ABSTRACT
Objetivos: Hace más de diez años que salieron al mercado los últimos fármacos con indicación en las guías internacionales de dolor neuropático (DN). Estas recomiendan iniciar con monoterapia y sitúan el tratamiento combinado en el segundo escalón. Un considerable número de pacientes no alcanza un suficiente alivio del dolor o mejora de su calidad de vida con los fármacos disponibles. Bajo esta perspectiva, el Grupo de Trabajo (GT) de DN de la Sociedad Española del Dolor (SED) diseñó una encuesta para el abordaje del DN mediante fármacos, técnicas intervencionistas y tratamientos fuera de indicación en nuestro medio. En este artículo se analiza solo la parte de tratamientos farmacológicos. Material y métodos: Estudio descriptivo mediante un cuestionario autoadministrado difundido por correo electrónico a los socios de la SED en dos oleadas durante 2019. Al inicio del cuestionario se realizaba una pregunta de selección sobre si utilizaban o no tratamientos fuera de ficha técnica o fuera de indicación. Solo los que respondieron afirmativamente procedieron a todo el conjunto de preguntas. Este se dividió en los siguientes bloques: antiepilépticos, antidepresivos, antipsicóticos, anestésicos, anti-nmda, cannabinoides, naltrexona, tratamientos tópicos, toxina botulínica, polifarmacia y tratamientos fuera de ficha. Dentro de la sección de tratamientos tópicos se incluyó la toxina botulínica. Resultados: La tasa de respuesta fue del 13,82 %, siendo del 10,05 % una vez descartadas las no válidas. El 21 % comienzan el tratamiento del DN con polifarmacia y un 43 % lo hace cuando no responden a una primera línea. El 40 % de los encuestados opinan que no hay evidencia suficiente para el uso de polifarmacia. El 70 % de los participantes trataban hasta un 30 % de sus pacientes con DN con fármacos fuera de indicación. El 23,3 % utilizaban medicamentos fuera de ficha técnica entre el 40 % y el 60 % de los pacientes con DN y un 6,6 % lo hacía en un 70-90 %...(AU)
Objectives: Latest drugs with an indication for neuropathic pain (NP) in the international guidelines came onto the market more than ten years ago. They recommend starting with monotherapy and place the combined treatment in the second step. A considerable number of patients do not achieve sufficient pain relief or improvement in their quality of life with the available drugs. From this perspective, the NP Working Group (WG) of the Spanish Pain Society (SED) designed a survey to address how NP drugs, off-label treatments and interventional techniques are being used in our setting. In this article we will only discuss the pharmacological treatment options.Material and methods: Descriptive study using a self-administered questionnaire distributed by email to SED members in two waves during 2019. At the beginning of the questionnaire, a selection question was asked whether or not they used non-technical or off-label treatments. Only those who answered affirmatively proceeded to the entire set of questions. It was divided into the following blocks: antiepileptics, antidepressants, antipsychotics, anesthetics, anti-nmda, cannabinoids, naltrexone, topical treatments, botulinum toxin, polypharmacy and off-label treatments. Botulinum toxin was included in the topical treatments section. Results: The response rate was 13.82 %, being 10.05 % once the invalid ones had been ruled out. 21 % begin the treatment of NP directly on polypharmacy and 43 % do so when they do not respond to a first line. 40 % of those surveyed think that there is insufficient evidence for the use of polypharmacy. 70 % of the participants treated up to 30 % of their NP patients with off-label drugs. 23.3 % used off-label medications in between 40 % and 60 % of patients with NP and 6.6 % did so in 70-90 % of patients...(AU)
Subject(s)
Humans , Chronic Pain/classification , Pain Management , Diabetic Neuropathies/drug therapy , Quality of Life , Drug Therapy , Epidemiology, Descriptive , Surveys and Questionnaires , Spain , Chronic Pain/drug therapy , Chronic Pain/therapyABSTRACT
PURPOSE: To correlate tear fluorescein clearance with interleukin-1alpha (IL-1alpha) concentration and gelatinase B (matrix metalloproteinase [MMP]-9) activity in the tear fluid of patients with ocular rosacea and normal control subjects. METHODS: Gelatinase activity was evaluated by gelatin zymography in tear fluid obtained from 13 patients with ocular rosacea (including 1 patient with recurrent epithelial erosion, 2 with recurrent peripheral corneal infiltrates and vascularization, and 2 patients with epithelial basement membrane dystrophy) and 13 normal subjects with normal aqueous tear production and no irritation symptoms. Tear fluorescein clearance was evaluated by measuring fluorescence in tear fluid collected from the inferior meniscus 15 minutes after instillation of 5 microl of 2% Na-fluorescein with a CytoFluor II fluorometer. Pro-MMP-9 and IL-1alpha concentrations in the tear fluid were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with normal control subjects, patients with ocular rosacea had a greater delay of tear fluorescein clearance (P < 0.001), a higher tear IL-1alpha concentration (P < 0.001), and a greater pro-gelatinase B (92 kDa) activity (P < 0.001) in their tear fluid. The 84-kDa active form of gelatinase B was observed in 46% of the rosacea tear samples and none of the controls. The zymographic results were confirmed by ELISA that showed a significantly greater concentration of pro-MMP-9 (92 kDa) in the tear fluid of rosacea patients than controls. Delayed tear clearance was correlated with elevated tear IL-1alpha concentration (p=0.67, P < 0.001) and increased tear gelatinase B activity (p=0.84, P < 0.001). Tear IL-1alpha concentration was correlated with tear gelatinase B activity (p=0.58, P < 0.002). CONCLUSIONS: Gelatinase B (MMP-9) activity is greater in patients with ocular rosacea than in normal eyes. The majority of this activity is due to 92-kDa proform of this enzyme. This activity is correlated with delayed tear clearance and tear fluid concentration of interleukin-1alpha, a proinflammatory cytokine that has been reported to stimulate gelatinase B production. Elevated gelatinase B activity in ocular rosacea may be involved in the pathogenesis of the irritation symptoms, recurrent epithelial erosions, vascularization, and epithelial basement membrane dystrophy that develops in the corneas of patients with this condition.
Subject(s)
Collagenases/metabolism , Conjunctival Diseases/metabolism , Corneal Diseases/metabolism , Fluorescein/pharmacokinetics , Interleukin-8/metabolism , Rosacea/metabolism , Tears/enzymology , Adult , Aged , Aged, 80 and over , Enzyme-Linked Immunosorbent Assay , Female , Fluorophotometry , Humans , Male , Matrix Metalloproteinase 9 , Middle AgedABSTRACT
OBJECTIVE: To correlate and compare the Schirmer 1 test and a new method of measuring tear fluorescein clearance with the CytoFluor II fluorometer with the severity of ocular irritation symptoms, clinical signs of meibomian gland disease, corneal fluorescein staining scores, and corneal and conjunctival sensitivity. DESIGN: Case-control study. PARTICIPANTS: Forty patients presenting with a chief complaint of ocular irritation, and 40 asymptomatic control subjects of similar age distribution. INTERVENTION: All subjects completed a symptom questionnaire, a baseline ocular examination, fluorescein clearance test (FCT), and Schirmer 1 test. MAIN OUTCOME MEASURES: The FCT was performed with a CytoFluor II fluorophotometer by measuring the fluorescein concentration in minimally stimulated tear samples collected from the inferior tear meniscus 15 minutes after instillation of 5 microl of 2% sodium fluorescein. Severity of ocular irritation was assessed with a symptom questionnaire. Schirmer 1 test, biomicroscopic meibomian gland evaluation, corneal fluorescein staining score, and corneal and conjunctival sensation scores were assessed with the Cachet-Bonnet anesthesiometer in all subjects. RESULTS: Irritation symptoms correlated with higher log tear fluorescein concentration (symptomatic 3.08 +/- 0.62 units/,microl, normal control 1.89 +/- 0.7 units/microl, P < 0.005) and lower Schirmer 1 test scores (symptomatic 12.6 mm, normal control 22.3 mm, P < 0.005). The FCT showed greater predictive value for identifying ocular irritation than the Schirmer 1 test. A fluorescein concentration of 274 units//microl eliminated 80% of the normal subjects (specificity) and identified 85% of the abnormal subjects (sensitivity). Log of tear fluorescein concentration and the Schirmer 1 test correlated with meibomian gland orifice metaplasia (2.81 +/- 0.78 units/microl and 14.47 +/- 9.53 mm in those with metaplasia vs. 1.83 +/- 0.71 units/microl and 23.14 +/- 7.67 mm in those without metaplasia, P < 0.001) and with the percentage of acinar dropout. Both log of tear fluorescein concentration and the Schirmer 1 test correlated with corneal fluorescein staining (Pearson correlation of 0.394 P < 0.0001 for Schirmer 1 test and 0.312 P < 0.005 for log of tear fluorescein). In addition, log of tear fluorescein and Schirmer 1 test scores correlated with corneal and conjunctival sensation scores (Spearman's rho for corneal sensation: log of tear fluorescein -0.38, P < 0.003, Schirmer 1 test -0.39, P < 0.002, and for conjunctival sensation: log of tear fluorescein -0.391, P < 0.001, Schirmer 1 test -0.23, P < 0.061). CONCLUSIONS: The FCT shows a greater predictive value for ocular irritation than the Schirmer 1 test. It correlates better with age, meibomian gland dysfunction, and decreased corneal and conjunctival sensation. Decreased tear clearance was identified as a risk factor for ocular irritation, even in subjects with normal Schirmer scores. This simple technique may provide new clues into the mechanism and therapy of ocular irritation.
