceptibility. However, RAMs for rilpivirine and etravirine cannot be reported on previous resistance genotypes because these specific RAMs were not analyzed at that time. Therefore, our objective was to determine, in virologically suppressed HIV-1-infected individuals, the presence of RAMs to rilpivirine, etravirine and the combination of tenofovir/emtricitabine/rilpivirine in HIV-1 DNA from individuals previously exposed to efavirenz and/or nevirapine. METHODS: The studied population included 169 treatment-experienced individuals enrolled in the ANRS 138-EASIER trial who previously failed on and/or were intolerant to efavirenz and/or nevirapine and who had plasma HIV-1 RNA<400 copies/mL. Resistance to rilpivirine, etravirine, tenofovir and emtricitabine by bulk sequencing was performed on extracted HIV-1 DNA from whole blood collected at the time of trial inclusion. RESULTS: Reverse transcriptase gene amplification was successful in 128/169 (76%) individuals and 95% of HIV-1 were infected with subtype B. Rilpivirine RAMs were detected in 41 (32%) individuals, with highest frequency for the mutations Y181C/I/V (18%), K101E/P (7%) and E138A/G/K/Q/R/S (6%) and the association L100I+K103N/S (5%). Etravirine RAMs were detected in five (4%) individuals. Resistance to emtricitabine, tenofovir and at least one drug included in the combination of tenofovir/emtricitabine/rilpivirine were detected in 72 (56%), 12 (9%) and 88 (69%), respectively. CONCLUSIONS: In individuals with suppressed viraemia under antiretroviral therapy (ART), but who had been previously exposed to an efavirenz and/or nevirapine-based regimen, rilpivirine RAMs are frequent and etravirine RAMs are rare. This finding suggests that the switch to a rilpivirine-based regimen should not be recommended.

Augmentation with amisulpride for schizophrenic patients non-responsive to risperidone monotherapy.

INTRODUCTION: The combination of antipsychotic drugs is a therapeutic resource in clinical practice. This study aimed to evaluate the efficacy and security of adding amisulpride in patients who at least partially responded to risperidone. METHODS: A 3-month, open, observational study was undertaken to evaluate the effectiveness of adding amisulpride in subjects who scored at least 25 on the brief psychiatric rating scale (BPRS) after risperidone monotherapy. Patients were evaluated with BPRS, the Clinical Global Impressions Severity of Illness scale (CGI-S) and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale (UKU) at baseline, 1 and 3 months. RESULTS: Coadjuvant treatment with amisulpride achieves a statistically significant improvement in mental status over a period of 3 months when measured with BPRS, CGI and UKU scales. The response rate was 70 (45%) in the oral risperidone and 74 (28%) in the parenteral risperidone groups. DISCUSSION: The addition of amisulpride could lead to an improvement in schizophrenia symptoms in patients that do not, or only partially, respond to risperidone. Further research is required into alternative therapies for poor responders.

Calcium renal lithiasis and bone mineral density. Importance of bone metabolism in urinary lithiasis.

CONTEXT: Calcium Nephrolithiasis is a multifactorial disease; in its pathophysiology is involved various minerals and metabolic factors that may be altered, including bone and phosphor-calcium metabolism. OBJECTIVE: To establish the scientific evidence and demonstrate the relationship between calcium nephrolithiasis and bone mineral density loss, through the use of bone turnover markers, serum and urinary metabolites. EVIDENCE ACQUISITION: We performed a PubMed literature review using different MeSH Terms like "Nephrolithiasis", "Bone mineral density", "Urinary stones", "Calcium", Bone resorption" and "Bone formation", with different combinations. We only selected articles with abstracts in English or Spanish and discarded clinical cases and articles with inappropriate statistical study. A total of 40 articles were selected. EVIDENCE SYNTHESIS: In different studies reviewed have been observed that patients with hypercalciuria have a higher bone mineral density loss with respect to normocalciuric. Among patients with calcium stones (normocalciuric or hypercalciuric), there is loss of bone mineral density, being more evident in patients with stones and hypercalciuria. This mineral density loss is marked and important in patients with recurrent calcium stones. Increased markers like fasting calcium/creatinine and ß-CrossLaps are determinant of nephrolithiasis and mineral density loss in these patients. CONCLUSION: We recommend perform markers of bone turnover and fasting calcium/creatinine in patients with recurrent calcium stones by the significant presence of bone mineral density loss, with a level of evidence III.

Predictive factors for mortality in patients with methicillin-resistant Staphylococcus aureus bloodstream infection: impact on outcome of host, microorganism and therapy.

Mortality related to methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) remains high, despite changes in the epidemiology. To analyze the current predictive factors for mortality we conducted a prospective study in a large cohort of patients with MRSA-BSI from 21 Spanish hospitals. Epidemiology, clinical data, therapy and outcome were recorded. All MRSA strains were analysed, including susceptibility to antibiotics and molecular characterization. Vancomycin MICs (V-MIC) were tested by the E-test and microdilution methods. Time until death was the dependent variable in a Cox regression analysis. Overall, 579 episodes were included. Acquisition was nosocomial in 59% and vascular catheter was the most frequent source (38%). A dominant PFGE genotype was found in 368 (67%) isolates, which belonged to Clonal Complex (CC)5 and carried SCCmecIV and agr2. Microdilution V-MIC50 and V-MIC90 were 0.7 and 1.0 mg/L, respectively. Initial therapy was appropriate in 66% of episodes. Overall mortality was observed in 179 (32%) episodes. The Cox-regression analysis identified age >70 years (HR 1.88), previous fatal disease (HR 2.16), Pitt score >1 (HR 3.45), high-risk source (HR 1.85) and inappropriate initial treatment (HR 1.39) as independent predictive factors for mortality. CC5 and CC22 (HR 0.52 and 0.45) were associated with significantly lower mortality rates than CC8. V-MIC ≥1.5 did not have a significant impact on mortality, regardless of the method used to assess it.

Eficacia y durabilidad de la electroestimulación percutánea del nervio tibial posterior en el tratamiento de la vejiga hiperactiva idiopática con procedimiento enfermero asociado / No disponible

El objetivo de este estudio es evaluar la respuesta a la electroestimulación percutánea del nervio tibial posterior (PTNS), en un grupo de pacientes con diagnóstico de vejiga hiperactiva y determinar cuándo se debe reiniciar un nuevo tratamiento. Se presenta una cohorte retrospectiva de 53 mujeres, de edades comprendidas entre 30 y 82 años, con una media de 61,5 años. Todas fueron sometidas a estudios urodinámicos antes y después del tratamiento, realizados de acuerdo a las recomendaciones de la Sociedad Internacional de Continencia (ICS).Paralelamente se diseñó y realizó un procedimiento enfermero a lo largo de todas las sesiones del tratamiento, orientado a la enseñanza de ejercicios y técnicas conductuales para el control voluntario de la micción. Se ha utilizado el programa SPSS 15.0 para el tratamiento estadístico de los datos, llegando a la conclusión de que la PTNS es segura, efectiva y una buena opción en pacientes con vejiga hiperactiva refractaria al tratamiento médico o con intolerancia al mismo y que el tratamiento debería reiniciarse después de 24 meses. La tasa de pacientes con reducción superior al 50% en los episodios de micción fue mayor que el reportado por otros autores. Los conocimientos adquiridos por medio del procedimiento enfermero utilizado ayudan a mantener la mejoría, aunque se ha observado que después de un tiempo se relajan estos hábitos (AU)

The purpose of this study is to assess the answer to the (PTNS) for a group of patients diagnosed with, determining the optimal timing for reinitiating a new treatment plan. This retrospective cohort study included a total of 53 patients (range 30-82 years; median age 61.5 years), with an age range from 30 to 82 years; with an median age of 61.5 years. They underwent urodynamic studies before and after the treatment, conducted in accordance with the recommendations set forth by the International Continence Society (ICS). Simultaneously a nursing procedure was designed and performed all along the sessions of the treatment, oriented towards training exercises and behavioural techniques for voluntary control of urination. Patients with > 50% reduction in episodes of urination were higher than those reported by other authors. Knowledge gained throughout the Nursing procedure help to maintain improvement, although it has been observed that these habits get relaxed after some time (AU)

Efectos terapéuticos de la hipoterapia en la parálisis cerebral: una revisión sistemática / Therapeutic effects of hippotherapy in cerebral palsy: a systematic review

Objetivo: Revisar la evidencia científica existente respecto al tratamiento de hipoterapia en niños con parálisis cerebral en función de diferentes variables. Métodos Se ha realizado una búsqueda bibliográfica en las bases de datos Pubmed/Medline, Web of Knowledge, Cochrane, PEDro, Enfispo, y en los metabuscadores Trip Data Base y Excelencia clínica. Los términos utilizados en la búsqueda fueron: equine-assisted therapy, cerebral palsy, hippotherapy y horseback riding, combinados generalmente con el operador boleano AND. Resultados Después de eliminar artículos duplicados de las diferentes bases de datos se obtuvieron 25 artículos. Siete de ellos eran revisiones sistemáticas o metaanálisis, 7 eran ensayos clínicos y 11 estudios eran series clínicas no controladas o estudios descriptivos. La calidad de la evidencia científica proporcionada por los estudios utilizados en esta revisión sistemática fue de nivel I para 7 de ellos, de nivel III (evidencia científica proporcionada buena a regular) para otros 7 artículos, y de nivel VIII (evidencia científica proporcionada pobre) para los restantes 11 artículos. Discusión Las principales limitaciones encontradas en los estudios revisados han sido el tamaño muestral reducido, el uso de herramientas de valoración no estandarizadas y/o la heterogeneidad de los protocolos de tratamiento utilizados. Conclusión Resulta difícil encontrar evidencia científica del tratamiento de hipoterapia en niños con parálisis cerebral como consecuencia de diferentes factores, como son los reducidos tamaños muestrales utilizados por los estudios, la diversidad de escalas de valoración y de protocolos de tratamiento utilizados (AU)

Objective: To review the current scientific evidence regarding hippotherapy treatment in children with cerebral palsy through the analysis of different study variables.Methods: A bibliographic research of Pubmed/Medline, Web of Knowledge, Cochrane, PEDro,Enfispo databases and Trip Data Base and Excelencia clínica metasearchers was carried out. The terms used in the search were: Equine-Assisted Therapy, Cerebral Palsy, Hippotherapy and Horseback riding, usually combined with the Boolean operator AND. Results: After eliminating duplicated articles in the different databases, 25 articles were found. Seven of them were systematic reviews or meta-analysis, 7 articles were clinical trials and11 studies were uncontrolled clinical series or descriptive studies. The quality of scientific evidence provided by the studies used in this systematic review was level I for seven of them, level III for seven articles (scientific evidence provided good to regular) and level VIII (scientificevidence provided poor) for the remaining eleven articles. Discussion: The main limitations found in the studies reviewed have been small sample sizes, use of non-standardized assessment tools and/or heterogeneity of the treatment protocolsused. Conclusion: It is difficult to find scientific evidence regarding hippotherapy treatment in children with cerebral palsy due to different factors such as the small sample sizes used in the studies, the diversity of assessment scales and treatment protocols used (AU)

An historical view of the pineal gland and mental disorders.

Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was "the three cells of the brain", in which the pineal gland was even called the "appendix of thought". The pineal gland could also be associated with the boom, during this period, of certain legends about the "stone of folly". But the most relevant psychopathological role of this organ arrived with Descartes, who proposed that it was the seat of the human soul and controlled communications between the physical body and its surroundings, including emotions. After a period of decline during which it was considered as a mere vestigial remnant of evolution, the link between the pineal gland and psychiatric disorders was definitively highlighted in the 20th century, first with the use of glandular extracts in patients with mental deficiency, and finally with the discovery of melatonin in 1958. The physiological properties of melatonin reawakened interest in the relationship between the pineal gland and mental disorders, fundamentally the affective and sleep disorders, which culminated in the development of new pharmacological agents acting through melatonergic receptors (ramelteon and agomelatine).

Gastro-intestinal Chagas disease in migrants to Spain: prevalence and methods for early diagnosis.

Each year in Spain, the number of Latin American immigrants who present with chronic Trypanosoma cruzi infection increases. Although gastro-intestinal abnormalities are not as common as cardiomyopathy in such infection, they can still lead to an impaired quality of life. In a recent study based in Madrid, the frequencies of gastro-intestinal involvement in a cohort of Latin American immigrants infected with T. cruzi, and the role of early diagnostic techniques in the detection of such involvement, were explored. Between January 2003 and April 2009, all Latin Americans who attended the Tropical Medicine Unit of the Hospital Universitario Ramón y Cajal were tested for T. cruzi infection, in IFAT and ELISA. Each subject found both IFAT- and ELISA-positive was considered to be infected (chronically) and checked for symptoms indicative of Chagas disease. Each infected subject giving informed consent was investigated further, using an electrocardiogram, an echocardiogram and oesophageal manometry. Between January 2003 and June 2008, every infected subject who consented was also explored using a barium swallow and barium enema. After July 2008, however, only subjects showing oesophageal and/or colonic symptoms were investigated in this manner. Of the 248 patients found infected with T. cruzi, 118 underwent oesophageal manometry, 75 a barium enema and 48 a barium swallow. Thirteen (11%) showed evidence of oesophageal involvement (incomplete relaxation of the lower oesophageal sphincter; three cases) or bowel involvement (five cases of dolichosigma, three of dolichocolon and two of megacolon). Only six of these 13 had any gastro-intestinal symptoms (all six were suffering from constipation). None of the barium swallows revealed any pathology. It appears that oesophageal manometry can reveal mild abnormalities not detected by barium swallow, even in asymptomatic patients, while barium enemas are useful in the detection of colonic involvement.

Chagas disease in Latin American migrants: a Spanish challenge.

Chagas' disease affects millions in Latin America and is the leading cause of cardiomyopathy and death due to cardiovascular disease in patients aged 30-50 years. As a consequence of immigration it has settled in several European countries, where besides imported cases, autochthonous infections arise through vertical transmission and blood/organ donation. All Latin American immigrants who attended our Unit were screened for T. cruzi infection (ELISA and IFAT ± PCR). An ECG and echocardiogram were requested for all positive patients, and oesophageal manometry, barium swallow and barium enema were requested according to patient symptoms. All patients under 50 years without severe cardiac involvement and who had not received correct treatment previously were treated with benznidazole 5 mg/kg/day for 60 days. Patients were followed-up with serology and PCR 1 month after treatment ended and every 6 months thereafter. A total of 1146 Latin Americans were screened for T. cruzi (357 positive serology results). The typical patient profile was a Bolivian female, of rural origin, in her fourth decade of life, without evidence of visceral involvement. Treatment tolerance was poor, with 29.7% discontinuing treatment due to adverse reactions. Among those with adverse reactions (52%), the most frequent were cutaneous hypersensitivity (68.7%), gastrointestinal upset (20%) and nervous system disturbances (16.2%). T. cruzi infection is no longer limited to Latin America. Poor treatment tolerance can limit current treatment options. More epidemiological data are necessary to estimate the magnitude of a problem of great relevance for public health and health resource planning.

Fumagillin for treatment of intestinal microsporidiosis in renal transplant recipients.

We report 10 cases of intestinal microsporidiosis due to Enterocytozoon bieneusi in renal transplant (RT) recipients who were treated with fumagillin. All patients presented with afebrile subacute diarrhea (median of 2 weeks), associated with abdominal cramps (n = 5), and weight loss (n = 6), a mean of 68 months after RT. The diagnosis was made by the identification of microsporidial spores in stools with the use of appropriate staining and confirmed by a specific polymerase chain reaction assay for E. bieneusi in 7 patients. Median CD4 cell count was 292 cells/mm(3). All patients received a median of 14 days of oral fumagillin (20 mg tid), and four patients also discontinued or tapered their immunosuppressive regimen (mycophenolate mofetil in 3, and azathioprine in 2). Clinical symptoms resolved rapidly with the clearance of microsporidial spores from stools in all patients. A severe but reversible thrombocytopenia was observed in one patient during fumagillin therapy, and another patient presented with abdominal cramps. Trough levels of tacrolimus measured in seven patients dropped below 5 ng/mL in six of them after 7-14 days of fumagillin. Intestinal microsporidiosis can cause subacute diarrhea in RT recipients. Fumagillin is an effective treatment with an acceptable safety profile, but monitoring of tacrolimus levels is warranted.

Asociación entre los niveles de ácido fólico con biomarcadores de riesgo cardiovascular en atletas de alto rendimiento / Association beetwen folic acid levels with cardiovascular risk biomarkers in high performance athletes

INTRODUCCIÓN: La deficiencia de ácido fólico y de vitamina B12 disminuye el rendimiento físico. Los atletas de alto rendimiento podrían tener una ingesta insuficiente de vitaminas del grupo B si se alimentan con dietas monótonas o de bajo consumo energético. Se ha demostrado que niveles bajos de homocisteína (Hcy) en sangre están normalmente asociados con la vitamina B12 y fólico, y con un menor riesgo cardiovascular, mostrándose el entrenamiento relacionado intenso con la hiperhomocisteinemia (HHcy) (> 12 mg / mL). OBJETIVO: Valorar el estado nutricional en B12 y fólico, y la situación cardiovascular en una muestra de deportistas de élite y estudiar el efecto de una suplementación en la población, donde el riesgo cardiovascular está presente. METODOLOGÍA: El estudio se ha llevado a cabo con 14 jugadores profesionales de balonmano > 18años, llevando un seguimiento durante dos meses de entrenamiento intermitente intenso y suplementado con 200 mg/d de ácido fólico y 2,5μg/d de vitamina B12. Tanto al inicio como a los dos meses y a los cuatro meses se valoró la ingesta de ácido fólico y vitamina B12 (mediante recordatorio de 72h y el software Nutriber®), y se determinaron los niveles de B12, fólico y Hcy mediante enzimoinmunoensayo(AU)

CONCLUSIÓN /DISCUSIÓN: Tanto la ingesta de vitamina B12 como su nivel plasmático fueron adecuados. La ingesta de fólico estaba de acuerdo con las RDIs en humanos sanos, pero por debajo de la ingesta diaria recomendada para deportistas (300μg/d) en el 14,3% de los sujetos al comienzo del estudio; ninguno se mostró deficiente después de la suplementación. Otros autores recomiendan un consumo más alto de ácido fólico para entrenamiento intermitente intenso (400- 500 mg/d), y teniendo en cuenta estas recomendaciones, nuestros resultados muestran un 50-85,5%, respectivamente, de deportistas con una ingesta deficiente de ácido fólico. Aun así, los niveles de ácido fólico en plasma se encuentran dentro de los niveles de referencia (ref. 4,2-19,9 ng/ml), aunque se encuentra una asociación negativa significativa entre los niveles plasmáticos de fólico y Hcy (p <0,05). ¿Cuál es la ingesta real recomendada de fólico y vitamina B12 en deportistas con entrenamiento intermitente intenso? Los atletas de élite deben ser controlados mediante un exhaustivo asesoramiento y seguimiento nutricional y clínico. Es necesario el ajuste de las recomendaciones de vitamina B12 y ácido fólico para optimizar el rendimiento deportivo y prevenir problemas cardiovasculares comunes asociados(AU)

INTRODUCTION: The deficiency of folic acid and vitamin B12 reduced physical performance. High performance athletes may have an insufficient intake of vitamins of group B if they are fedmonotonous diets with low energy consumption. It has been shown that low levels of homocysteine (Hcy) levels are usually associated with vitamin B12 and folic acid, and reduced cardiovascular risk, showing the intense training associated with hyperhomocysteinemia (HHcy) (> 12 mg / mL). OBJECTIVE: To assess the nutritional status of B12 and folate, and cardiovascular status in a sample of elite athletes and to study the effect of supplementation in the population where cardiovascular risk is present. METHODS: The study was conducted with 14 professional handball players > 18 years, followed for two months of intense intermittent training and supplemented with 200 mg / d of folic acid and 2.5μg /d of vitamin B12. At baseline and at two months and four months we evaluated the intake of folic acid and vitamin B12 (72h-recall and Nutriber ® software), and determined the levels of B12, folate and Hcy by enzyme immunoassay(AU)

CONCLUSION / DISCUSSION: Both the intake of vitamin B12 and its plasma level was adequate. Folate intake was according to the RDIs in healthy humans, but below the recommended daily intake for athletes (300μg / d) in 14.3% of subjects at baseline, none were poor after the supplementation. Other authors recommend a higher intake of folic acid to intense intermittent training (400 - 500 mg /d), and taking into account these recommendations, our results showed a 50-85.5%, respectively, Athletes with an inadequate intake of folic acid. Still, folic acid levels in plasma are within the reference levels (ref. 4.2 to 19.9 ng / ml), although there is a significant negative association between plasma levels of folate and Hcy (p <0.05). What is the recommended intake of folic real and vitamin B12 in intense intermittent training athletes? Elite athletes should be monitored by a comprehensive nutritional counseling and clinical monitoring. Adjustment is needed on the recommendations of vitamin B12 and folic acid to optimize athletic performance and prevent cardiovascular problems commonly associated(AU)

Deficiencia de cobre en un colectivo y factores asociados / Copper deficiency in a collective and associated factors

INTRODUCCIÓN: El cobre ejerce un papel esencial como nutriente en el organismo, se necesita un aporte diario mínimo a partir de alimentos o suplementos para el buen funcionamiento de la actividad celular. Está presente en todos los tejidos y participa activamente en la síntesis de la hemoglobina e influye sobre la absorción del hierro. Su deficiencia provoca anemia, diarrea, debilidad generalizada, alteraciones respiratorias y lesión cutánea, teniendo un papel esencial como protector frente el estrés oxidativo, un importante papel en el sistema inmunológico y una gran influencia sobre la expresión de numerosos genes. OBJETIVO: Valorar el estatus de cobre en un grupo de personas adultas sanas procedente de un colectivo de personas sanas adultas, estableciéndose tanto los niveles de ingesta como los niveles plasmáticos y eritrocitarios de este mineral, y estudiando una posible relación con otros parámetros. METODOLOGÍA: El estudio se realizó en una muestra de 90 sujetos de edades comprendidas entre 21 y 59 años (31 hombres y 53 mujeres), todos de la provincia de Granada. El criterio de inclusión se basó en la aceptación de los sujetos a participar en el estudio y no presentar ningún tipo de patología que pudiera afectar su situación clínico-nutricional. El Cu se analizó mediante Espectrofotometría de Absorción Atómica (AAS) en muestras de eritrocito y plasma mineralizadas por vía húmeda. Se aplicó un cuestionario de frecuencia de consumo, y mediante programa informático Nutriber (Mataix, yGarcia Diz 2006)1 se obtuvo el % de RDA. Se contó con la aceptación del Comité ético y el consentimiento informado(AU)

RESULTADOS: La ingesta media recomendada de cobre en la población adulta española es de 1,1mg/día. Los resultados obtenidos muestran ingestas del cobre <2/3 de IR en un 58,2% de la población estudiada, de los cuales el 53,6% son hombres y el 60,8% son mujeres. En plasma, se observaron valores deficientes en cobre en el 25% de la población total, siendo el 29% hombres y el 22,6 % mujeres. En eritrocito, el 21,4% de la población general presentaron deficiencia de cobre, siendo el 28,8% hombres y el 18,9% mujeres. Se encontró una correlación significativa positiva entre la ingesta de macronutrientes y los niveles de cobre en ingesta, así como entre la ingesta de cobre y la de hierro, cinc, magnesio, calcio y selenio. Igualmente, se observa una correlación positiva significativa entre los niveles de cobre en plasma y los niveles de cinc (p<0,02). CONCLUSIÓN: Según los resultados obtenidos, podemos concluir que son necesarios estudios recientes y detallados que aborden la valoración del estatus de cobre de una manera más integral, desde una evaluación pormenorizada de la ingesta hasta la determinación de biomarcadores específicos de cobre, teniendo en cuenta su participación en numerosas reacciones biológicas celulares que pueden alterarse por la deficiencia(AU)

INTRODUCTION: The copper has a crucial role as a nutrient in the body, you need a minimum daily intake from food or supplements for the proper functioning of cellular activity. Is present in all tissues and is actively involved in the synthesis of hemoglobin and influences iron absorption. Deficiency causes anemia, diarrhea, general weakness, respiratory and skin lesion, having an essential role as a protector against oxidative stress, an important role in the immune system and a great influence on the expression of numerous genes. OBJECTIVE: To assess copper status in a group of healthy adults from a group of healthy adults, establishing both the levels of intake and plasma and erythrocyte levels of this mineral, and isexploring a possible relationship with other parameters. METHOD: The study was conducted in a sample of 90 subjects aged between 21 and 59 years (31 men and 53 women), all of the province of Granada. The inclusion criteria was based on the acceptance of individuals to participate in the study and did not show any pathology that could affect clinical and nutritional status. Cu was analyzed by Atomic Absorption Spectrometry (AAS) in erythrocytes and plasma samples mineralized by wet. We applied a food frequency questionnaire, and through software Nutriben (Mataix, and Garcia Diz 2006)1 was obtained by the% of RDA. It was accepted by the Ethics Committee and informed consent(AU)

RESULTS: The average recommended intake of copper in the Spanish adult population is 1.1 mg /day. The results show copper intakes <2 / 3 of IR in 58'2% of the population studied, of which 53'6% are men and women 60'8%. In plasma, were found deficient in copper values in 25% of the total population, being 29% male and 22.6% women. In erythrocytes, 21.4% of the general population showed copper deficiency, with 28.8% men and 18.9% women. There was a significant positive correlation between macronutrient intake and levels of copper intake, as well as between dietary copper and iron, zinc, magnesium, calcium and selenium. Similarly, there is a significant positive correlation between plasma copper levels and zinc levels (p <0.02). CONCLUSION: According to the results, we conclude that studies are needed to address recent detailed assessment of copper status in a more comprehensive, since a thorough assessment of intake to the identification of specific biomarkers of copper, taking into account participation in numerous cellular biological reactions that may be altered by the deficiency(AU)

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia.

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3-16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.

Discrepancy between antibiotics administered in acute exacerbations of chronic bronchitis and susceptibility of isolated pathogens in respiratory samples: multicentre study in the primary care setting.

A national multicentre prevalence study was undertaken to determine the bacterial strains associated with mild-to-moderate acute exacerbations of chronic bronchitis (AECB) in the primary care setting and the susceptibility of isolated pathogens to different antimicrobials usually prescribed to these patients. All samples were processed by a central reference laboratory. Microdilution tests were carried out to establish the minimum inhibitory concentration (MIC) of various antimicrobials. A double-disk test was performed to establish the macrolide resistance phenotype in Streptococcus pneumoniae. Tests to detect the presence of beta-lactamase in Haemophilus influenzae and Moraxella catarrhalis and polymerase chain reaction to detect the presence of ermB and mefA genes in S. pneumoniae isolates were also performed. A total of 1537 patients were included in the trial and 468 microorganisms were isolated from sputum samples, with the most frequent isolates being S. pneumoniae (34.8%), M. catarrhalis (23.9%) and H. influenzae (12.6%). Resistance rates of pneumococci were 47.2% for penicillin, 1.2% for amoxicillin, 34.3% for macrolides (87.5% of which showed high-level resistance), 13.6% for cefuroxime/axetil and 4.2% for levofloxacin. No bacterial isolates showed resistance to telithromycin. Empirical antibiotic treatment was prescribed to 98.3% of patients, including macrolides to 36.6%, amoxicillin with or without clavulanic acid to 32.3% and fluoroquinolones to 16.1%. In conclusion, S. pneumoniae was the most frequently isolated bacteria in patients with mild-to-moderate AECB. Despite the high rates of resistance of pneumococci to macrolides, they continue to be the most widely used antibiotics in primary care to treat AECB.

Economic evaluation of the antibiotic treatment of exacerbations of chronic bronchitis and COPD in primary care.

This was an observational and economic survey performed in primary care practices throughout Spain to assess the effectiveness and direct medical costs derived from antibiotic treatment of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) in primary care. A total of 252 physicians included 1456 valid patients, 80% were male and the mean age was 68.2 years (SD = 9.8). The antibiotic treatment administered was moxifloxacin in 575 (39.5%), amoxicillin/clavulanate in 460 (31.6%) and clarithromycin in 421 (28.9%). No significant differences were found in clinical and demographic characteristics between treatment arms. The 30-days follow-up visit was completed by 1097 (75%) patients, who were therefore valid for economic evaluation. During follow-up, 440 new medical visits were generated, 69 patients required attendance in emergency wards (6.3%) and 22 were hospitalised (2%). The overall mean cost of exacerbation was Euro 118.58 [95% confidence interval (CI) = Euro 92.2-144.9] and Euro 52.44 (44.2%) were due to therapeutical failure. The mean cost of exacerbation was Euro 111.46 (95% CI = Euro 73.4-149.5) for patients treated with moxifloxacin, Euro 109.45 (95% CI = Euro 68.2-150.7) for those treated with amoxicillin/clavulanic acid and Euro 138.95 (95% CI = Euro 89.4-188.5) for patients receiving clarithromycin. In conclusion, a significant number of patients require new medical interventions after ambulatory treatment of exacerbations of CB or COPD. The mean cost of an exacerbation was Euro 118.58 and failure was responsible for 44.2% of the total cost of exacerbation.

[Principles of phototherapy and its use in cancer patients]. / Principios de la fototerapia y su aplicación en el paciente oncológico.

Phototherapy (PHOT) is a therapeutic option whose effectiveness is determined by its capability to destroy cells, with the benefit of discrimination between healthy and diseased tissue. It is based on the previous administration of a drug acting as a photosensitizing agent, and subsequent laser radiation, which brings about cellular destruction. The objective of this study is to review the principles and methods on which this therapeutic modality is based, as well as its use in the cancer field. To this end, we reviewed the MEDLINE database from 2000 to March 2003. Results show a limited effectiveness in small-sized tumours alone, and as a palliative measure, rather than as a healing therapy.