Intrathecal administration of Ziconotide: does single-shot injection predict efficacy?

Introduction: Though a trial of intrathecal (IT) therapy should always be performed before implantation of a definitive intrathecal pump, there is no agreement as to how this test should be performed. Ziconotide is trialed in most of cases with continuous IT administration using implanted catheters. Unlike other intrathecal drugs, there is little experience with single bolus IT injections of ziconotide. The aim of the study is to assess the feasibility of single-shot IT trialing with ziconotide. Patients and methods: Eleven consecutive patients with chronic neuropathic intractable pain were trialed with a single IT bolus of 2.5 mcg of ziconotide. Pain and side effects are monitored for at least 72 hours after the injection. Depending on the response, a second injection is given a week later, with either the same dose (if VAS decreased ≥50% without side effects), a higher dose of 3.75 mcg (if VAS decreased <50% without side effects) or a lower dose of 1.25 mcg (if VAS decreased ≥50% but with side effects). If VAS decreased less than 50% and side effects occurred, no further injection was performed. When VAS decreased >50% without side effects after the first or the second dose, the result is confirmed by one more injection of the same dose one week later. The trial is considered positive if two successive injections provide a VAS decreased more than 50% without side effects. Results: Eleven patients (6 females and 5 males) were included. Nine patients experienced modest or no pain relief. Four of these had significant side effects (dizziness, nausea, vomiting or abdominal pain) and had no further injection. In the others 5, one patient retired from study and four received a second injection of 3.75 mcg. The trial was negative in all 5 cases because of side effects (dizziness, drowsiness, weakness, muscle cramps), the pain decreased in only 2 patients. Two patients experienced profound pain relief with an IT injection of 2.5 mcg. One patient had no side effects and the other had dizziness and drowsiness that disappeared with an injection of 1.25 mcg. Pain relief without adverse effects was confirmed with the second injection. The trial was considered positive for those two patients. Discussion and conclusion: The response rate of 18% (2/11) is consistent with the success rate of a continuous infusion trialing with an implanted catheter. Single-shot injection of ziconotide may therefore predict efficacy.

La utilización del concepto de ADN en nuestra sociedad: tecnociencia, frases hechas y errores científicos

La tecnología científica relacionada con el ADN y sus aplicaciones ha revolucionado nuestra sociedad. La información respecto a estos progresos se ha extendido rápidamente mediante los medios de comunicación. A su vez, las personas han incorporado conceptos de las tecnologías relacionadas con el ADN en su cosmovisión. La utilización de frases hechas basadas en el ADN ha tenido un gran éxito mediático, pero algunas de ellas contienen errores científicos graves. En este artículo se pretende mostrar dichos errores y posibles vías de actuación para corregirlos. Palabras clave: ADN, cosmovisión, frases hechas, selección natural, darwinismo, herencia de caracteres adquiridos, lamarckismo.

Treatment of Recurrent Hepatitis C after Liver Transplantation with PEG-Interferon and Ribavirin.

Background and aim: Recurrent hepati tis C is a major cause of morbidity and mortality after li ver transpl ant ati on (LT), and optimal treatm ent algorithms have yet to be defined. Here, we present our experience of 22 patients with recurrent hepatitis C treated in our institution .Patients and methods: Twenty-two patients with hi stology-proven recurrent hepati tis Cafter LT were treated since 2003. Treatment was ini ti ated with pegylated interferon-a2a 135 IIg per week and ribavirin 400 mg per day in the majority of patients, and subsequent doses were adapted individllally based on on-treatment virologieal responses and c1inical and/or biochemical si de effeets.Results: On an intention-to-treat basis, ustained virological re ponse(SVR) was achieved in 12/21 (54.5%) patie nts (5/12 [41 .6%], 2/3 [67%], 4/5 [80%] and 1/2 [50%] of patients infected with genotypes 1,2,3 and 4, respectively). Two patients experieneed relap e and 6 did not respond to treatm ent (NR). Treatment duration ranged from 24 to 90 weeks. It was stopped prematurely due to adverse events in 6/22 (27.2%) patients (with SVR achieved in 2 patients, NR in 2 patients, and death of 2 patients: one patient awaiting retransplantation and a second patient with HCV-HJV co-infection and fibrosing cholestat ic hepatiti s, nine months after transplantation). Of note, SVR was achi eved in a patient \Vi th combined liver and kidney transplantation. Importantly, SVR \Vas ach ieved in some patients despite the lack ofan early virological response or HCV RNA negativity at week 24. Darbepoetin a and fil ~,'rasti m were used in 36% and 18%, respectively.Conclusion: Individually adapted treatment of recurrent hepatitis C canachieve SVR in a substantial proponion ofLT patients. Conventional stopping rules do not apply in this setting so that prolonged therapy may be useful in selected patients.

Filosofia, ciencia social y cognición humana

Tradicionalmente, las ciencias sociales se han fundado en categorías de sentido común para describir la realidad, de modo que aceptan tácitamente el principio de la folk psychology, según el cual las personas actúan para conseguir aquello que desean, dadas unas creencias. Sin embargo, aunque los deseos y las creencias puedan ser causas de la acción, no hay modo de definir de forma conceptualmente independiente cada uno de estos elementos con el fin de elaborar leyes de la acción que sean informativas y empíricamente corregibles o ajustables. Se hace necesario substituir este sistema explicativo por otro que «divida la naturaleza por sus articulaciones». Alejada del fallido programa de investigación conductista, la ciencia social puede explorar nuevas vías para convertirse en una disciplina rigurosa equipada con un conjunto de teorías que permitan reorganizar las valiosas observaciones disponibles y sugerir nuevas hipótesis interdisciplinariamente integradas. Sin embargo, esto no ocurrirá en la medida en que no haya forma de escapar a las limitaciones de la folk psychology. El presente artículo trata de mostrar cómo la psicología evolucionaria, centrada en los mecanismos evolucionados de procesamiento de información presentes en la mente humana, proporcionaría la conexión causal necesaria entre la biología evolucionaria y los complejos e irreductibles fenómenos sociales y culturales estudiados por sociólogos, economistas, antropólogos e historiadores.

Las defensas morales del mercado

El mercado, como cualquier otro sistema de organización de la vida colectiva, es susceptible de evaluación moral. En las páginas que siguen se examinan las dos vías de fundamentación más comunes y se muestran sus limitaciones. La primera presenta al mercado como un sistema social necesario. Lo cual se puede hacer por dos caminos: a) mostrando su superioridad desde cualquier criterio de evaluación, su superioridad incondicional; b) mostrando su carácter necesario, esto es, desprovisto de moralidad. La segunda vía pretende que el mercado es el único sistema compatible con valores morales generalmente aceptados.

Intrathecal drug delivery systems for cancer pain

Introduction: A substantial number of patients with cancer suffer considerable pain at some point during their disease, and approximately 25% of cancer patients die in pain. In cases of uncontrolled pain or intolerable side effects, intrathecal drug delivery system (IDDS) is a recognised management option. Indeed, IDDS offer rapid and effective pain relief with less drug side effects compared to oral or parenteral administration. The aim of this study is to retrospectively review our series of cancer patients treated with IDDS. Method: Data was extracted from the institutional neuromodulation registry. Patients with cancer pain treated with IDDS from 01.01.1997 to 30.12.2009 were analysed for subjective improvement, changes in pain intensity (VAS) and survival time after implantation. Measurements were available for a decreasing number of patients as time since baseline increased. Results: During the studied period, 78 patients were implanted with IDDS for cancer pain. The mean survival time was 11.1 months (median: 3.8 months) and 14 patients (18%) were still alive at the end of the studied period. Subjective improvement was graded between 55 and 83% during the first year. Mean VAS during the first year remained lower than VAS at baseline. Discussion: IDDS has been shown to be cost-effective in several studies. Although initial costs of implantation are high, the cost benefits favour analgesia with implanted intrathecal pumps over epidural external systems after 3 to 6 months in cancer patients. Improved survival has been associated with IDDS and in this series both the mean and median survival times were above the cut-off value of three months. The mean subjective improvement was above 50% during the whole first year, suggesting a good efficacy of the treatment, a finding that is consistent with the results from other groups. Changes in pain intensity are difficult to interpret in the context of rapidly progressive disease such as in terminal cancer. However, mean VAS from 1 thru12 months were lower than baseline, suggesting improved pain control with IDDS, or at least a stabilisation of the pain symptoms. Conclusion: Our retrospective series suggests IDDS is effective in intractable cancer pain and we believe it should be considered even in terminally ill patients with limited life expectancies.

Canakinumab vs triamcinolone acetonide for treatment of acute flares and prevention of recurrent flares in "difficult to treat" gouty arthritis

Monosodium urate crystal deposition seen in gout stimulates IL-1 beta OR IL-1_; release. Canakinumab, a long-acting, fully human anti- IL-1 beta OR IL-1_; monoclonal antibody, effectively neutralizes IL-1 beta OR IL-1_;. Methods: This was an 8-week, dose-ranging, multi-center, blinded, doubledummy, active-controlled trial. Patients (aged 18-80 years) with an acute gout flare, refractory to or contraindicated to NSAlDs and/or colchicine, were randomized to one dose of canakinumab 10, 25, 50, 90, 150 mg s.c. or triamcinolone acetonide (TA) 40 mg i.m. Primary variable was assessed as pain intensity at 72 h post-dose (0-100 mm VAS). Secondary variables included pain intensity 24 and 48 h post-dose, time to 50% reduction in pain intensity, time to recurrence of gout flares up to 8 weeks post-dose, and rescue medication use. Results: 191/200 enrolled patients (canakinumab, n_143; TA, n_57) completed the study. Canakinumab showed significant dose-dependent pain reduction at 72 h. Canakinumab 150 mg showed superior pain relief versus TA starting from 24 h: estimated mean difference in pain intensity on VAS was -11.5 (24 h), -18.2 (48 h), and -19.2 (72 h) (all p_0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg versus 2 days with TA (p_0.0006). At Week 8, recurrent flares occurred in 1 patient (3.7%) on canakinumab 150 mg versus 25 (44.6%) patients on TA (relative risk reduction, 94%; p_0.006). During 7 days post-dose, 6 patients (22.2%) on canakinumab 150 mg, and 31 patients (55.4%) on TA, took rescue medication. Time to first rescue medication was significantly longer with canakinumab 150 mg versus TA (hazard ratio, 0.36; p_0.02). Serious adverse events (canakinumab _lsqb_n_4_rsqb_ and TA _lsqb_n_1_rsqb_) were considered not treatment-related by investigators and no patient discontinued due to adverse events. Conclusions: Canakinumab 150 mg was well-tolerated, provided rapid and sustained pain relief in patients with acute gout flares, and significantly reduced the recurrent flare risk by 94% at 8-weeks post-dose compared with triamcinolone acetonide.

Canakinumab (ACZ885) vs triamcinolone acetonide for treatment of acute flares and prevention of recurrent flares in gouty arthritis patients refractory to or contraindicated to nsaids and/or colchicine.

Purpose: Current treatments for arthritis flares in gout (gouty arthritis) are not effective in all patients and may be contraindicated in many due to underlying comorbidities. Urate crystals activate the NALP 3 inflammasome which stimulate production of IL-1β, driving inflammatory processes. Targeted IL-1β blockade may be an alternative treatment for gouty arthritis. Canakinumab (ACZ885) is a fully human monoclonal anti- IL-1β antibody with a long half-life (28 days). Method: This was an 8-weeks, dose-ranging, multicenter, blinded, double-dummy, active-controlled trial of patients ≥18 to ≤80 y with an acute gouty arthritis flare, refractory to or contraindicated to NSAIDs and/or colchicine. Patients were randomized to 1 subcutanous (sc) dose of canakinumab (10, 25, 50, 90, or 150 mg) or 1 intra muscular (im) dose of triamcinolone acetonide (TA) [40 mg]. The primary variable was assessed 72 h post-dose, measured on a 0-100 mm VAS pain scale. Secondary variables included pain intensity 24 and 48 h post dose, time to 50% reduction in pain intensity, and time to recurrence of gout flares up to 8 weeks post dose. Results: 200 patients were enrolled (canakinumab n=143, TA n=57) and 191 completed the study. A statistically significant dose response was observed at 72 h. The 150 mg dose reached superior pain relief compared to TA starting from 24h: estimated mean difference in pain intensity on 0-100 mm VAS was -11.5 at 24 h, -18.2 at 48 h, and -19.2 at 72 h (all p<0.05). Canakinumab 150 mg provided a rapid onset of pain relief: median time to 50% reduction in pain was reached at 1 day with canakinumab 150 mg vs 2 days for the TA group (p=0.0006). The probability of recurrent gout flares was 3.7% with canakinumab 150 mg vs. 45.4% with TA 8 weeks post treatment, a relative risk reduction of 94% (p=0.006). Serious AEs occurred in 2 patients receiving canakinumab (appendicitis and carotid artery stenosis) and 1 receiving TA (cerebrovascular disorder). Investigator's reported these events as not study drug related. There were no discontinuations due to AEs. Conclusion: Canakinumab 150 mg provided faster onset and superior pain relief compared to TA for acute flares in gouty arthritis patients refractory to or contraindicated to standard treatments. The 150 mg dose of canakinumab prevented recurrence of gout flares with a relative risk reduction compared to TA of 94% at 8 weeks post-dose, and was well tolerated.

Outcome of long-axis percutaneous sacroplasty for the treatment of sacral insufficiency fractures.

Our aim was to assess the clinical outcome of patients who were subjected to long-axis sacroplasty for the treatment of sacral insufficiency fractures. Nineteen patients with unilateral (n = 3) or bilateral (n = 16) sacral fractures were involved. Under local anaesthesia, each patient was subjected to CT-guided sacroplasty using the long-axis approach through a single entry point. An average of 6 ml of polymethylmethacrylate (PMMA) was delivered along the path of each sacral fracture. For each individual patient, the Visual Analogue pain Scale (VAS) before sacroplasty and at 1, 4, 24 and 48 weeks after the procedure was obtained. Furthermore, the use of analgesics (narcotic/non-narcotic) along with the evolution of post-interventional patient mobility before and after sacroplasty was also recorded. The mean pre-procedure VAS was 8 +/- 1.9 (range, 2 to 10). This rapidly and significantly (P < 0.001) declined in the first week after the procedure (mean 4 +/- 1.4; range, 1 to 7) followed by a gradual and significant (P < 0.001) decrease along the rest of the follow-up period at 4 weeks (mean 3 +/- 1.1; range, 1 to 5), 24 weeks (mean 2.2 +/- 1.1; range, 1 to 5) and 48 weeks (mean 1.6 +/- 1.1; range, 1 to 5). Eleven (58%) patients were under narcotic analgesia before sacroplasty, whereas 8 (42%) patients were using non-narcotics. Corresponding values after the procedure were 2/19 (10%; narcotic, one of them was on reserve) and 10/19 (53%; non-narcotic). The remaining 7 (37%) patients did not address post-procedure analgesic use. The evolution of post-interventional mobility was favourable in the study group as they revealed a significant improvement in their mobility point scale (P < 0.001). Long-axis percutaneous sacroplasty is a suitable, minimally invasive treatment option for patients who present with sacral insufficiency fractures. More studies with larger patient numbers are needed to explore any unrecognised limitations of this therapeutic approach.

L'assessorament educatiu en la cruïlla de la formació del professorat

El asesoramiento educativo ha sido objeto de gran atención pero a menudo es concebido como una cuestión metodológica basada en modelos que van desde la transmisión estricta de conocimientos a la colaboración entre iguales. El asesoramiento no sólo es una cuestión de sólidos procedimientos sino que también ha de atender el bienestar de las personas. Para ello es importante poder tomar en consideración los procesos de recuperación de los temas como la integración curricular o las identidades y culturas docentes. Además, la mirada de la autora se detiene en el espacio demarcado por la relación entre la escuela y quienes trabajan en ella. Una escuela que necesita abrirse al entorno y que abra vías reales de participación a la comunidad. Desde este lugar la autora expone las dificultades que atraviesa el asesoramiento en las escuelas ligadas a la necesidad de actualizar el sentido del currículum. Así el poder dar sentido a lo que hacemos y a la revisión de nuestros propósitos no es un atributo que llega mágicamente del exterior sino que resulta de un largo entramado de intercambios de opiniones que nos permiten jugar entre lo nuevo y lo viejo, lo conocido y lo desconocido, lo deseable y lo posible, etc. El asesoramiento no surge, pues, de la transmisión sino de la implicación, y constituye una de las tareas más relevantes de la formación del profesorado.

Elementos para una pedagogía de la conciencia

Este artículo parte de la necesidad cada vez más evidente de que los pedagogos emprendan una reflexión sobre el papel de la conciencia en la educación del hombre. Para ello se revisan, en primer lugar, algunas de las críticas clásicas a la conciencia y a lo mental y se ve que es imposible concluir resultados absolutamente ciertos. En consecuencia, se parte de un programa de trabajo que le supone a la conciencia existencia autónoma, propositividad y fuerza causal. Posteriormente se analizan los mecanismos mentales, distinguiéndose los procesos de representación, modificación y construcción del yo autoconsciente. Se concluye proponiendo la autorregulación consciente y el dominio del yo como una de las posibles vías de la pedagogía de la conciencia.

El fundamento de la metodología comparativa en educación

Lo que se pretende en este estudio es establecer el fundamento de la metodología comparativa en educación. Se logra presentando un conjunto de doce características que constituyen un amplio sistema de relaciones e interrelaciones que definen la metodología comparativa. La idea dominante es que para establecer una comparación entre dos hechos o fenómenos es preciso que tengan algo en común, y deben ser vistos así por la aplicación de . un criterio comparativo que permita ordenar y relacionar las diferentes variables objeto de estudio. La comparación tiene por objeto descubrir las semejanzas, las diferencias y las diversas relaciones que pueden establecerse. Comparar es pensar relacionando. Se insiste en la importancia de las coordenadas espacio y tiempo en la comparación, pues ésta supone una afinidad o proximidad geográfica e histórica. La comparación suele tender hacia una unificación o generalización. Se parte de un estado de desigualdad o diferencia entre dos o más realidades, pero se acaba por descubrir entre ellas algún principio de unidad, alguna ley común. Incluso en la práctica, la Pedagogía Comparada expresa a menudo su deseo de servir al ideal de unidad entre los diferentes pueblos, a través de una unidad establecida en sus sistemas educacionales. Con los pronósticos educacionales que intenta ayudar a formar, quiere dar una base a las políticas educativas para que funcionen lo más correctamente posible. Al enumerar las etapas del análisis comparativo se reproduce el esquema de F. Hilker y G. Bereday, por considerar lo ya clásico en Pedagogía Comparada. En el comentario de cada una de las cuatro fases se explica ampliamente en qué consisten éstas y se,señalan modalidades originales de aplicación de las mismas Se insiste en que el método comparativo no debe limitarse a los llamados estudios de área (o sistemas educativos nacionales y regionales), sino que debe aplicarse también a otros sectores pedagógicos. Finalmente se señalan unas vías que pueden ayudar a un avance de la Pedagogía Comparada, aun reconociendo las limitaciones propias de ésta, que es calificada como una disciplina más esclarecedora y orientadora que normativa.

Physical activity and energy expenditure in rheumatoid arthritis patients and matched controls.

OBJECTIVES: To compare daily energy expenditure between RA patients and matched controls, and to explore the relationship between daily energy expenditure or sedentariness and disease-related scores. METHODS: One hundred and ten patients with RA and 440 age- and sex-matched controls were included in this study. Energy expenditure was assessed using the validated physical activity (PA) frequency questionnaire. Disease-related scores included disease activity (DAS-28), functional status (HAQ), pain visual analogue scale (VAS) and fatigue VAS. Total energy expenditure (TEE) and the amount of energy spent in low- (TEE-low), moderate- (TEE-mod) and high-intensity (TEE-high) PAs were calculated. Sedentariness was defined as expending <10% of TEE in TEE-mod or TEE-high activities. Between-group comparisons were computed using conditional logistic regression. The effect of disease-related scores on TEE was investigated using linear regression. RESULTS: TEE was significantly lower for RA patients compared with controls [2392 kcal/day (95% CI 2295, 2490) and 2494  kcal/day (2446, 2543), respectively, P = 0.003]. A significant difference was found between groups in TEE-mod (P = 0.015), but not TEE-low (P = 0.242) and TEE-high (P = 0.146). All disease-related scores were significantly poorer in sedentary compared with active patients. TEE was inversely associated with age (P < 0.001), DAS-28 (P = 0.032) and fatigue VAS (P = 0.029), but not with HAQ and pain VAS. CONCLUSION: Daily energy expenditure is significantly lower in RA patients compared with matched controls, mainly due to less moderate-intensity PAs performed. Disease activity and fatigue are important contributing factors. These points need to be addressed if promoting PA in RA patients is a health goal. Trial registration. ClinicalTrials.gov, http://clinicaltrials.gov, NCT01228812.

Protección tecnológica y contractual de las obras con derecho de autor: ¿Hacia una privatización del acceso a la información?

Los problemas que el gran desarrollo de la información digital e Internet están provocando al derecho de autor se están intentando solucionar a través de tres vías: legislativa, tecnológica y contractual. La protección proporcionada a las obras con derecho de autor mediante medidas tecnológicas complementa a las condiciones de uso establecidas en las licencias y, además, ambos tipos de protección están respaldados por las nuevas leyes surgidas para adaptarse al nuevo contexto tecnológico. Como resultado de esta triple protección se están poniendo en grave peligro las excepciones y limitaciones a los derechos de autor reconocidas por las leyes de derecho de autor para beneficiar a las bibliotecas, sus usuarios y los ciudadanos en general, dando lugar a una fuerte y peligrosa privatización del acceso a la información.