[Key guidelines on the Spanish multi-society consensus on chronic kidney disease]. / Consideraciones sobre el consenso español multisociedad de manejo de la enfermedad renal crónica.

Chronic kidney disease (CKD) is a global health problem and affects approximately 15.1% of the general population in Spain (IBERICAN and ENRCA studies), although most of the literature agrees that there is an underdiagnosis that would further increase this prevalence. This article from the CKD monograph aims to summarize the main consensus guidelines for the management of CKD, highlighting the most important and novel aspects, as well as recently updated terminology and concepts. Sections addressing specific populations and prevention strategies are also included. As the family doctor (MAP) plays a fundamental role in the detection of CKD, recommendations on the multidisciplinary approach to CKD are collected.

Estado de control de pacientes en tratamiento con anticoagulantes orales antagonistas de la vitaminaK en atención primaria. Estudio ECOPAVIK / Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care

Introducción. En España, más del 80% de pacientes con fibrilación auricular (FA) reciben tratamiento anticoagulante oral (TAO), con un seguimiento dentro del ámbito de la atención primaria (AP) del 72% de los pacientes. Estudios recientes demuestran que existe un deficiente control de los pacientes con anticoagulantes orales (ACO). El objetivo de este estudio fue obtener un conocimiento más detallado del estado de control, así como de las patologías que lo indican y están en comorbilidad en los pacientes en tratamiento con ACO antagonistas de la vitaminaK (AVK). Metodología. Estudio observacional retrospectivo/transversal en el que participaron pacientes de una zona básica de salud incluidos dentro del programa TAO durante 2014. Se consideró que el control de INR en pacientes en tratamiento con ACO era inadecuado cuando el porcentaje de tiempo en rango terapéutico (TRT) era inferior al 65% durante un periodo de valoración de al menos 6meses. Resultados. Se incluyeron 368 pacientes, en los que la patología con indicación de anticoagulación oral más prevalente fue la FA no valvular. Se realizaron 5.128 controles, de los cuales 2.359 (46%) estaban fuera de rango terapéutico y 2.769 (54%) estaban en rango terapéutico. El 91% de los pacientes en tratamiento con ACO AVK presentaban un riesgo muy elevado de tromboembolismo. Conclusiones. La indicación de anticoagulación en nuestra población es correcta, asumiendo un riesgo hemorrágico bajo/intermedio en la mayoría de los pacientes. La medición del TRT mediante el método de Rosendaal indica que existe un deficiente control de los pacientes en tratamiento con ACO AVK (AU)

Background. In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. Methods. This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. Results. A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. Conclusions. The indication for anticoagulation is correct in our population, assuming a low-intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient (AU)

[Update on the control of patients on treatment with vitaminK antagonist oral anticoagulants in Primary Care]. / Estado de control de pacientes en tratamiento con anticoagulantes orales antagonistas de la vitaminaK en atención primaria. Estudio ECOPAVIK.

BACKGROUND: In Spain, more than 80% of patients with atrial fibrillation (AF) receive oral anticoagulant therapy (OAT), and 72% of these patients are followed up in the Primary Care (PC) setting. Recent studies have shown that there is insufficient control of patients on OAT. The objective of the present study was to obtain more detailed information on the state of control of patients on treatment with vitaminK antagonist (VKA) oral anticoagulants (OAC), on the diseases for which the therapy was indicated and on concomitant diseases. METHODS: This was a retrospective, cross-sectional, observational study with the participation of patients from a single health area included in an OAT programme throughout 2014. In patients on treatment with OAC, International Normalised Ratio (INR) control was considered insufficient when the percentage time in therapeutic range (TTR) was below 65% during an evaluation period of at least 6months. RESULTS: A total of 368 patients were included in the study, where the most frequent indication for oral anticoagulation was non-valvular AF. A total of 5,128 INR controls were performed, of which 2,359 (46%) were outside the therapeutic range, and 2,769 (54%) were within range. The risk of thromboembolism was very high in 91% of patients on treatment with VKA OAC. CONCLUSIONS: The indication for anticoagulation is correct in our population, assuming a low-intermediate risk of haemorrhage in the majority of patients. Measurement of the TTR using the Rosendaal method shows that the control of patients on treatment with VKA OAC is insufficient.

Lúnulas rojas en alopecia areata / Red lunulae in alopecia areata

Las lúnulas rojas pueden observarse de forma excepcional en la alopecia areata. Describimos el caso de una mujer de 23 años con alopecia areata en placas multifocal de un año de evolución que evoluciona a una alopecia areata total. Pocas semanas después, se pueden apreciar lúnulas rojas en todos los dedos de las manos y en el primer dedo de ambos pies. La patogénesis de las lúnulas rojas es incierta. Suelen desarrollarse poco después de la fase aguda y desaparecen lentamente dejando, en algunos casos, líneas de Beau (AU)

Red lunulae have been observed excepcionally in alopecia areata. We describe a 23-year-old girl with a multifocal alopecia areata of one year evolution which progress to a totalis. Few weeks later, we can observe red lunulae in all fingernails and both great to enails. Pathogenesis of red lunulae is uncertain. They usually appear shortly after the acute on set of hair loss and disappear slowly leaving, in some cases, Beau´s lines(AU)

Direct determination of closely overlapping drug mixtures of diflunisal and salicylic acid in serum by means of derivative matrix isopotential synchronous fluorescence spectrometry.

A direct method for the simultaneous fluorimetric determination of two anti-inflammatory drugs in serum is proposed. The combination of matrix isopotential synchronous fluorescence (MISF) and first derivative technique provides good analytical results and permits the simultaneous determination of diflunisal and salicylic acid in human serum. MISF spectra are obtained by calculating the isopotential trajectory in the three-dimensional fluorescence spectrum for a serum solution. In the spectral contour, the trajectory is taken to be the portion of the line that passes by the fluorescence maxima of both compounds ensuring a sensitivity level similar to that of a direct determination in absence of background fluorescence. Analysis was carried out in water using a pH of 7.2 provides by 0.1 M sodium dihydrogen phosphate buffer. Serum samples are diluted 100 times and provide linear calibration plots at diflunisal and salicylic acid concentrations up to 800 ng mL(-1). The goodness of the analytical signal was checked by using variance analysis. Signals recorded throughout the calibration range were subjected to three calibrations per each analyte, both in the absence and in the presence of variable amounts of the other analyte. Differences between individual calibrations and slopes were compared with those within individual calibrations. Based on the results, diflunisal and salicylic acid can be accurately quantified in the presence of each other. The limit of detection calculated according to Clayton who uses error propagation throughout the calibration curve and a non-centralized security factor was 36.8 and 37.3 ng mL(-1) for diflunisal and salicylic acid, respectively.

Prurito y enalapril / Pruritus and enalapril

El prurito asociado a los fármacos inhibidores de la enzima convertidora de angiotensina (IECA) es un efecto secundario poco descrito en la literatura española. Presentamos 4 pacientes afectos de prurito generalizado debido al enalapril que cedió tras la suspensión del fármaco. Es importante identificar que una de las posibles causas de prurito persistente y prolongado en algunos pacientes es este tipo de fármacos (AU)

Fast determination of propranolol in urine and pharmaceutical preparations by stopped-flow and micellar-stabilized room-temperature phosphorescence: validation of the method.

The stopped-flow mixing technique has been used to study the kinetic determination of propranolol by means of micellar-stabilized room-temperature phosphorescence. This mixing system diminishes the time required for the deoxygenation of micellar medium by sodium sulfite, allowing a kinetic curve that levels off within only 7s to be obtained. The phosphorescence enhancers thallium (I) nitrate, sodium dodecyl sulfate, and sodium sulfite were optimized to obtain maximum sensitivity and selectivity. A pH value of 6.54 was selected as adequate for phosphorescence development. The kinetic curves of propranolol phosphorescence were scanned at lambda(ex)=290 nm and lambda(em)=524 nm. The calibration graphs were linear for the concentration range from 25 to 400 ng mL(-1). The phosphorescence lifetime of propranolol is approximately 1210 micros. The detection limit calculated as proposed clayton was 13.53 ng mL(-1) and by applying the error propagation theory, the detection limit was 8.37 ng mL(-1). The repeatability was studied using 10 solutions of 200 ng mL(-1) of propranolol; if error propagation theory is assumed, the relative error is 1.94%. The standard deviation for a replicate sample was 4.0 ng mL(-1). This method was successfully applied to the determination of propranolol in commercial formulations and in urine. Suitable recovery values were obtained.

Control of propranolol intake by direct chromatographic detection of alpha-naphthoxylactic acid in urine.

A rapid chromatographic procedure with a C18 column, a mobile phase of 0.15 M sodium dodecyl sulfate (SDS)-10% (v/v) 1-propanol at pH 3 (0.01 M phosphate buffer), and fluorimetric detection, is reported for the control of propranolol (PPL) intake in urine samples, which are injected directly without any other treatment than filtration. The peak of PPL was only observed in samples taken a few hours after ingestion of the drug due to its extensive conjugation and metabolisation. The detection of several unconjugated PPL metabolites was therefore considered: desisopropylpropranolol (DIP), propranolol glycol (PPG), alpha-naphthoxylactic acid (NLT) and alpha-naphthoxyacetic acid (NAC). NLT showed the best characteristics: it eluted at a much shorter retention time than PPL, its concentration in urine samples was greater and it did not present any interference from endogeneous compounds in urine, common drugs or drugs administered in combination with PPL. The limit of quantification, measured as the concentration of analyte providing a relative standard deviation of 20%, was 24 ng/ml, and the day-to-day imprecision was below 4% for concentrations above 200 ng/ml. The procedure allows the routine control of PPL at therapeutic urine levels. Urinary excretion studies showed that the detection of NLT is possible at least up to 20-30 h after oral administration.

Stopped-flow determination of dipyridamole in pharmaceutical preparations by micellar-stabilized room temperature phosphorescence.

The stopped flow mixing technique has been used to study the kinetic determination of dipyridamole by means of micellar-stabilized room temperature phosphorescence (RTP). This mixing system diminishes the time required for the deoxygenation of the micellar medium by sodium sulfite. The phosphorescence enhancers thallium (I) nitrate, sodium dodecyl sulfate (SDS), and sodium sulfite were optimized to obtain maximum sensitivity and selectivity. A pH value of 10.6 was selected as adequate for phosphorescence development. The kinetic curve of dipyridamole phosphorescence was scanned at lambda(ex)=303 nm and lambda(em)=616 nm. Then, the intensity at 10 s, and the maximum slope of phosphorescence development, for an interval time of 1 s, were measured. Two determination approaches: intensity and rate methods, were proposed. The calibration graphs were linear for the concentration range from 50 to 400 ng ml(-1). The detection limits, according to Clayton et al., Anal. Chem. 59 (1987) 2506, were 21.5 and 37.5 ng ml(-1), for intensity and initial rate measurements, respectively. By applying the error propagation theory, the detection limits were 19.0 and 33.0 ng ml(-1), for intensity and initial rate measurements, respectively. Two commercial formulations (persantin and asasantin) were analyzed by both proposed methodologies. Adequate recovery values were obtained in both cases.

Determination of nafronyl in pharmaceutical preparations by means of stopped-flow micellar-stabilized room temperature phosphorescence.

The stopped-flow mixing technique was applied to micellar-stabilized room temperature phosphorimetry by measuring the fast appearance of the phosphorescent signal yielded by nafronyl in the presence of sodium dodecyl sulfate and thallium nitrate. This mixing system diminishes the time required for the deoxygenation of micellar medium by sodium sulfite, allowing a kinetic curve that levels off within only 5 s to be obtained. Phosphorescence enhancers thallium(I) nitrate, sodium dodecyl sulfate and sodium sulfite were optimized to obtain maximum sensitivity and selectivity. A pH value of 10.5 was selected as adequate for phosphorescence development. Two rapid, straightforward and automatic methods were proposed using the slope and amplitude of the kinetic curve, which are directly proportional to the nafronyl concentration, as analytical parameters. Calibration graphs were linear for the concentration range from 30 to 600 ng ml-1. Praxilene, the only commercial formulation containing nafronyl, was analysed by both proposed methodologies. Suitable recovery values were obtained.

Direct determination of amiloride in urine using isopotential fluorimetry.

A method for the determination of amiloride at concentrations between 15 and 152 ng ml-1 by means of matrix isopotential synchronous fluorescence spectrometry and derivative techniques is proposed. This method is useful for the determination of compounds in samples with unknown background fluorescence without the need for tedious pre-separation. As amiloride is widely used as a doping substance in sport, the method was successfully applied to the determination of amiloride in urine. To obtain maximum sensitivity and adequate selectivity, factors affecting fluorescence intensity were studied in the amiloride band centered and lambda ex = 362 nm and lambda em = 415 nm. As a result, the determination was performed in an ethanol-water (1 + 1, v/v) medium at pH 6.3, adjusted by using sodium citrate-citric acid (0.1 M) as buffer solution. The concentration of amiloride in urine samples can be calculated by recording its total luminescence spectrum and applying the isopotential trajectory of the urine that cuts the selected band of amiloride. The unknown analytical signal of urine is eliminated in the MISF spectrum obtained, be means of its first derivative. A calibration graph was constructed by measuring first derivative values at lambda ex = 357nm and lambda em = 392 nm. Analytical parameters of the proposed method were calculated according to the error propagation theory. The sensitivity, repeatability, reproducibility and limit of determination achieved with the proposed method are adequate for the determination of amiloride in urine.

Phosphorimetric determination of dipyridamole in pharmaceutical preparations.

Room temperature phosphorescence was applied to the determination of dipyridamole in pharmaceutical preparations. The response was linear in the concentration range 100-1600 ng ml-1. The use of phosphorescence enhancers such as thallium(I) nitrate (external heavy atom), sodium dodecyl sulfate (microemulsion stabilizer) and sodium sulfite (deoxygenation agent) was studied and optimized to obtain maximum sensitivity and adequate selectivity. The determination was performed in 0.026 M sodium dodecyl sulfate, 0.0156 M thallium nitrate and 0.02 M sodium sulfite. The pH value was 11.5, adjusted by adding sodium hydroxide. The phosphorescence was totally developed in 15 min, after that the intensity was measured at lambda ex = 303 nm and lambda em = 616 nm. The recovery of the method was tested on commercial formulations containing dipyridamole. The recoveries obtained were 94.67 +/- 0.58% for Persantin and 96.75 +/- 1.37% for Asasantin. The overall least squares regression method was applied to find the most exact straight line that fits the experimental data. The detection limit according to the error propagation theory was 16.4 ng ml-1. The repeatability and relative standard deviation were also determined according to this theory.

Direct determination of dipyridamole in serum.

A new method for the determination of dipyridamole in serum for concentrations between 10 and 100 ng ml-1 by means of matrix isopotential synchronous fluorescence spectrometry and derivative techniques is proposed. This new method is useful for the determination of compounds in samples with unknown background fluorescence, such as dipyridamole in serum, without the need for tedious preseparation. The determination was performed in an ethanol/water medium (15% v/v) at a pH value of 10.0, provided by adding an ammonium chloride/ammonia buffer solution. Since dipyridamole is a stimulant which is very much used like a doping substance in sport, the method was successfully applied to the determination of dipyridamole in serum. Better sensitivity and repeatability are achieved for these matrices than with the fluorometric ones described in the literature. An exhaustive statistical analysis has been developed for all calibration graphs. This treatment includes robust regression such as least median of squares which also detects outliers and leverage points. The overall least-squares regression has been applied to find the more exact straight line which fits the experimental data. The error propagation has been considered to calculate the detection limit, determination limit, and the repeatability of the method.

[Lupus vulgaris as initial manifestation of asymptomatic pulmonary tuberculosis]. / Lupus vulgar como manifestación inicial de tuberculosis pulmonar inadvertida.

A clinical case of a male with lupus lesion localized in scalp associated to a bilateral cavitated pulmonary tuberculosis which was non symptomatic. The cutaneous symptoms of tuberculosis is reviewed because the rareness of this presentation.