Evolución clínica en recién nacidos con presunción de sepsis nosocomial tratados con cefazolina o vancomicina. Estudio de no inferioridad, aleatorizado, controlado / Clinical outcome of neonates with nosocomial suspected sepsis treated with cefazolin or vancomycin. A non-inferiority, randomized, controlled trial

Las infecciones nosocomiales persisten elevadas en las unidades de cuidados intensivos neonatales, lo cual motiva el muy frecuente uso de antibióticos. Nuestro objetivo fue evaluar la eficacia de la cefazolina frente a la vancomicina como terapia inicial en los recién nacidos con signos clínicos presuntivos de sepsis nosocomial probablemente causada por Staphylococcus coagulasa negativo. Métodos. Se incluyeron recién nacidos hospitalizados con signos clínicos muy probables de sepsis bacteriana nosocomial. Dos grupos fueron asignados aleatoriamente según el antibiótico utilizado en el inicio del tratamiento: grupo cefazolina (GC) o grupo vancomicina (GV). El análisis primario se realizó mediante la intención de tratamiento. La medida principal de resultado fue la evolución clínica de los neonatos en ambos grupos al final del tratamiento. Resultados. Se analizaron 109 recién nacidos, 52 en el GC y 57 en el GV. Las características basales fueron similares entre los grupos. El porcentaje de recién nacidos con evolución clínica adecuada fue de 92% en el GC y de 86% en el GV: diferencia de 6% (95% CI: de -7% a 19%, valor p de no inferioridad, p= 0,007). En el GC, fallecieron 7 recién nacidos (13,5%) y 11, en el GV (19,2%), diferencia no significativa (p= 0,45). Conclusión. En recién nacidos con sepsis nosocomial confirmada o altamente probable, la cefazolina no fue inferior a la vancomicina en el logro de un resultado clínico adecuado.

Evolución clínica en recién nacidos con presunción de sepsis nosocomial tratados con cefazolina o vancomicina. Estudio de no inferioridad, aleatorizado, controlado / Clinical outcome of neonates with nosocomial suspected sepsistreated with cefazolin or vancomycin. A non-inferiority, randomized, controlled trial

Las infecciones nosocomiales persisten elevadas en las unidades de cuidados intensivos neonatales, lo cual motiva el muy frecuente uso de antibióticos. Nuestro objetivo fue evaluar la eficacia de la cefazolina frente a la vancomicina como terapia inicial en los recién nacidos con signos clínicos presuntivos de sepsis nosocomial probablemente causada por Staphylococcus coagulasa negativo.Métodos. Se incluyeron recién nacidos hospitalizados con signos clínicos muy probables de sepsis bacteriana nosocomial. Dos grupos fueron asignados aleatoriamente según el antibiótico utilizado en el inicio del tratamiento: grupo cefazolina (GC) o grupo vancomicina (GV). El análisis primario se realizó mediante la intención de tratamiento. La medida principal de resultado fue la evolución clínica de los neonatos en ambos grupos al final del tratamiento. Resultados. Se analizaron 109 recién nacidos, 52 en el GC y 57 en el GV. Las características basales fueron similares entre los grupos. El porcentaje de recién nacidos con evolución clínica adecuada fue de 92% en el GC y de 86% en el GV: diferencia de 6% (95% CI: de -7% a 19%, valor p de no inferioridad, p= 0,007). En el GC, fallecieron 7 recién nacidos (13,5%) y 11, en el GV (19,2%), diferencia no significativa (p= 0,45). Conclusión. En recién nacidos con sepsis nosocomial confirmada o altamente probable, la cefazolina no fue inferior a la vancomicina en el logro de un resultado clínico adecuado.

Clinical outcome of neonates with nosocomial suspected sepsis treated with cefazolin or vancomycin: a non-inferiority, randomized, controlled trial.

BACKGROUND: Nosocomial infections are a major problem in Neonatal Intensive Care Units. Coagulase negative Staphylococcus (CONS) is the most common causative agent. We evaluated the efficacy of cefazolin versus vancomycin as initial therapy for neonates with presumptive clinical signs of nosocomial sepsis probably caused by CONS. METHODS: Hospitalized newborns infants with clinical signs of very probable bacterial sepsis were included. Two groups were randomly assigned according the initial antibiotic therapy: cefazolin group (CG) or vancomycin group (VG). The primary analysis was performed on an intention-to-treat basis. The main outcome measure was the clinical outcome of infants in both groups at the end of antibiotic treatment. RESULTS: We analyzed 109 newborns, 52 in CG and 57 in VG. Baseline characteristics were similar among groups. The percentage of neonates with adequate outcome was 92% in the CG and 86% in the VG: difference: 6% (95% CI: -7% to 19%, p-value non-inferiority, p = 0.007). Seven infants died in the CG (13.5%) and and 11 (19.2%) in the VG; no significant difference (p=0.45). CONCLUSION: Cefazolin was not inferior to vancomycin in achieving an adequate clinical outcome in newborn infants with confirmed or highly probable nosocomial sepsis.

Early detection of neonatal cholestasis by stool color card screening. / Detección precoz de la colestasis neonatal en las heces por el método de tamizaje con tarjetas colorimétricas.

The objective of this study was to identify, by early screening, one-month old infants with acholic or hypocholic stools for the early detection of biliary atresia and other causes of neonatal cholestasis. The study was essentially exploratory (observational, prospective, statistically underpowered and with no clinical intervention) and used a color card screening of all newborns attending the first month of life checkup from 1999 to 2002 in a public hospital in Argentina. Of 12 484 newborn infants, 4239 were examined at their first month of life checkup visit with the stool color card. Eighteen infants were identified with hypocholic stools, of whom only four were proven to have cholestasis. Although no case of biliary atresia was detected, screening by stool color cards proved useful for the detection of other causes of neonatal cholestasis.

El objetivo del presente estudio fue identificar, mediante el tamizaje precoz, a los lactantes de un mes de edad con deposiciones acólicas o hipocólicas, para la detección temprana de la atresia biliar y otras causas de colestasis neonatal. El estudio fue esencialmente exploratorio (observacional, prospectivo, sin potencia estadística y sin intervención clínica experimental), usando un método de tamizaje de las heces con tarjetas colorimétricas en todos los recién nacidos atendidos en el control de salud del primer mes durante el período 1999- 2002 en un hospital público de la Argentina. De los 12 484 recién nacidos, 4239 fueron atendidos en la visita del primer mes con la tarjeta colorimétrica. Se identificaron 18 niños con deposiciones hipocólicas, de los cuales solo 4 demostraron tener enfermedad colestásica. Si bien no se identificó ningún caso de atresia biliar, la prueba de tamizaje mostró ser de utilidad para la detección de otras causas de colestasis neonatal.

Preliminary clinical findings on NEUMUNE as a potential treatment for acute radiation syndrome.

5-androstenediol (5-AED) has been advanced as a possible countermeasure for treating the haematological component of acute radiation syndrome (ARS). It has been used in animal models to stimulate both innate and adaptive immunity and treat infection and radiation-induced immune suppression. We here report on the safety, tolerability and haematologic activity of 5-AED in four double-blinded, randomized, placebo-controlled studies on healthy adults including elderly subjects. A 5-AED injectable suspension formulation (NEUMUNE) or placebo was administered intramuscularly as either a single injection, or once daily for five consecutive days at doses of 50, 100, 200 or 400 mg. Subjects (n = 129) were randomized to receive NEUMUNE (n = 95) or the placebo (n = 34). NEUMUNE was generally well-tolerated; the most frequent adverse events were local injection site reactions (n = 104, 81%) that were transient, dose-volume dependent, mild to moderate in severity, and that resolved over the course of the study. Blood chemistries revealed a transient increase (up to 28%) in creatine phosphokinase and C-reactive protein levels consistent with intramuscular injection and injection site irritation. The blood concentration profile of 5-AED is consistent with a depot formulation that increases in disproportionate increments following each dose. NEUMUNE significantly increased circulating neutrophils (p < 0.001) and platelets (p < 0.001) in the peripheral blood of adult and elderly subjects. A dose-response relationship was identified. Findings suggest that parenteral administration of 5-AED in aqueous suspension may be a safe and effective means to stimulate innate immunity and alleviate neutropenia and thrombocytopenia associated with ARS.

An orally bioavailable synthetic analog of an active dehydroepiandrosterone metabolite reduces established disease in rodent models of rheumatoid arthritis.

Dehydroepiandrosterone (DHEA) treatment provides diverse anti-inflammatory benefits in rodent models of diseases, including rheumatoid arthritis (RA), but only limited benefits to patients. In rodents, DHEA is metabolized to (among others) androstene-3beta,7beta,17beta-triol (AET), which retains potent anti-inflammatory activity. 17Alpha-ethynyl-5-androstene-3beta,7beta,17beta-triol (HE3286) is a novel, metabolically stabilized, orally bioavailable derivative of AET. In the DBA mouse model of collagen-induced arthritis (CIA), once-daily oral treatments (gavage) with HE3286 (40 mg/kg), beginning at onset of disease, significantly decreased disease. Benefit was associated with reduction in joint inflammation, erosion, and synovial proliferation as measured by histological analysis and mRNA of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, IL-1beta, and IL-23. Significant benefit was also observed in the CIA model even when treatments were delayed until 7 days after the onset of arthritis. Furthermore, dose-dependent benefit was observed in the DBA mouse model of collagen antibody-induced arthritis, as well as reductions in IL-6 and matrix metalloproteinase-3 mRNA levels in joints at the peak of disease and at the end of the study. HE3286, in contrast to dexamethasone, was not immune-suppressive in several classic animal models of immune function. Instead, HE3286 treatment was associated with reduced nuclear factor-kappaB activation and in our previous studies, with increased regulatory T cells. We hypothesize that HE3286 may represent a novel, perhaps first-in-class, anti-inflammatory agent and may more fully translate the benefits of DHEA, heretofore largely limited to rodents, into treatments for human diseases, including autoimmune disorders such as RA.

Safety and activity of the immune modulator HE2000 on the incidence of tuberculosis and other opportunistic infections in AIDS patients.

Twenty-five AIDS patients were treated with HE2000, a synthetic adrenal hormone. The drug was well tolerated and safe and reduced both the incidence of tuberculosis coinfection by 42.2% (P < 0.05) and the cumulative incidence of opportunistic infections (P < 0.05). These results warrant further clinical investigation of HE2000.

Reduction of parasite levels in patients with uncomplicated malaria by treatment with HE2000.

16alpha-Bromoepiandrosterone (HE2000) is a synthetic androstane steroid that has immune effects in pre-clinical models of malaria, tuberculosis, and infection with human immunodeficiency virus. In pilot studies, 42 patients with confirmed uncomplicated Plasmodium falciparum malaria were treated with a seven-day course of HE2000 by either buccal administration or intramuscular injection. Of the 42 patients, 41 showed a 50% reduction in blood levels of parasites, the primary endpoint of the study. Of these, 32 (76%) cleared malaria parasites below detectable levels. All febrile patients became afebrile by the end of treatment. There was no reduction in gametocyte forms. Adverse events were transient and mild to moderate in intensity. The anti-malarial response was generally similar with either the intramuscular or buccal routes of administration. HE2000 shows a safety profile and pharmacologic activity worthy of further investigation to understand its role in the treatment of malaria, perhaps in combination with anti-malarial agents.

5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression.

We previously reported that five daily intramuscular doses of 5-androstenediol (AED), a naturally occurring adrenal steroid hormone, stimulated multilineage recovery of bone marrow in rhesus monkeys with radiation-induced myelosuppression after 4.0 Gy total body irradiation (TBI). Here we report the effect of AED on the survival of eighty rhesus macaques that received a 6.0 Gy dose of TBI in four sequential pilot studies. The drug was administered intramuscularly, based on body weight, 2-4 h after irradiation and continued once daily for a total of five injections. No clinical support in the form of antibiotics or transfusions was given to the animals at any time during the study. Five of the 40 (12.5%) treated animals died, compared to 13 of 40 (32.5%) of the animals in the control group (p=0.032). The combination of accumulated days of thrombocytopenia (<20,000 platelets/microL) up to day 14 (before the first death) together with treatment, accurately predicts mortality (p<0.001). The compound significantly reduced the duration of thrombocytopenia and neutropenia (p<0.01). The accumulation of days of neutropenia (ANC<500 cells/microL) up to day 14 plays no major role in predicting death. AED shows significant activity in irradiated primates with acute hematopoietic radiation syndrome.

Follow-up of children with autoimmune hepatitis treated with cyclosporine.

OBJECTIVES: To evaluate the effectiveness of cyclosporine in inducing and maintaining remission of the inflammatory process in autoimmune hepatitis, when used in combination with low doses of prednisone and azathioprine and to identify the prognostic factors associated with sustained remission. METHODS: Eighty-four patients with autoimmune hepatitis were consecutively recruited from 5 centers between January 1994 and March 2001. Cyclosporine was administered during the first 6 months. Thereafter, in patients with aminotransferase levels of lower than twice the normal values, prednisone and azathioprine were initiated. RESULTS: Normal aminotransferase levels were observed in 94.05% (79/84) of the patients, 72% of them within the first 6 months of treatment. Total serum bilirubin level of greater than 1.2 mg/dL and portal hypertension at diagnosis jointly predicted a significant delay in remission. Adverse effects related to cyclosporine remained mild and transient. Low doses of prednisone and standard doses of azathioprine were not implicated in relapse of the disease during the follow-up of any patient. CONCLUSIONS: This protocol allowed control of the liver inflammatory process and was well tolerated. The response to this immunosuppressive therapy can be predicted with accuracy. Factors delaying remission can be identified early at diagnosis and may contribute to the development of more effective treatment policies for this condition.

5-androstenediol stimulates multilineage hematopoiesis in rhesus monkeys with radiation-induced myelosuppression.

Total body ionizing irradiation (TBI) between 2-8 Gy causes the hematopoietic component of the acute radiation syndrome (ARS) in humans. Here we report on an exploratory study with 5-androstenediol (AED) in rhesus monkeys exposed to 4 Gy (60)Co gamma TBI. In this study, the effects of two formulations administered 3-4 h after irradiation were evaluated. After radiation, severe neutropenia (<500 neutrophils/microL), thrombocytopenia (<50,000 platelets/microL), and anemia (hemoglobin <8.0 g/dL) occurred in 6, 6, and 5 of the 6 control animals, respectively. In these 6 control animals, the median time to first day of each defined cytopenia was 8.5, 13, and 20 days and the median time to last occurrence was 22.5, 19.5 and 29.5 days, respectively. All treated groups had a decrease in the duration of severe neutropenia relative to vehicle control. All but one dosing regimen decreased the duration of thrombocytopenia and anemia. Five consecutive days of a 15 mg/kg intramuscular (IM) micro-particle preparation and a once weekly 15 mg/kg subcutaneous (SC) nanoparticle suspension generally provided the greatest radiation protection. AED, as a single agent, promotes multilineage hematopoietic recovery of the bone marrow. These data suggest that it may play an important therapeutic role in the management of acute radiation syndrome.

Maternal and perinatal factors influencing the duration of exclusive breastfeeding during the first 6 months of life.

The aim of this study was to evaluate the influence of certain factors on the duration of exclusive breastfeeding during the first 6 months of life. In 597 mothers, 26 variables were assessed during the postpartum period. The mothers were interviewed monthly by telephone about how they were feeding their babies. In 539 mothers (92.2%), complete data were obtained until the sixth month. At discharge, 1 month, 4 months, and 6 months, the frequency of exclusive breastfeeding was 97%, 83%, 56%, and 19%, respectively. The median duration was 4 months. A longer duration of exclusive breastfeeding was significantly associated with positive maternal attitudes toward breastfeeding, adequate family support, good mother-infant bonding, appropriate suckling technique, and no nipple problems. These associations persisted after controlling for maternal education and other confounding variables. Certain maternal factors related to a longer duration of exclusive breastfeeding can be identified in the maternity ward and might contribute to the development of more effective breastfeeding policies.

Conducta médica frente a lactantes y niños pequeños con infección respiratoria aguda alta: resultados de un estudio de observación / Medical attitudes with regard to infant and young children with upper airways acute infections: result of an observational study

La infección respiratoria aguda(IRA)alta es frecuente en la infancia,pero hay escasas publicaciones acerca del accionar del pediatra frente a esta afección.Objetivos.Determinar la conducta clínica del pediatra ante lactantes y niños con IRA alta y desarrollar una investigación en el consultorio.Diseño,observacional de corte transversal.Métodos.El estudio se realizó entre mayo y agosto de 1998.El criterio de inclusión para los pediatras fue ser socio de la región metropolitana de la Sap y para los pacientes,tener entre 3 meses y 2 años de edad con IRA alta.Aleatoriamente se elegieron 150 pediatras y cada uno de ellos debía incluir consecutivamente 10 pacientes.Resultados.10 pediatras no cumplían los criterios de inclusión,85 aceptaron participar y 63(45 por ciento)completaron el estudio.Estos incluyeron 636 pacientes,84 se eliminaron por errores en los formularios,por lo que 63 pediatras y 552 pacientes fueron la muestra analizada.El 62 por ciento de los pediatras efectuó residencia completa en pediatría,73 por ciento tenía actividad hospitalaria actual y 65 por ciento realizaba el Pronap(Programa Nacional de Actualización Pediátrica)La edad promedio de los pacientes fue de 12 meses(Ic 95 por ciento:11,7 -12,7)Los principales signos clínicos fueron:rinorrea:83 por ciento,tos:78 por ciento,fiebre:61 por ciento y congestión de fauces:55 por ciento,El diagnóstico más frecuente fue catarro de vía aérea superior(79 por ciento)Se efectuo otoscopia en el 93 por ciento de los pacientes,radiografías en el 3 por ciento y hemograma en el 1,3 por ciento.El 28 por ciento recibió antibiótico y el 6 por ciento medicación sintomática.Conclusiones.Participó el 45 por ciento de los pediatras invitados y su accionar mostró un adecuado empleo de la otoscopia,con pocos estudios complementarios y medicación.Este primer estudio en el consultorio presentó desafíos metodológicos,pero podría ser útil para motivar la creación de un programa nacional de investigación pediátrica en atención ambulatoria

Eficacia, tolerabilidad y seguridad de la ciclosporina para microemulsion en el tratamiento de la artritis reumatoidea activa: estudio abierto / Efficacy, tolerability and safety of cyclosporine for microemulsion in the treatment of the active rheumatoid arthritis: open study

La ciclosporina para microemulsión (cpm) ha sido ampliamente utilizada para el tratamiento de la ar- tritis reumatoidea (AR) con muy buenos resultados sobre la progresión del daño articular según ha sido informado por el grupo de estudio GRISAR1. Para evaluar eficacia, seguridad y tolerabilidad de la cpm en el tratamiento de la AR un grupo local de 12 centros (50 pacientes), realizó un estudio abierto, prospectivo (Neo-Ra-02), de seis meses de seguimiento. Los parámetros considerados para evaluar la eficacia fueron: modificación de la rigidez matutina, pruebas funcionales (índices de HAQ, Ritchie y Lee), de laboratorio y radiológicos (índice de Larsen). Los parámetros usados para evaluar la seguridad fueron: tensión arterial y determinaciones de laboratorio de función renal, hepática y análisis hematológico. Los criterios para la participación de los pacientes fueron: presencia de AR activa (según definición del ACR), estadios anatómicos y funcionales de Steinbrocker del I al III, evolución de la enfermedad no mayor de 5 años, ausencia de historia previa de hipertensión arterial, enfermedad renal o hepática y ausencia de uso de drogas modificadoras de la enfermedad en los dos meses anteriores al estudio. A las 4 semanas del tratamiento se verificó disminución estadísticamente significativa del dolor, rigidez matutina, scores de sensibilidad, entumecimiento articular e índice de Ritchie. No hubo incremento significativo de la creatinina, ni del ácido úrico séricos. Seis casos desarrollaron hipertensión arterial leve. La cpm demostró eficacia con mínima incidencia de efectos adversos (12 por ciento de hipertensión arterial leve) cuando su administración fue en dosis bajas y adecuadamente monitoreada.