ABSTRACT Introduction: Breakthrough pain (BTP) is a common health problem, badly known and poorly treated in spite of the advancement in its treatment. Guidelines have been published recently by Scientific Societies involved in their management in order to improve the diagnosis and treatment. Objectives: To know the degree of knowledge and professional agreement with Scientific Societies recommendations, the auto perception in the follow-up and the real follow-up by doctors in their outpatient clinics. Materials and methods: A descriptive study from professionals' opinions that were recorded in an electronic survey at two sequential times. A self-audit of clinical habits was performed between them. Professionals evaluated the level of agreement and the application of 12 recommendations from the guidelines in five patients with BPT in their outpatient clinics. Results: A total of 202 doctors from breakthrough pain units and palliative care participated in the study, at a national level; the mean of professional experience was 11.9 years. Mean age was 47.9 years and 45 % were women. Recommendations' document was known by 86.6 %. Recommendations with lower degree of agreement or considered less followed-up by professionals were: 1. Recommendation related to the patient's follow-up during medication titration process: 78.7 % and 18.3 % of surveyed were totally or partially agree with it while 59.4 % always applied it. 2. Recommendation related to prevention of opioid side effects from the beginning of the treatment: 56.4 % and 18.8 % of surveyed were totally or partially agree with it while 66.3 % always applied it. 3. Recommendation related to the need of the patient of receiving opioids for baseline pain: 76.7 % and 35.6 % of surveyed were totally or partially agree with it while 66.8 % always applied it. After clinical records self-audit, recommendations regarding patients' follow-up and prevention of side effects were not applied between 15 and 20 % of the times, in line to previous perceptions from specialists. However, recommendation related to the use of opioids for baseline pain disclosed a lower breach (7 %) than perceived (33.2 %). Conclusions: Professionals from Pain Units and Palliative Care Units have a realistic and accurate perception of the quality of their job in patients with breakthrough pain as well as the improvement areas in their daily job regarding the follow-up and application of recommendations based in scientific evidence.

RESUMEN Introducción: El dolor irruptivo oncológico (DIO) es un problema de salud frecuente, mal conocido e incorrectamente tratado a pesar de los avances en su tratamiento. Las sociedades científicas implicadas en su manejo han publicado recientemente recomendaciones para la optimización de su diagnóstico y tratamiento. Objetivos: Conocer el grado de conocimiento y de acuerdo de los profesionales con las recomendaciones de las sociedades científicas, la autopercepción del seguimiento de las mismas por los médicos y su seguimiento real en la clínica. Material y métodos: Estudio descriptivo de las opiniones de los profesionales recogidas en un cuestionario electrónico en dos momentos secuenciales entre los que intermedió una autovaloración (self-audit) de hábitos clínicos. Los profesionales evaluaron el grado de acuerdo y la aplicación de 12 recomendaciones de las guías en cinco pacientes con DIO en seguimiento en consulta. Resultados: En el estudio participaron 202 médicos de unidades del dolor y cuidados paliativos de ámbito nacional con una media de 11,9 años de experiencia laboral. La edad media fue 47,9 años y el 45 % fueron mujeres. El 86,6 % conocía el documento de recomendaciones. Las recomendaciones que alcanzaban menor grado de acuerdo o se percibían como menos aplicadas por los profesionales fueron: 1. La recomendación relacionada con el seguimiento del paciente durante la titulación del tratamiento: el 78,7 % y el 18,3 % de los encuestados mostraron un acuerdo pleno o parcial con la misma y el 59,4 % la aplicaba casi siempre. 2. La recomendación sobre la prevención de efectos secundarios del tratamiento con opioides desde el inicio: el 76,7 % y el 18,8 % mostraron acuerdo pleno o parcial, el 66,3 % la aplicaba casi siempre. 3. La recomendación sobre la necesidad de que el paciente esté recibiendo opioides para el tratamiento del dolor basal: el 56,4 % y el 35,6 % mostraron acuerdo pleno o parcial, el 66,8 % la aplicaba casi siempre. Tras el self-audit de historias clínicas, las recomendaciones sobre el seguimiento de los pacientes y la prevención de efectos secundarios no se aplicaban en el 15 y 20 % de las ocasiones, en línea con las percepciones previas de los especialistas. Sin embargo, la recomendación sobre la utilización previa de opioides para el dolor basal reveló un incumplimiento menor (7 %) al percibido (33,2 %). Conclusiones: Los profesionales de Unidades del Dolor y de Unidades de Cuidados Paliativos tienen una percepción realista y precisa de la calidad de su trabajo en los pacientes con dolor irruptivo, así como de los aspectos mejorables de su práctica clínica diaria en relación con el seguimiento y la aplicación de las recomendaciones basadas en la evidencia científica.

Aim and objective: This study was intended to avaluate the efficacy and tolerability of pregabalin in patients with neuropathic pain and concomitant medication. Material and methods: Investigator-initiated, prospective multicenter study, open-label, uncontrolled conducted in 10 pain units from Catalonia hospitals. Pregabalin was consecutively prescribed at the physicians' discretion to avoid selective bias. Inclusion criteria were: outpatient, age >18 years, admission diagnosis as "neuropathic pain" and informed consent. Exclusion criteria were pregnancy or cognitive disorders. Protocol scheduled five study visits: at baseline, 15 days, 1 month, 2 months, and 3 months of treatment. Titration of pregabalin doses was pre-specified. We recorded: age, sex, type of neuropathic pain (pure or mixed), VAS (baseline, 15 days, 1 month, 2 and 3 months), MOS sleep scale (baseline and third month), concomitant drug treatment and adverse effects episodes. Patients were divided into three groups: pregabalin + NSAID + tricyclic antidepressants (NSAID+TCA), pregabalin + NSAID + anxiolytics (NSAID+ANX), pregabalin + NSAID + opioids (NSAID+OPI). A parametric Student's t test and non-parametric Wilcoxon test for paired data of quantitative variables were performed. Results: 578 patients were recruited and 472 (81.66%) completed the study. 98.8% of patients were treated with politherapy. Pain relief: mean reduction by -3.6 (± 1.9) (p < 0.0001) points. By type of pain: mixed pain -3.7 (± 1.7) (p < 0.0001); pure neuropathic pain -3.4 (± 2.2) (p < 0.0001). By adjuvant medication, the NSAID + TCA group -3.1 (± 1.9) (p = 0.0002); NSAID + ANX -3.4 (± 2.0) (p < 0.0001); NSAID + OPI -3.7 (± 1.9) (p < 0.0001). Sleep improvement: mean reduction by -1.9 (± 6.4) (p < 0.0001) points. By type of pain: mixed pain -3.1 (± 7.0) (p < 0.0001); pure neuropathic pain -1.1 (± 4.2) (p < 0.0001). By adjuvant medication, NSAID+OPI -2.1 (± 6.0) (p < 0.0001); NSAID + TCA and NSAID + ANX groups both -1.0 not statistically significant (p = 0.1250 and p = 0.4063 respectively). 90 patients (15.6%) discontinued the study due to adverse effects. Conclusions: Treatment with pregabalin induces a fast and significant relief of neuropathic pain, improves sleep and shows a low drug interaction profile.

Introducción: Se pretendió evaluar la eficacia y tolerabilidad de la pregabalina, para el tratamiento del dolor neuropático en las Unidades de Dolor hospitalarias. Material y método: Estudio prospectivo, multicéntrico, abierto, que se llevó a cabo en 10 unidades del dolor de hospitales de Cataluña. Se prescribió pregabalina, a criterio del facultativo, de manera consecutiva. Criterios de inclusión: consentimiento, dolor neuropático, mayor de edad y paciente externo. Criterios de exclusión: alteraciones cognitivas, embarazo. Se estipularon 5 visitas: basal, 15 días, 1 mes, 2 y 3 meses de tratamiento. La titulación de las dosis de pregabalina estaba preespecificada. Se registró edad, sexo, tipo de dolor neuropático, EVA (basal, 15 días, 1 mes, 2 meses, 3 meses), escala MOS de sueño (basal y tercer mes), tratamiento farmacológico concomitante y episodios de efectos adversos. Se crearon 3 grupos de estudio: pregabalina + antiinflamatorios no esteroideos (AINE) + antidepresivos tricíclicos (AINE + ATC), pregabalina + AINE + ansiolíticos (AINE + ANS), pregabalina + AINE + opioides (AINE + OPI). Se efectuó prueba paramétrica t de Student y test no paramétrico de Wilcoxon para datos apareados de variables cuantitativas. Resultados: Se reclutaron 578 pacientes de los que 472 (81,66%) completaron el estudio. El 98,8% recibieron politerapia. El alivio del dolor registró una media de -3,6 (± 1,9) (p < 0,0001) puntos. Por tipo de dolor: mixto -3,7 (±1,7) (p < 0,0001); puro -3,4 (± 2,2) (p < 0,0001). Por medicación coadyuvante: grupo AINE + ATC -3,1 (± 1,9) (p = 0,0002); AINE + ANS -3,4 (± 2,0) (p < 0,0001); AINE + OPI -3,7 (± 1,9) (p < 0,0001). Mejora del sueño: media de -1,9 (± 6,4) (p < 0,0001) puntos. Por tipología: mixto -3,1 (± 7,0) (p < 0,0001); puro -1,1 (± 4,2) (p < 0,0001). Por medicación coadyuvante: grupo AINE + OPI -2,1 (± 6,0) (p < 0,0001); AINE + ATC y AINE + ANS ambos -1,0 no estadísticamente significativo, (p = 0,1250 y p = 0,4063 respectivamente). 90 pacientes (15,6%) discontinuaron el estudio debido a efectos adversos. Conclusiones: La pregabalina produjo una reducción rápida y significativa del dolor neuropático, una relevante mejoría del sueño, demostrando un perfil bajo de interacción y buena tolerancia.

The objective of the present study was to explore the regulatory mechanisms of free radicals during streptozotocin (STZ)-induced pancreatic damage, which may involve nitric oxide (NO) production as a modulator of cellular oxidative stress. Removal of oxygen species by incubating pancreatic tissues in the presence of polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) (1 U/ml) produced a decrease in nitrite levels (42%) and NO synthase (NOS) activity (50%) in diabetic but not in control samples. When NO production was blocked by N G-monomethyl-L-arginine (L-NMMA) (600 µM), SOD activity increased (15.21 ± 1.23 vs 24.40 ± 2.01 U/mg dry weight). The increase was abolished when the NO donor, spermine nonoate, was added to the incubating medium (13.2 ± 1.32). Lipid peroxidation was lower in diabetic tissues when PEG-SOD was added (0.40 ± 0.02 vs 0.20 ± 0.03 nmol/mg protein), and when L-NMMA blocked NOS activity in the incubating medium (0.28 ± 0.05); spermine nonoate (100 µM) abolished the decrease in lipoperoxide level (0.70 ± 0.02). We conclude that removal of oxygen species produces a decrease in pancreatic NO and NOS levels in STZ-treated rats. Moreover, inhibition of NOS activity produces an increase in SOD activity and a decrease in lipoperoxidation in diabetic pancreatic tissues. Oxidative stress and NO pathway are related and seem to modulate each other in acute STZ-induced diabetic pancreas in the rat.