Efficacy of Once-Daily Ophthalmic Bilastine for the Treatment of Allergic Conjunctivitis: A Dose-Finding Study

Background and objectives: Bilastine is a nonsedating second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Our study aimed to evaluate the optimal dose, efficacy, and safety of a newly developed once-daily preservative-free ophthalmic formulation of bilastine for allergic conjunctivitis. Methods: Our phase 2, single-center, double-masked, randomized trial compared the efficacy of 3 doses of a bilastine ophthalmic formulation (0.2%, 0.4%, and 0.6%) with that of vehicle for the treatment of allergic conjunctivitis. The primary efficacy endpoint was the reduction in ocular itching. The Ora-CAC Conjunctival Allergen Challenge model was used to assess ocular and nasal symptoms at the onset of action (15 minutes) and at 8- and 16-hours after treatment. Tolerance and safety were also evaluated. Results: A total of 121 adults with seasonal and/or perennial ocular allergy were randomized. Bilastine ophthalmic formulations 0.2%, 0.4%, and 0.6% were significantly superior (P>.001) to vehicle for the treatment of ocular itching at 3, 5, and 7 minutes after challenge at onset of action (15 minutes) and at 8 hours after treatment. Bilastine 0.6% was also effective at 16 hours after treatment. Treatment differences for bilastine 0.6% were statistically significant (P<.001) compared to vehicle at all timepoints for tearing, eyelid swelling, and nasal symptoms. No relevant adverse events were observed. Conclusions: All the tested ophthalmic bilastine doses were efficacious for rapid reduction of ocular itching. The 0.6% formulation was effective up to 16 hours after treatment, making it suitable for once-daily administration. The new formulation was safe and well tolerated (AU)

Therapeutic benefits of niraparib tosylate as radio sensitizer in esophageal squamous cell carcinoma: an in vivo and in vitro preclinical study

PurposeEsophageal squamous cell carcinoma is associated with high morbidity and mortality rate for which radiotherapy is the main treatment modality. Niraparib, a Poly (ADP-ribose) polymerase 1 inhibitors (PARPi) was previously reported to confer radiosensitivity in different malignancies including non-small cell lung cancer. In this study, we assessed the in vivo ability of niraparib in conferring radiosensitivity to esophageal squamous cell carcinoma cells.Materials and methodsIn this study, KYSE-30 and KYSE-150 cell lines were selected as in vivo esophageal squamous cell carcinoma models. The experimental groups were: niraparib tosylate alone, radiotherapy alone, control (no intervention), and combination therapy (radiotherapy + niraparib tosylate). Cell cytotoxicity assay, colony formation assay, flow cytometry, immunofluorescence, Western blotting, immunohistochemistry, lentivirus transfection analysis, and xenograft models were used for confirming radiosensitizing ability of niraparib and to investigate the possible cellular mechanism involved in radiosensitization.ResultsThe colony formation efficiency of the combination group was significantly much lower than that of the single radiation group (P < 0.01). Cell cytotoxicity assay demonstrated a significant reduction in proliferation of irradiated cells after treatment with niraparib tosylate compared to niraparib tosylate alone (P < 0.01). Cell apoptosis significantly increased in the combination group compared to either niraparib tosylate or radiotherapy alone (P < 0.01). Rate of tumor suppression rate was significantly high in the combined treatment group (P < 0.01) but, significantly decreased in nude mice. Western blot and lentivirus infection model suggested overexpression of FANCG genes to confer radiosensitivity.ConclusionThese results suggest that the synergistic effect of niraparib tosylate and radiation may be related to the down-regulation of FANCG. (AU)

Baricitinib y tofacitinib en pacientes con artritis reumatoide: resultados de práctica clínica habitual / Baricitinib and tofacitinib in patients with rheumatoid arthritis: results of regular clinical practice

Objetivo: Objetivo principal: describir la efectividad y seguridad debaricitinib y tofacitinib en pacientes diagnosticados de artritis reumatoideen nuestro centro. Objetivo secundario: analizar si existen diferenciasentre ambos fármacos en práctica clínica real.Método: Estudio observacional retrospectivo de 2 años de duraciónque incluyó pacientes diagnosticados de artritis reumatoide en tratamientocon baricitinib o tofacitinib en nuestro centro durante al menos 6 meses.Bases de datos: historia clínica electrónica, aplicativo informático dedispensación a pacientes externos. Variables recogidas: demográficas,factores de mal pronóstico, tratamiento previo, duración de tratamiento,tratamiento concomitante, escala DAS28, número de articulaciones inflamadas y dolorosas, escala visual analógica del dolor, suspensión deltratamiento y reacciones adversas. Evaluación de la efectividad: disminución en la escala DAS28, articulaciones inflamadas y dolorosas y escalavisual analógica del dolor a los 6 y 12 meses de iniciado el tratamiento.Evaluación de la seguridad: detección de reacciones adversas. Análisisestadístico: prueba t-student.Resultados: Se evaluaron 44 pacientes, 20 (70% mujeres) recibierontratamiento con baricitinib, 24 (95,8% mujeres) con tofacitinib. Baricitinibredujo la puntuación en la escala DAS28 en 2,3 y 1,7 a los 6 y 12 meses.Tofacitinib en 2 y 1,9 respectivamente. Baricitinib redujo el número de articulaciones inflamadas y dolorosas en 7 a los 6 y 12 meses, tofacitinib en 4 las inflamadas y 6 las dolorosas. Baricitinib redujo la puntuación en la escala visual analógica del dolor en 7,8 y 6,8; tofacitinib en5 y 6 a los 6 y 12 meses. El 40% de los pacientes con baricitinib y el62,5% con tofacitinib precisaron tratamiento con corticoides. El 10% delos pacientes con baricitinib y el 25% de los pacientes con tofacitinibsuspendieron el tratamiento por ineficacia. (AU)

Objective: Main objective: Describe the effectiveness and safety ofbaricitinib and tofacitinib in patients diagnosed with rheumatoid arthritis inour hospital. Secondary objective: Analyse whether there are differencesbetween the two drugs in routine clinical practice.Method: Two-year retrospective study of patients diagnosed with rheumatoid arthritis treated in our hospital with baricitinib and tofacitinib forat least 6 months. Databases: Electronic medical record and outpatientmedication dispensing software. Variables collected: Demographic variables, poor prognosis factors, previous treatment, duration of treatment,concomitant treatment, DAS28, number of swollen and painful joints, painvisual analogy scale, treatment discontinuation, and adverse reactions.Effectiveness evaluation: Decreases in the DAS28 scale, the number ofswollen and painful joints, and the pain Visual Analogy Scale at 6 monthsand 12 months after starting treatment. Safety evaluation: Detection ofadverse reactions. Statistical analysis: Student t-test.Results: A total of 44 patients were evaluated. Of these, 20 (70% women)received treatment with baricitinib and 24 (95.8% women) received tofacitinib. Baricitinib reduced the DAS28 by 2.3 and 1.7 at 6 months and12 months, respectively, and tofacitinib reduced the scale by 2 and 1.9 at6 months and 12 months, respectively. Baricitinib reduced the numberof swollen and painful joints by 7 at both 6 months and 12 months, and tofacitinib reduced the number of swollen and painful joints by 4 and 6at 6 months and 12 months, respectively. Baricitinib reduced the VisualAnalogy Scale score by 7.8 and 6.8 at 6 months and 12 months, respectively, and tofacitinib reduced the score by 5 and 6 at 6 months and12 months, respectively. (AU)

Treating patients with ALK-rearranged non-small-cell lung cancer: mechanisms of resistance and strategies to overcome it

Anaplastic lymphoma kinase (ALK) rearrangement is detected in 3-7% of patients with non-small-cell lung cancer. Crizotinib is an ALK inhibitor, which was approved in 2011 for the treatment of ALK-positive lung cancer. Despite the initial enthusiasm, most of the patients develop resistance within the first year of treatment. The main mechanisms are secondary mutations and bypass track activation. Moreover, crizotinib has low penetration into the central nervous system. The need to overcome these limitations has led to the development of second-generation inhibitors that have better effectiveness against crizotinib-resistant mutations and brain metastases. Ceritinib and alectinib are the only approved drugs of this group. Many ongoing trials try to define the most appropriate agent for the treatment of ALK-positive lung cancer depending on the responsible mechanism. This review focuses on the current data regarding the potential mechanisms of resistance to ALK inhibitors and the strategies to overcome it (AU)

No disponible

Comparación de bolus de fentanilo con perfusión de remifentanilo en el control de larespuesta hemodinámica a la laringoscopia e intubación orotraqueal: estudioprospectivo, randomizado y doble ciego / Bolus administration of fentanyl vs continuous perfusion of remifentanil for control of hemodynamic response to laryngoscopy and orotracheal intubation: a randomized double-blind trial

OBJETIVOS: Comparar la eficacia y seguridad del fentanilocon remifentanilo en la prevención de la respuestahemodinámica asociada a la laringoscopia directa eintubación orotraqueal, y su repercusión sobre la saturaciónperiférica de oxígeno en mujeres normotensasprogramadas para cirugía ginecológica.MATERIAL Y MÉTODO: Estudio clínico prospectivo enpacientes ASA I-II sometidas a cirugía ginecológica. Sedistribuyeron de forma aleatoria en dos grupos: grupoR, remifentanilo 1 μg Kg–1 min–1 hasta la intubación ygrupo F, fentanilo 2 μg Kg–1. Para la inducción anestésicautilizamos etomidato (0,3 mg Kg–1) y bromuro derocuronio (0,6 mg Kg–1). Se realizaron siete medicionesseriadas de la presión arterial sistólica, diastólica ymedia, frecuencia cardiaca y saturación periférica deoxígeno durante los periodos: control, desnitrogenación,postinducción, postintubación y posteriormente cada dosminutos tres determinaciones consecutivas.RESULTADOS: Se incluyeron 54 pacientes. El grupo R mostróun efecto estadísticamente significativo de atenuación dela respuesta hemodinámica postintubación tanto en la presiónarterial (p = 0,0001), como en la frecuencia cardiaca(p = 0,031) respecto de su valor basal. Sin embargo, con elgrupo del fentanilo (grupo F), no se observó dicho efecto protector.No se observaron diferencias en la saturación periféricade oxígeno en ambos grupos durante el estudio.CONCLUSIONES: A las dosis utilizadas, el remifentanilocomparativamente con el fentanilo, ofrece mayor controlhemodinámico. No se observaron efectos secundarios enambos grupos atribuibles a los opiáceos(AU)

OBJETIVES: To compare the efficacy and safety offentanyl and remifentanil in the prevention ofhemodynamic responses to direct laryngoscopy andorotracheal intubation, and to compare the effects ofthese techniques on peripheral blood oxyhemoglobinsaturation in normotensive women undergoingscheduled gynecologic surgery.MATERIAL AND METHODS: Prospective clinical trial inASA 1-2 patients undergoing gynecologic surgery. Thepatients were randomized to 2 groups: the remifentanilgroup received a perfusion of 1 μg·kg-1·min-1 untilintubation whereas the fentanyl group received a bolusdose of 2 μg·kg-1. Etomidate (0.3 mg·kg-1) and rocuroniumbromide (0.6 mg·kg-1) were used for anesthetic induction.Seven serial measurements of systolic, diastolic, and meanarterial pressure were recorded in addition to heart rateand peripheral blood oxyhemoglobin saturation at thefollowing times: baseline, denitrogenation, postinduction,and 3 more times at consecutive 2-minute intervals.RESULTS: Fifty-four patients were enrolled. Astatistically significant attenuation of the postintubationhemodynamic response was observed in the remifentanilgroup. The effect was evident on arterial pressure(P=.0001) and heart rate (P=.031) with respect tobaseline values. That protective effect was not seen in thefentanyl group. No differences in peripheral bloodoxyhemoglobin saturation were observed.CONCLUSIONS: Remifentanil provides greaterhemodynamic control than fentanyl at the doses utilized.No adverse effects attributable to these opioids wereobserved in either group(AU)

Remifentanilo intravenoso para analgesia del trabajo del parto / Intravenous remifentanyl for labor analgesia

La analgesia con remifentanilo intravenoso podría serla primera alternativa a las técnicas regionales cuandoéstas se encuentran contraindicadas.OBJETIVO: Revisión sistemática de la bibliografía disponiblesobre el uso de remifentanilo como analgesia delparto. Método: Búsqueda en MEDLINE (enero 1995-marzo 2009) y revisión de bibliografía de las publicacionessobre la analgesia obstétrica con remifentanilo.RESULTADOS: Se encontraron 37 referencias con untotal de 281 embarazadas tratadas con remifentanilo. Enla mayoría de los casos las pacientes mostraron descensoen el dolor referido y alto grado de satisfacción, sinefectos secundarios graves en las madres o neonatos.Comparándolo en ensayos clínicos con meperidina y óxidonitroso, el remifentanilo obtuvo mejores resultados enanalgesia y menores efectos secundarios.CONCLUSIÓN: La analgesia con remifentanilo intravenosoes una alternativa más eficaz y segura que otras técnicasno regionales en la analgesia obstétrica. Aún debeestablecerse el sistema óptimo de administración y se precisanestudios más amplios de seguridad materno-fetal(AU)

BACKGROUND: Intravenous remifentanil may be the preferredanalgesic when regional techniques are contraindicated.OBJETIVE: To perform a systematic review on the use ofremifentanil for analgesia in labor.METHODS: We searched MEDLINE (January 1995-August 2007) for studies on obstetric analgesia withremifentanil.RESULTS: We found 32 references representing the use ofremifentanil in 257 women in labor. In most cases, patientsreported relief of pain and a high level of satisfaction, with nosevere side effects in mothers or neonates. When compared withmeperidine and nitrous oxide in clinical trials, remifentanilprovided better analgesia with fewer adverse effects.CONCLUSION: Analgesia with intravenous remifentanil ismore effective and safer than other alternatives to regionalanalgesic techniques in obstetrics. Nevertheless, the optimumsystem for infusing the drug must be established and furtherstudies of maternal and fetal safety should be carried out(AU)

Consideraciones anestésicas en un paciente con déficit de pantotenato cinasa (enfermedad de Hallervorden-Spatz) para estimulación cerebral profunda / Anesthesia considerations for deep-brain stimulation in a patient with type-2 pantothenate kinase deficiency (Hallervorden-Spatz disease)

La neurodegeneración asociada al déficit de pantotenatocinasa es una entidad autosómica recesiva secundariaa las mutaciones del gen pantotenato cinasa 2(PANK2). Clínicamente se caracteriza por anormalidadesprogresivas del movimiento y demencia. El tratamientomédico de la enfermedad es limitado y la distoníasuele ser refractaria, por lo cual la cirugíaestereotáctica con colocación de electrodos cerebralesprofundos es una opción terapéutica cada vez más usadaen estos pacientes. Describimos una paciente de 32 añosde edad con distonía severa asociada a déficit dePANK2. Fue programada para tomografía computarizadaestereotáctica y colocación bilateral de electrodos ennúcleo pálido medial, bajo anestesia general para tratarla distonía debilitante y la rigidez generalizada asociadaa su enfermedad. Durante la intervención se realizó elmantenimiento anestésico con propofol, rocuronio yremifentanilo en perfusión, sin ninguna incidencia a destacardurante el procedimiento. Tras la intervención lapaciente fue trasladada a la unidad de cuidados intensivosbajo sedación farmacológica con remifentanilo paraproceder a una educción lentamente progresiva. Lapaciente pudo ser dada de alta tras la colocación delgenerador y en el seguimiento posterior se ha evidenciadomejoría de los movimientos distónicos(AU)

Neurodegeneration associated with pantothenate kinasedeficiency is an autosomal recessive condition caused bymutations in the pantothenate kinase 2 gene (PANK2).Clinical characteristics include progressive motorimpairment and dementia. Medical treatment is limited andthe dystonia tends to be refractory, making stereotacticsurgery with placement of deep-brain electrodes an optionthat is being adopted with greater frequency in thesepatients. We report the case of a 32-year-old woman withsevere dystonia associated with PANK2 protein deficiency.The patient was scheduled for stereotactic bilateralplacement of electrodes in the medial globus pallidus,guided by computed tomography and under generalanesthesia, to treat the debilitating dystonia and generalizedstiffness associated with her condition. Anesthesia wasmaintained with propofol, rocuronium and remifentanil inperfusion during the intervention, which was uneventful.After the procedure, the patient was transferred to theintensive care unit and sedation was provided withremifentanil to allow slow, gradual emergence fromanesthesia. The patient was discharged from hospital afterplacement of the implanted pulse generator, and subsequentfollow-up showed improvement of the dystonia(AU)

Estudio de la respuesta al estrés en dos técnicas analgésicas (remifentanilo continuo frente a fentanilo en bolos) valorando diferentes marcadores (citocinas, proteína C reactiva y cortisol) en el intra y postoperatorio de histerectomías abdominales / Stress response under continuous infusion of remifentanil compared to bolus doses of fentanyl assessed by levels of cytokines, C-reactive protein, and cortisol during and after abdominal hysterectomy

OBJETIVOS: La cirugía y los métodos anestésicos tienen efectos inmuno-moduladores sobre la respuesta hemodinámica y el estrés. Vamos a comparar los efectos que dos regímenes analgésicos intraoperatorios pueden tener en pacientes sometidas a histerectomías abdominales. MATERIAL Y MÉTODOS: Estudio clínico randomizado y prospectivo a doble ciego en pacientes ASA I-II sometidas a histerectomías abdominales bajo anestesia general balanceada. Las pacientes (n = 29) fueron divididas en dos grupos de forma aleatoria. En uno de ellos se realizó analgesia con remifentanilo en perfusión y rescate analgésico con morfina y AINEs. En el otro se efectuó analgesia convencional con fentanilo en bolos según valores hemodinámicos. Se recogieron mediciones puntuales a nivel basal, incisión quirúrgica, 1ª hora, 4ª hora y 24 horas de citocinas pro-inflamatorias (IL-6), anti-inflamatorias (IL-10), cortisol y proteína C-reactiva (ProtCr). RESULTADOS: No se apreciaron diferencias significativas entre ambos grupos respecto a los marcadores estudiados. En cada grupo y para los diferentes momentos recogidos se produjeron cambios significativos respecto a los niveles basales. Para Il-6 e IL-10 este aumento fue significativo (p < 0,05) a la 4ª hora; en el caso del cortisol, las diferencias fueron significativas a la 1ª y 4ª hora. Finalmente, la ProtCr tuvo aumentos significativos a las 24 horas. CONCLUSIONES: En nuestro estudio, a diferencia de otros ensayos clínicos, no se han observado diferencias en respuesta al estrés quirúrgico (valorada mediante el análisis de citoquinas pro y anti-inflamatorias, cortisol y PCR) entre estas dos técnicas analgésicas (AU)

OBJECTIVES: Surgery and anesthetic method have immunomodulating effects on hemodynamic response and stress. We compared the effects of 2 intraoperative analgesic regimens on patients undergoing abdominal hysterectomy. MATERIAL AND METHODS: We conducted a randomized double-blind trial in ASA 1 and 2 patients undergoing abdominal hysterectomy under balanced anesthesia. Twenty-nine patients were randomized to 2 groups. One group received analgesia by infusion of remifentanil plus morphine and nonsteroidal anti-inflammatory drugs as rescue medications; the other received conventional analgesia with bolus doses of fentanyl according to changes in hemodynamic variables. We measured levels of proinflammatory (interleukin [IL]-6) and anti-inflammatory (IL-10) cytokines, cortisol, and C-reactive protein preoperatively, at incision, and at 1, 4 and 24 hours after surgery. RESULTS: There were no significant differences between the 2 groups in terms of the markers studied at baseline. In each group, however, there were significant changes from baseline at the various points in time. IL-6 and IL-10 levels were significantly elevated (P<.05) at 4 hours. The changes in cortisol levels were significantly different at 1 and 4 hours. Finally, there were significant increases in C-reactive protein at 24 hours. CONCLUSIONS: Unlike other clinical trials, our study detected no differences between the 2 techniques in response to surgical stress evaluated by analyzing concentrations of pro- and anti-inflammatory cytokines, cortisol, and C-reactive protein (AU)

Analgesia del trabajo de parto con remifentanilo por vía intravenosa mediante un sistema de analgesia controlada por el paciente (PCIA) en un caso de esclerosis múltiple / Intravenous patient-controlled analgesia with remifentanil for labor and childbirth in a woman with multiple sclerosis

No disponible

No disponible

Cirugía fetal y procedimientos anestésicos / Anesthetic procedures during fetal surgery

No disponible

No disponible

Manejo anestésico para la realización de mediastinoscopia en un caso de hipertensión pulmonar severa / Anesthetic management for mediastinoscopy in a patient with severe pulmonary hypertension

No disponible

No disponible

Anestesia con remifentanilo para timectomía toracoscópica en paciente pediátrico con miastenia gravis / Anesthesia with remifentanil for thoracoscopic thymectomy in a girl with myasthenia gravis

No disponible

Remifentanilo en bolos para inducir apnea y bradicardia necesarias para la realización de coronariografía-tcmd en un paciente pediátrico / Remifentanil: bolus doses to induce apnea and bradycardia for coronary arteriography in a pediatric patient

No disponible

No disponible

Risperidona y acontecimientos adversos cerebrovasculares en los pacientes ancianos con demencia / Risperidone and cerebrovascular adverse in elderly patients with dementia

No disponible

Respuesta. Risperidona y acontecimientos adversos cerebrovasculares en los pacientes ancianos con demencia / Reply. Risperidone and cerebrovascular adverse in elderly patients with dementia

No disponible