Off-label and unlicensed drug use in a Spanish Neonatal Intensive Care Unit / Utilización de medicamentos fuera de ficha técnica y sin licencia en una Unidad de Cuidados Intensivos Neonatales española

Objective: To describe off-label and unlicensed drugs in clinical practice in a Neonatal Intensive Care Unit (NICU). Method: The design of the study was a descriptive and retrospective three months research in a NICU of a Spanish University Hospital. All prescriptions were classified as approved, off-label and unlicensed drug used, according to the information available on the Summary of Product Characteristics. Off-label drugs prescriptions were divided into four groups (dose, frecuency, age and indication of use) depending on the reason of disconformity. Results: Forty-one neonates were included (46.3% premature patients) and a total of 273 drug prescriptions were evaluated. Of them, 53.1% (145) were classified as an approved drug prescriptions, 41.4% (113) were off-label use and 5.5% (15) were unlicensed drugs. 90.2% of the patients (37/41) received at least one off label prescription, with a median of 3 (range 1-7). Age was the foremost reason for off-label use (42.5%), followed by dose (31.0%), frecuency (16.8%) and dose-frecuency off-label drug use (8.8%). The last place was reserved for off-label drug use by indication (0.9%). Group J (corresponding with antiinfectives for systemic use) was the most frecuently prescribed, with ampicillin (18.6%) and gentamicin (16.8%) as the drugs most commonly use as off-label prescriptions. Finally, caffeine citrate was the unlicensed drug most frecuently prescribed. Conclusion: Off-label and unlicensed drug use prescriptions in our NICU clinical practice are highly frecuent as other authors have previously published in other countries where they were studied. Although there are few studies in newborn patients, both off-label and unlicensed drug prescriptions are commonly recomended in Paediatrics Guidelines (AU)

Objetivo: Describir la utilización de medicamentos fuera de ficha técnica (FFT) y sin licencia en una Unidad de Cuidados Intensivos Neonatales (UCIN). Método: Estudio descriptivo y retrospectivo realizado durante tres meses en la UCIN de un hospital público español. Las prescripciones se clasificaron según la ficha técnica oficial en tres grupos: dentro de ficha técnica, FFT y sin licencia. Las prescripciones FFT se clasificaron según la razón por la que no se ajustaban a ella en cuatro grupos: dosis, frecuencia, edad e indicación. Resultados: Se incluyeron 41 neonatos (46,3% prematuros) y 273 prescripciones. De ellas, el 53,1% (145) se prescribieron según ficha técnica, el 41,4% (113) FFT y el 5,5% (15) sin licencia. El 90,2% de los pacientes (37/41) recibieron al menos un tratamiento FFT, con una media de 3 (rango 1-7). En el 42,5% de los casos la razón por la cual se consideró al fármaco FFT fue la edad, en el 31,0% la dosis, en el 16,8% la frecuencia, en el 8,8% la dosis y la frecuencia y en el 0,9% la indicación. El grupo terapéutico prescrito con más frecuencia fue el J (antiinfecciosos para uso sistémico), con ampicilina (18,6%) y gentamicina (16,8%) como fármacos más prescritos FFT. El fármaco sin licencia con mayor número de prescripciones fue la cafeína citrato. Conclusiones: En nuestra UCIN la utilización de fármacos FFT y sin licencia es muy habitual y similar a la de otros países. La mayoría de las prescripciones analizadas no disponen de estudios específicos en neonatos, aunque sí está ampliamente recomendado su uso en las guías de práctica clínica pediátricas (AU)

Off-label prescription of drugs at hospital / Prescripción hospitalaria de medicamentos en condiciones fuera de ficha técnica

OBJECTIVES: To develop a procedure for management of off-label medications, and to analyze the treatments, indications, and hospital units which will request them more frequently, as well as which variables will have an impact on the authorization decision, and its economic impact. METHODS: A procedure was designed where clinicians would complete request forms and the Hospital Unit would prepare reports assessing their efficacy, safety, convenience, and cost. The request forms for the past five years were analyzed. RESULTS: A total of 834 applications were received, and 88.1% of these were accepted. The authorization rates were higher for Paediatric Units (95.7% vs. 86.6%; p < 0.05, Student's t test) when spending increased. CONCLUSIONS: The responsibility for assessing off-label prescriptions has fallen on the Pharmacy Unit. It has not been demonstrated that the quality of evidence represents a decisive variable for approval of treatment; on the other hand, age and cost have demonstrated a significant impact

OBJETIVOS: Desarrollar un proceso de gestión de medicamentos en condiciones fuera de ficha técnica y analizar los tratamientos, indicaciones y unidades clínicas que los solicitan, qué variables influyen en la decisión de autorización y su impacto económico. MÉTODOS: Se diseñó un procedimiento según el cual los clínicos cumplimentarían las solicitudes, el Servicio de Farmacia redactaría los informes valorando su eficacia, seguridad, conveniencia y coste, y la dirección médica tomaría la decisión de aceptar o no su uso. Se analizaron las solicitudes de los últimos cinco años. RESULTADOS: Se recibieron 834 solicitudes, autorizándose el 88,1%. Las tasas de autorización fueron mayores para los Servicios Pediátricos (95,7% frente a 86,6%; p < 0,05). Las razones por las que las prescripciones se consideraron fuera de ficha técnica fueron: diferente indicación (73,2%), combinación diferente (10,2%), línea diferente (8,6%) y edad diferente (8%). El 73,4% de las solicitudes fueron de antineoplásicos, siendo rituximab (120) y bevacizumab (103) los más prescritos. La calidad de la evidencia que avalaba las prescripciones fue moderada-baja, aunque sin demostrar relación directa con la probabilidad de aprobación (p = 0,413). El coste de los medicamentos aprobados fue de 8.567.537 € y el ahorro teórico de los denegados 2.268.642 €. El porcentaje de autorización disminuyó según aumentó el gasto de manera estadísticamente significativa (p < 0,05, test t de Student). CONCLUSIONES: La responsabilidad de evaluación de las prescripciones fuera de ficha técnica ha recaído en los Servicios de Farmacia. La calidad de la evidencia no ha demostrado ser una variable decisiva para la aprobación de los tratamientos. En cambio, la edad y el coste sí que han demostrado influir significativamente

Factor structure and psychometric properties of the TFEQ in morbid obese patients, candidates to bariatric surgery.

BACKGROUND: To analyze the factor structure and psychometric properties of the TFEQ in a morbid obese Spanish sample of bariatric surgery candidates. METHOD: Multi-trait/ multi-item analyses and alpha coefficients were conducted to test the convergent /discriminant validity and the internal consistency reliability. Principal components analyses (varimax) were used to explore the factor structure. Sub-group factor analyses by gender, age and body mass index (BMI) were conducted to identify unstable items. RESULTS: The internal structure of the original TFEQ factors was unsatisfactory, especially the Disinhibition Scale. Most Disinhibition and Hunger items were grouped on one factor labeled “Dysregulation Eating”. Cognitive Restraint was split into two factors. The first one, related to the behavioral component of Restraint, labeled “Restrained Behaviour” and the second one related to weight and eating concerns called “Predisposition to Restraint”. CONCLUSIONS: The original factor structure of the TFEQ was not replicated. A revised 23-item instrument, representing the three new derived factors is offered as a valid screening instrument for severely obese patients.

Factor structure and psychometric properties of the TFEQ in morbid obese patients, candidates to bariatric surgery / Estructura factorial y propiedades psicométricas del TFEQ en pacientes con obesidad mórbida candidatos a cirugía bariátrica

BACKGROUND: To analyze the factor structure and psychometric properties of the TFEQ in a morbid obese Spanish sample of bariatric surgery candidates. METHOD: Multi-trait/ multi-item analyses and alpha coefficients were conducted to test the convergent /discriminant validity and the internal consistency reliability. Principal components analyses (varimax) were used to explore the factor structure. Sub-group factor analyses by gender, age and body mass index (BMI) were conducted to identify unstable items. RESULTS: The internal structure of the original TFEQ factors was unsatisfactory, especially the Disinhibition Scale. Most Disinhibition and Hunger items were grouped on one factor labeled «Dysregulation Eating». Cognitive Restraint was split into two factors. The first one, related to the behavioral component of Restraint, labeled «Restrained Behaviour» and the second one related to weight and eating concerns called «Predisposition to Restraint». CONCLUSIONS: The original factor structure of the TFEQ was not replicated. A revised 23-item instrument, representing the three new derived factors is offered as a valid screening instrument for severely obese patients

ANTECEDENTES: analizar la estructura factorial y las propiedades psicométricas del TFEQ en una muestra española de obesos mórbidos candidatos a cirugía bariátrica. MÉTODO: se realizó un análisis multi-rasgo/multi-ítem y de coeficientes alpha para probar la validez convergente/discriminante y la consistencia interna. Se utilizó un análisis de componentes principales (varimax) para estudiar la estructura factorial. Se llevó a cabo también un análisis de factores de subgrupos por género, edad e IMC para identificar aquellos ítems inestables. RESULTADOS: la estructura interna original de los 3 factores TFEQ fue insatisfactoria, especialmente en la escala de Desinhibición. La mayoría de los ítems de Desinhibición y Hambre se agruparon en un mismo factor denominado «Desregulación en la ingesta». La Restricción Cognitiva se dividió en dos factores. El primero, relacionado con el componente de Restricción, se denominó «Restricción Activa» y el segundo, relacionado con el peso y las preocupaciones de la ingesta, se llamó «Predisposición a la Restricción». CONCLUSIONES: la estructura factorial original del TFEQ no se replica. En este artículo se presenta un instrumento revisado de 23 ítems, que representa los tres nuevos factores derivados, como instrumento de cribado válido para pacientes obesos graves

Synthesis, self-assembly and photophysical properties of oligo(2,5-dihexyloxy-1,4-phenylene vinylene)-block-poly(ethylene glycol).

We describe the synthesis and characterization of a family of diblock copolymers with 5 units of a dihexyloxy-phenylenevinylene block (OHPV) connected to a series of poly(ethylene glycol) (PEG) chains of different average lengths (12, 45 and 115 PEG units: OHPV5-b-PEG12, OHPV5-b-PEG45, OHPV5-b-PEG115). All three polymers underwent self-assembly in ethanol, a good solvent for the PEG units, but poor for the OHPV segment. The nature of the structures formed depends sensitively on the length of the PEG block. OHPV5-b-PEG115 formed long fiber-like micelles of uniform width, whereas OHPV5-b-PEG45 formed fragile broad ribbons. We also obtained thin ribbons with OHPV5-b-PEG12 but they tend to fold and twist upon themselves. The structures obtained were characterized by transmission electron microscopy (TEM) and atomic force microscopy (AFM), as well as by wide-angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC). In addition, their photophysical properties were examined by UV-vis, steady state fluorescence and fluorescence decay measurements. The results of these experiments indicate that the OHPV groups pack differently in the fiber-like micelles of OHPV5-b-PEG115 than in the lamellar structures formed by OHPV5-b-PEG45.

Dynamic self-assembly of polycationic clusters based on cyclodextrins for pH-sensitive DNA nanocondensation and delivery by component design.

The ability of cyclodextrin-based polycationic cluster to undergo reversible DNA condensation and release in a physiologically useful pH window has been finely tuned by the installation of a capping xylylene moiety at the secondary face of the cyclooligosaccharide. This strategy can be exploited advantageously in the design of self-assembling nonviral gene-delivery systems from molecular entities.

Influence of the macroring size on the self-association thermodynamics of cyclodextrins with a double-linked naphthalene at the secondary face.

The conformational properties and aggregation behavior of two selectively modified cyclomaltooligosaccharides (cyclodextrins, CDs) containing a double-linked 1,8-dimethylnaphthalene cap-like moiety at the secondary face, namely, 2(I),3(I)-O-(1,8-dimetylnaphthalene-α,α'-diyl)-per-O-Me-α- and -γ-cyclodextrins (NmαCD and NmγCD, respectively), in water and in organic solvents were investigated. Both CD derivatives self-associated in water to form dimer species, but the characteristics of the dimerization process and of the resulting dimer strongly depended on the size of the macrocycle. Dimerization constants, thermodynamic parameters upon association, and information about the preferred conformations of the monomer and dimer CD structures were obtained by using NMR, UV-vis, steady-state and time-resolved fluorescence, and circular dichroism experimental techniques, as well as molecular mechanics (MM) and molecular dynamics (MD) simulations. The complexation of 1,8-di(methoxymethyl)naphathalene (oNy) and the heteroassociation of both NmCDs with their permethylated CD partners (mCDs), lacking the aromatic cap, were examined. In addition, the influence of the size of the chromophore moiety on the thermodynamics of self-association was also assessed by comparison of the results obtained for the new naphthalene derivatives with those of the 2(I),3(I)-O-(1,2-xylylene)-modified CD analogues (XmCDs).

Association between bacteremia due to Streptococcus gallolyticus subsp. gallolyticus (Streptococcus bovis I) and colorectal neoplasia: a case-control study.

BACKGROUND: The association between bacteremia by Streptococcus gallolyticus subsp. gallolyticus (SGG) and colorectal neoplasia (CRN) is well established but the frequency of the association varies widely in different studies. We conducted a case-control study to assess the association between SGG bacteremia and CRN. METHODS: An analysis of all SGG bacteremias was performed during the period 1988-2011. The frequency of CRN in patients with SGG bacteremia was compared with the frequency of CRN in a symptomatic control group of patients matched at a 1:2 ratio for gender and age (±3 years) without S. bovis bacteremia and personal history of CRN and with increased risk of CRN (by the presence of symptoms, signs, or test suspicious of colonic pathology or by family history of CRN). RESULTS: One hundred nine cases of SGG bacteremia were detected (mean age, 66 years; 87% male). Colonoscopy was performed in 98 cases, diagnosing 69 cases of CRN: 57 adenomas (39 advanced adenomas) and 12 invasive carcinomas. Only 4 cases had suspected CRN before the blood culture. The prevalence of CRN was higher in patients with SGG bacteremia than in the 196 control patients (70% vs 32%; odds ratio [OR], 5.1; 95% confidence interval [CI], 3.0-8.6). This difference was not significant when comparing nonadvanced adenomas (19% vs 12%), but we found significant differences in advanced adenomas (40% vs 16%; OR, 3.5; 95% CI, 2.0-6.1) and invasive carcinomas (12% vs 5%; OR, 2.9; 95% CI, 1.2-6.9). CONCLUSIONS: The frequency of CRN among SGG infected patients is significantly increased compared with symptomatic age-matched controls, indicating that SGG infection is a strong indicator for underlying occult malignancy.

Study of the conformational and self-aggregation properties of 2I,3I-O-(o-xylylene)-per-O-Me-alpha- and -beta-cyclodextrins by fluorescence and molecular modeling.

Steady-state and time-resolved fluorescence techniques were used to study the behavior of 2I,3I-O-(o-xylylene)-per-O-Me-alpha- and -beta-cyclodextrins in aqueous solution, based on the fluorescence of the bidentate xylylene moiety. Fluorescence decay profiles obtained upon excitation of the xylylene group were fitted to three-exponential decay functions. In addition to a fast component due to stray and/or scattered light, two other components ascribed to the monomer and dimer species, respectively, were identified. The dimer/monomer ratio increases with concentration and decreases with temperature, which is in agreement with an enthalpy-driven association process. The corresponding dimerization equilibrium constants (KD) were obtained from nonlinear regression analysis of the plots of tau against [CD] in the 5-45 degrees C range. A linear van't Hoff analysis for KD allows us to obtain the DeltaH and DeltaS associated to dimer formation. Molecular mechanics as well as molecular dynamics calculations in the presence of water were also employed to study the conformational behavior of such secondary-face-substituted cyclodextrins and rationalize the dimerization processes.

One-pot regioselective synthesis of 2(I),3(I)-O-(o-xylylene)-capped cyclomaltooligosaccharides: tailoring the topology and supramolecular properties of cyclodextrins.

The alpha,alpha'-dibromo-o-xylylene cap has been installed at the secondary hydroxyls of a single glucopyranosyl residue in cyclodextrins in one pot and with total regioselectivity; the resulting cyclic ether acts as a removable hinge, allowing selective elaboration of the secondary face and modulating both the self-association and the inclusion capabilities of the hosts.

A new Cu(II)-5-(4-sulphophenylazo)-8-aminoquinoline complex used for copper determination in presence of gold and silver in water and mineral samples.

In this work, a characterization of reagent chromophore 5-(4-sulphophenylazo)-8-aminoquinoline [SPA] by IR and 1H RMN was carried out and a pK(a) value of 3.55+/-0.03 was found as well. An 1:2 stoichiometry for the Cu(II)-SPA complex was determined at pH 9 by Job and molar ratio methods. A value of 1.4 x 10(14) for the stability constant was also found. Based on the formation of this complex a new method for the copper determination in presence of gold and silver was developed by derivative spectrophotometry using a previous preconcentration on solid phase. In this method, the analytical measures were executed directly in the solid phase containing the complex. The Cu(II) reacts with the reagent chromophore SPA previously retained in the anionic exchange DEAE Sephadex A25. In this determination, the first derivative at 605 nm was used. The quantification range was between (3.2+/-0.3 x 10(-1)) x 10(-8) and (94.4+/-0.9) x 10(-8) mol L(-1) (3.2+/-0.3 x 10(-1)) x 10(-8), and (94.4+/-0.9) x 10(-8) mol L(-1). The repeatability expressed as RSD was between 1.1 and 2.0%. The method was applied successfully for the copper determination in mineral residuals and natural water samples. The results were consistent with those provided by ICP-mass spectrometry.

Ley 1551 de participación popular, comentarios y concordancias

Contiene: Ley de Participación Popular - De la Participación Popular - De los gobiernos municipales - De los recursos de la participación popular - La administración pública y Participación Popular.