Prognostic role for the derived neutrophil-to-lymphocyte ratio in early breast cancer: a GEICAM/9906 substudy

Purpose: Elevated markers of host inflammation, a hallmark of cancer, have been associated with worse outcomes in several solid tumors. Here, we explore the prognostic role of the derived neutrophil-to-lymphocyte ratio (dNLR), across different tumor subtypes, in patients with early breast cancer. Patients and methods: This was a retrospective analysis of 1246 patients with lymph node-positive, operable early breast cancer enrolled in the GEICAM/9906 trial, a multicenter randomized phase 3 study evaluating adjuvant chemotherapy. dNLR was calculated as the ratio of neutrophils and the difference between total leukocytes and neutrophils in peripheral blood before chemotherapy. Disease-free survival (DFS) and overall survival were explored using a Cox proportional hazard analysis. Results: The analysis comprised 1243 (99.8%) patients with dNLR data, with a median follow-up of 10 years. Data on intrinsic subtypes were available from 818 (66%) patients (luminal A 34%, luminal B 32%, HER2-enriched 21% and basal-like 9%). Median dNLR was 1.35 [interquartile range (IQR) 1.08-1.71]. In the whole population, dNLR was not prognostic after adjustment for clinico-pathological factors. However, dNLR ≥ 1.35 was independently associated with worse DFS in the hormone receptor-negative/HER2+ population (HR 2.86; p = 0.038) and in patients with one to three lymph node metastases (HR 1.32, p = 0.032). There was a non-significant association with worse DFS in non-luminal and in HER2-enriched tumors (HR 1.40, p = 0.085 and HR 1.53, p = 0.067). No significant interaction was observed between the treatment arm and dNLR. Conclusion: Elevated dNLR appears to be an adverse prognostic factor in hormone receptor-negative early breast cancer

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A definition for aggressive disease in patients with HER-2 negative metastatic breast cancer: an expert consensus of the Spanish Society of Medical Oncology (SEOM)

Purpose. To converge on an expert opinion to define aggressive disease in patients with HER2-negative mBC using a modified Delphi methodology. Methods. A panel of 21 breast cancer experts from the Spanish Society of Medical Oncology agreed upon a survey which comprised 47 questions that were grouped into three sections: relevance for defining aggressive disease, aggressive disease criteria and therapeutic goals. Answers were rated using a 9-point Likert scale of relevance or agreement. Results. Among the 88 oncologists that were invited to participate, 81 answered the first round (92%), 70 answered the second round (80%), and 67 answered the third round (76%) of the survey. There was strong agreement regarding the fact that identifying patients with aggressive disease needs to be adequately addressed to help practitioners to decide the best treatment options for patients with HER2-negative mBC. The factors that were considered to be strongly relevant to classifying patients with aggressive HER2-negative mBC were a high tumor burden, a disease-free interval of less than 12-24 months after surgery, the presence of progressive disease during adjuvant or neoadjuvant chemotherapy and having a triple-negative phenotype. The main therapeutic goals were controlling symptoms, improving quality of life and increasing the time to progression and overall survival. Conclusions. High tumor burden, time to recurrence after prior therapy and having a triple-negative phenotype were the prognostic factors for which the greatest consensus was found for identifying patients with aggressive HER2-negative mBC. Identifying patients with aggressive disease leads to different therapeutic approaches (AU)

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Medical oncology future plan of the Spanish Society of Medical Oncology: challenges and future needs of the Spanish oncologists

Purpose. The SEOM Future Plan is aimed at identifying the main challenges, trends and needs of the medical oncology speciality over the next years, including potential oncologist workforce shortages, and proposing recommendations to overcome them. Methods. The estimations of the required medical oncologists workforce are based on an updated Medical Oncologist Register in Spain, Medical Oncology Departments activity data, dedication times and projected cancer incidence. Challenges, needs and future recommendations were drawn from an opinion survey and an advisory board. Results. A shortage of 211 FTE medical oncologist specialists has been established. To maintain an optimal ratio of 158 new cases/FTE, medical oncology workforce should reach 1881 FTE by 2035. Conclusions. Main recommendations to face the growing demand and complexity of oncology services include a yearly growth of 2.5% of medical oncologist’s workforce until 2035, and development and application of more accurate quality indicators for cancer care and health outcomes measure (AU)

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Equity, barriers and cancer disparities: study of the Spanish Society of Medical Oncology on the access to oncologic drugs in the Spanish Regions

Purpose. The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. Methods. An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. Results. 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. Conclusions. The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions (AU)

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SEOM Clinical Guideline update for the prevention of chemotherapy-induced nausea and vomiting (2016)

Chemotherapy-induced nausea and vomiting is one of the most worrisome adverse effects of chemotherapy for cancer patients. It can cause severe discomfort and affect the quality of life. In recent years, the incorporation of new drugs has increased the efficacy of antiemetic treatments in the control of emesis associated with chemotherapy. This guideline, in which we give some treatment recommendations with level of evidence and grade of recommendation, provides an update of the previously published guideline of the Spanish Society of Medical Oncology and represents our continued commitment to improving supportive care in cancer patients (AU)

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Impacto de la metodología Lean en la mejora de procesos asistenciales y niveles de satisfacción en la atención de pacientes en un laboratorio clínico / Impact of Lean methodology to improve care processes and levels of satisfaction in patient care in a clinical laboratory

Introducción. La aplicación de la metodología Lean en las instituciones de salud es una herramienta efectiva para mejorar la capacidad y el flujo de trabajo, así como para incrementar el nivel de satisfacción de pacientes y empleados. Objetivo. Optimizar el tiempo de atención de los pacientes ambulatorios en un laboratorio clínico mediante la implementación de una metodología basada en la organización de procesos operativos, para mejorar la satisfacción del usuario y reducir el número de quejas por demoras en la atención. Materiales y métodos. Se implementó un estudio cuasi experimental de antes y después, realizado entre octubre de 2011 a septiembre de 2012. Se emplearon gráficos X Barr y S para observar los promedios en los tiempos de atención y su desviación estándar. La satisfacción de los usuarios se evaluó mediante encuestas de servicio. Resultados. Se observó una disminución de hasta 9 min en los tiempos de atención de los pacientes, desde su llegada hasta su salida del laboratorio, y una disminución del 73% en las quejas por demora en la atención. A pesar de la alta rotación del personal y del incremento del 38% en el número de pacientes atendidos, se adquirió una cultura de empoderamiento y mejora continua, así como mayor eficiencia y productividad en el proceso de atención; lo cual se vio reflejado por el mantenimiento de los estándares 12 meses después de la implementación. Conclusión. La metodología Lean es una herramienta viable para mejorar los procesos de los laboratorios clínicos, mejorando su eficiencia y eficacia (AU)

Introduction. The application of the Lean methodology in health institutions is an effective tool to improve the capacity and workflow, as well as to increase the level of satisfaction of patients and employees. Objective. To optimise the time of outpatient care in a clinical laboratory, by implementing a methodology based on the organisation of operational procedures to improve user satisfaction and reduce the number of complaints for delays in care. Material and methods. A quasi-experimental before and after study was conducted between October 2011 to September 2012. XBar and S charts were used to observe the mean service times and standard deviation. The user satisfaction was assessed using service questionnaires. Results. A reduction of 17 minutes was observed in the time of patient care from arrival to leaving the laboratory, and a decrease of 60% in complaints of delay in care. Despite the high staff turnover and 38% increase in the number of patients seen, a culture of empowerment and continuous improvement was acquired, as well as greater efficiency and productivity in the care process, which was reflected by maintaining standards 12 months after implementation. Conclusion. Lean is a viable methodology for clinical laboratory procedures, improving their efficiency and effectiveness (AU)

SEOM Guidelines 2015: a new era in the collaboration with the Spanish Cancer Research Cooperative Groups

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SEOM clinical guidelines in early-stage breast cancer 2015

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cáncer (AU)

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SEOM guidelines 2014: improving quality to increase its usefulness

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SEOM guidelines on hydroelectrolytic disorders

Hydroelectrolytic disorders are one of the most common metabolic complications in cancer patients. Although often metabolic alterations affecting various ions are part of the manifestations of the oncological disease, even in the form of paraneoplastic syndrome, we must not forget that very often, these disorders could be caused by various drugs, including some of the antineoplastic agents most frequently used, such as platin derivatives or some biologics. These guidelines review major management of diagnosis, evaluation and treatment of the most common alterations of sodium, calcium, magnesium and potassium in cancer patients. Aside from life-sustaining treatments, we have reviewed the role of specific drug treatments aimed at correcting some of these disorders, such as intravenous bisphosphonates for hypercalcemia or V2 receptor antagonists in the management of syndrome of inappropriate antidiuretic hormone secretion-related hyponatremia (AU)

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CLASIFICACIÓN DE LATIDOS DE CONTRACCIÓN VENTRICULAR PREMATURA BASADOS EN MÉTODOS DE APRENDIZAJE NO SUPERVISADO / CLASSIFICATION OF PREMATURE VENTRICULAR CONTRACTION BEATS BASED ON UNSUPERVISED LEARNING METHODS / CLASSIFICAÇÃO DE PREMATUROS BATIDAS CONTRAÇÃO VENTRICULAR BASEADO SUPERVISIONADO MÉTODOS DE APRENDIZAGEM

Las enfermedades cardiovasculares son la principal causa de mortalidad en el mundo, por lo que el desarrollo de algoritmos que detecten arritmias cardíacas en tiempo real se ha convertido en un campo de investigación importante. El desarrollo de estos algoritmos ha conllevado a la mejora de dispositivos cardiacos portátiles. Este artículo presenta el desempeño de dos algoritmos basados en aprendizaje de máquina no supervisado para la detección de latidos de contracción ventricular prematura en la señal ECG. Los latidos se extraen de las bases de datos del MIT-BIH, los cuales fueron pre-procesados y segmentados por el grupo de investigación de Dinámica Cardiovascular de la UPB. La Transformada Wavelet Discreta, el Análisis de Componentes Principales y un método híbrido propuesto son implementados para la extracción de características y reducción de dimensiones, a partir de los cuales se generan 8 espacios de características para la evaluación de los algoritmos. Kmeans y Mapas auto-organizados son desarrollados y comparados en términos de precisión y costo computacional. Se logró una especificidad del 96.22 % y una sensibilidad del 95.04 % con un tiempo de ejecución de 79.41µs por latido. Los resultados permiten concluir que estos métodos pueden implementarse en aplicaciones de detección de arritmias en tiempo real debido a su bajo costo computacional.

Cardiovascular diseases are the principal cause of mortality in the world, so that the development of algorithms that detect cardiac arrhythmias in real time has become an important field of research. The development of these algorithms has led to the improvement of wearable cardiac devices. This paper presents the performance of two algorithms based in unsupervised learning methods for the detection of Premature Ventricular Contraction in the ECG signal. The beats are extracted from MIT-BIH databases, which were preprocessed and segmented by the UPB’s Dynamic Cardiovascular research group. The Discrete Wavelet Transform (DWT), Principal Component Analysis (PCA) and a proposed hybrid method are implemented for the feature extraction and dimension reduction, from which 8 feature spaces are generated and tested. Kmeans and Self Organizing Maps are developed and compared in terms of accuracy and computational cost. Specificity of 96.22 % and sensitivity of 95.94% with 79.41µs per beat are accomplished. The results show that these methods can be implemented in applications of real time arrhythmia detection because of their low computational cost.

A doença cardiovascular é a principal causa de morte em todo o mundo, de modo que o desenvolvimento de algoritmos para detectar arritmias cardíacas, em tempo real, tornou-se um importante campo de pesquisa. O desenvolvimento desses algoritmos tem levado a melhores dispositivos cardíacos portáteis. Este artigo apresenta o desempenho dos dois com base na aprendizagem de máquina sem supervisão para detecção de batidas de contração ventriculares prematuras nos algoritmos de sinais de ECG. As batidas são extraídos das bases de dados do MIT-BIH, que foram pré-processados e segmentado pelo grupo da UPB Cardiovasculares Dynamics pesquisa. A Transformada Wavelet Discreta, Análise de Componentes Principais e uma abordagem híbrida proposta são implementadas para extração de características e redução de dimensão, a partir do qual 8 espaços de recursos para a avaliação dos algoritmos são gerados. Kmeans e mapas de auto-organização são desenvolvidos e comparados em termos de precisão e custo computacional. A especificidade de 96,22% e uma sensibilidade de 95,04% com um tempo de execução de 79.41µs por batida foi alcançado. Os resultados mostram que estes métodos podem ser implementados em aplicações de detecção de arritmia em tempo real, devido ao seu baixo custo computacional.

SEOM Guidelines 2013: a response to the needs of Spanish oncologists

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SEOM clinical guidelines: a consolidated project

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Definición de un ROLE 1 sobre contenedor «6 en 1» e la Unidad Médica Aérea de Apoyo al Despliegue (UMAAD) Zaragoza / Definition Role 1 in container 6 to 1 from UMAAD Zaragoza

Introducción: La Unidad Médica Aérea de Apoyo al Despliegue (UMAAD) de Zaragoza posee un contenedor ISO de 20 pies, expandible (6 en 1) para su uso como Role 1 (Atención primaria y de Urgencia) dentro del despliegue de un destacamento del Ejército del Aire. Material: Definición de la disposición interna, sistemas auxiliares y material de un Role 1 montado sobre un contenedor 6 en 1. Funcionamiento: El contenedor 6 en 1 de la UMAAD, es un elemento de gran utilidad, versatilidad y funcionalidad que permite emplazar, en un espacio limitadoy en muy poco tiempo, una Instalación de Tratamiento Médico con capacidad Role 1 con elevado potencial de transformación interna, lo cual resulta extremadamente útil para garantizar el nivel asistencial adecuado en Atención Primaria y de Urgencias para el personal desplegado en una misión. El tiempo de despliegue y montaje del contenedor, en dependencia de la orografía del suelo, puede oscilar entre 30 y 120 minutos, y la instalación del material y sistemas auxiliares, necesario para ser operativo en unas 2-4 horas. El personal que se precisaríapara este montaje no supera las 6 personas. Además dicho material puede ser trasportado por vía terrestre, aérea y marítima lo que lo hace muy adecuado para su uso en el medio militar. Conclusiones: El uso de un contenedor 6 en 1 para su utilización como puesto de AtenciónPrimaria y Urgencias (Role 1), mejora la calidad de la atención al paciente y amplía la capacidad de servicios que se pueden realizar enoperaciones de proyección del personal del Ejército del Aire y, en general, de las Fuerzas Armadas (AU)

Introduction: Air Medical Deployment Support Unit (UMAAD) of Zaragoza has a 20-feet ISO container, expandable (6 in 1) to use as a Role 1 (Primary Care and Emergency) in the deployment of any detachment of Spanish Air Force. Material: Definition of internal arrangement, auxiliarysystems and supplies for a Role 1 mounted on a 6 in 1 container. Functions: The UMAAD’s 6 in 1 container is an element of great utility, versatility and functionality in order to have enough space in a very short time to deploy as a Role 1, with powerful inner transformation that makes it veryuseful for primary care and emergency staff deployed in a mission. Deployment time and installation of the container, depending on the topographyof the soil, can vary between 30 and 120 minutes, and the installation of equipment and auxiliary systems required to be operational in about 2-4 hours. Personnel required for this installation would be about six people. Also this material can be transported by land, sea and air making it very suitable for its use by the military. Conclusions: The 6 in 1 container usage as a post of Primary Care and Emergency (Role 1) improves the quality of patient care and extends the function capability that can be performed on projected operations staff of the Air Force and, in general, Armed Forces (AU)

El interferón alfa-2b recombinante mejora la disfunción cognitiva en pacientes con esclerosis múltiple / Interferon alpha-2b recombinant improved the cognitive dysfunction in patients with relapsing-remitting multiple sclerosis

Introducción. Ensayos clínicos recientes indican que el interferón (IFN)alfa-2b recombinante, parece ser útil en la forma exacerbación-remisión (ER) de la esclerosis múltiple (EM). Un 70 por ciento los pacientes con EM en Cuba tienen disfunción cognitiva. Objetivo. Evaluar la eficacia del IFNa2b en los trastornos cognitivos de la EM. Pacientes y métodos. 57 pacientes con EM-ER clínicamente definida y confirmada por RM, del ensayo clínico en Cuba, fase III, multicentro, aleatorizado, doblemente ciego y controlado con placebo. Los pacientes se distribuyeron en: grupo I, con 10 millones (MI) de UI de IFNalf-a2b (Heberon-R ®) intramuscular; el grupo II, con 3 MI IFNalfa-2b y grupo III,con placebo, dos veces a la semana, durante dos años. Las evaluaciones fueron a ciegas, al inicio y al final, mediante la escala neuropsicológica de Luria, Benton visual retention test, escala verbal WAISR ( Weschler adult intelligence-revised) y el PASAT-3 (paced auditory serial addition test). La detección de anticuerpos neutralizantes (ACN) al IFNalfa-2b, se realizó semestralmente. Resultados. Los resultados iniciales no demostraron diferencias significativas entre los grupos para las variables demográficas, clínicas y de discapacidad. Los resultados del Luria fueron: placebo [inicial (I)/final (F)] 2,85 ñ 1,66/2,90 ñ 1,97 (p = 0,723); IFNalfa-2b 3 MI (I/F): 2,50 ñ 1,34/1,39 ñ 1,85 (p = 0,029); IFNalfa-2b 10 MI (I/F): 3,22 ñ 1,69/2,17 ñ 1,50 (p = 0,006). Al fusionar los dos grupos IFNa2b frente a placebo se obtuvo p = 0,021 frente a 0,367. En el Benton, los resultados fueron: placebo (I/F): 5,15 ñ 1,76/5,05 ñ 2,11 (p = 0,893); IFNalfa-2b 3 MI (I/F): 5,50 ñ 1,10/6,22 ñ 1,31 ( p = 0,047); IFNalfa-2b 10 MI (I/F): 4,67 ñ 1,85/5,78 ñ 1,35 (p = 0,005). Al unir los grupos IFNalfa-2b frente a placebo, se obtuvo p = 0,181 frente a 0,440. En el test WAIS se encontró: placebo (I/F): 5,25 ñ 1,25/5,05 ñ 1,57 (p = 0,354); IFNalfa-2b 3 MI (I/F): 5,17 ñ 1,34/6,06 ñ 1,21 ( p = 0,022); IFNalfa-2b 10 MI (I/F): 4,56 ñ 1,38/5,39ñ1,29 (p = 0,007). Al comparar los grupos IFNalfa-2b frente a placebo (I/F) se obtuvo p = 0,026 frente a 0,216. Los resultados del PASAT-3 fueron: placebo (I/F): 44,55 ñ 10,86/41,95 ñ 13,74 (p = 0,655); IFNa2b 3 MI (I/F), 45,72 ñ 10,61/49,94 ñ 11,68 ( p = 0,015); IFNalfa-2b 10 MI (I/F), 42,67 ñ 11,04/48,72 ñ 8,84 (p = 0,003). Al comparar los grupos IFN frente a placebo, con el PASAT-3, se obtuvo p = 0,033 frente a 0,621. Los ACN contra el IFNalfa-2b se detectaron en un 3,5 por ciento de los casos. Conclusiones. El IFNa2b mejora las alteraciones cognitivas en la EM-ER. Esta mejoría es dependiente de la dosis y la frecuencia de ACN es muy baja (AU)

Introduction. Some experimental, Phase II clinical trials and the preliminary reports of the Cuban Phase III clinical trial indicate that alpha-IFN (IFN) may be useful in relapsing-remitting (RR) multiple sclerosis (MS). The reports in Cuba showed that 70% of the MS patients have cognitive dysfunction. Objective. To assess the efficacy of IFN-alpha 2b recombinant in the cognitive dysfunction of RR-MS. Patients and methods. 57 RR-MS clinical definite (Poser et al) patients from the randomised, double-blind, placebo-controlled study of 225 patients with RR-MS and brain MRI confirmed. Patients were randomly assigned to receive intramuscular IFN alpha-2b (Heberon-R ®) 10 million IU (high dose), 3 million IU (low dose) or placebo twice week for 2 years. Outcome results were blinding evaluated considering changes in the following tests: Luria, WAIS, Benton and PASAT-3. Adverse events and side effects were not evaluated to maintain physician blinding. Results. The initial comparison of the groups did not show any differences among the placebo (n= 20), low dose (n= 18) and high dose (n= 19) considering age (p= 0.234), gender, ethnic group (p= 0.012), years ill (p= 0.787), EDSS (p=0.203) and rate of relapses (p= 0.432).The Luria’s Test showed an improved in the low dose group from 2.50±1.34 to 1.39±1.85 (p= 0.029) and in the high dose group from 3.22±1.89 to 2.17±1.50 (p= 0.006) vs placebo 2.85±1.66 to 2.90±1.97 (p=0.723). The results of the Benton’s test demonstrated that the low dose group had an improved from 5.50±1.10 to 6.22±1.31 (p= 0.047), in the high dose group from 4.87±1.85 to 5.78±1.35 (p= 0.005) where as in the placebo group worse from 5.15±1.76 to 5.05±2.11 (p= 0.893). The WAIS test showed the same results, the low dose group increased from 5.17±1.34 to 6.06±1.21 (p= 0.022), the high dose group from 4.56±1.38 to 5.39±1.29 (p= 0.007) and the placebo group worse from 5.25±1.25 to 5.05±1.57 (p=0.354). Finally, the PASAT-3 test increased in the IFNs groups: from 45.72±10.61 to 49.94±11.68 (p= 0.015) in the low dose group, from 42.67±11.04 to 48.72±8.84 (p= 0.03) in the high dose group, but in the placebo group worse from 44.55±10.86 to 41.95±13.74 (p= 0.655). Conclusion. IFN alpha improved the cognitive dysfunction in RR-MS patients. The higher dose is more beneficial (AU)

Disorders of thyroid hormones in non-insulin-dependent diabetes mellitus

INTRODUCTION: In a previous study of patients with non-insulin-dependent diabetes mellitus (NIDDM) of less than 5 years' duration at the HCQ "Hermanos Ameijeiras", Cuba, we found abnormal values of T3 at iniitial evaluation. It was proved that the cause was an increase in the activity of the enzyme catalysing the process of peripheral deiodination of T4 to T3. OBJECTIVE: To examine these variables in a larger sample. SUBJECTS AND METHODS: One hundred and forty patients with NIDDM of 1-25 years' duration being treated by diet, and/or oral hypoglycaemic agents, were studied T3, T4, and insulin were measured by radio-immunoassay; glucose, by glucose-oxidase; cholesterol, triglycerides and HDL-cholestrol by the Trinder method; LDL and VLDL by the Ellefson formula; glycosylated haemoglobin by ion exchange chromatography, and microalbuminuria by an immuno-colorimetric semiquantitative method. The sample was divided into 5 groups: 1-2 years, 3-4 years, 5-6 years, 7-15 years, and more than 15 years' duration of diabetes mellitus. RESULTS: The results confirmed the previous findings that there was a marked increase in T3 (4.87, 4.49, 3.1, 2.8, 2.9 mmol/l, respectively) in the time of evolution but diminishing progressively as the time of evolution increases and normalizing in the 5-6 year group. There were no notable differences in T4 in the 5 groups of healthy controls (102, 113, 96, 94, 99 mmol/l). The blood glucose levels were higher than in the healthy population but a point of inflection was noted in the 5th -6th year of evolution (8.6, 8.2. 7.02, 8.4, 8.3 mmol/l). The insulin values were noted to have a greater variation between 1-2 years and 3-4 years, supposedly a treatment effect as in the 1-2 year group. There were patients who had not started treatment but the insulin in the 3-4 year group decreased with the introduction of treatment (48.7, 17.9, 32.1, 36.6, 39.5 mU/ml). Glycosylated haemoglobin showed a point of inflection in the 5th-6th year (7.2, 6.3, 8.2, 7.9, 8.5 percent). Lipid metabolism indicators, cholesterol (4.7, 5.2, 5.6, 5.74, 5.5 mmol/l), triglyceride (1.34, 2.01, 1.33, 1.95, 1.65 mmol/l) and low density lipoprotein (2.99, 3.14, 3.97, 3.95, 3.63 mmol/l) progressively increased with time of evolution. Microalbuminuria behaved the same (25, 12.4, 14.5, 33.4, 27.3 mg/l), showing a higher value at 1-2 years and diminishing between 3 and 6 years but increasing thereafter.(Au)