Caracterización del uso de metadona en pacientes paliativos en el Instituto Nacional del Cáncer, Santiago de Chile / Characterization of methadone use in palliative patients at the National Cancer Institute, Santiago, Chile

OBJETIVOS: realizar un estudio de tipo descriptivo y retrospectivo para caracterizar el uso y efecto de metadona en una población de pacientes de la unidad de cuidados paliativos del Instituto Nacional del Cáncer. MATERIALES Y MÉTODOS: los datos analizados se obtuvieron desde los registros de la farmacia y las fichas clínicas de los pacientes de la unidad de cuidados paliativos del Instituto Nacional del Cáncer que estaban siendo tratados con metadona durante el mes de agosto de 2013. las variables cuantificadas fueron edad, sexo, diagnóstico oncológico, tipo de dolor, motivo de indicación de metadona, duración del tratamiento, dosis utilizadas, respuesta analgésica y uso concomitante con analgésicos no opioides. RESULTADOS: la población de pacientes bajo control mensual en la unidad de cuidados paliativos al mes de agosto fue de 445 pacientes. en el estudio se incluyeron a 31 pacientes que estaban en ese periodo tratados con metadona, lo que representa un 7% del total de pacientes. la indicación, según tipo de dolor, fue en un 80,6% por dolor de tipo neuropático o mixto. la indicación de metadona se debió, en un 68%, a una rotación de opioides y solo en un 3% fue por indicación primaria. la dosis promedio diaria fluctuó entre 16,7 mg, al inicio del tratamiento; y 26,1 mg, al momento del estudio o periodo de observación. la mediana de uso fue de 211 días. la intensidad del dolor, medida por la escala numérica verbal, fue de 8,3 ± 0,3 mg al inicio del tratamiento y 5,4 ± 0,6 mg durante el control de agosto de 2013, lo que significa una disminución promedio de 34,9%. DISCUSIÓN: el uso de metadona en la unidad de cuidados paliativos del Instituto Nacional del Cáncer está en concordancia con las propuestas internacionales, indicándose principalmente como rotación de opioides y en el tratamiento del dolor neuropático. el análisis de las fichas mostró utilización de dosis bajas de metadona (menores de 30 mg), con pequeños incrementos de dosis durante el período de tratamiento, obteniéndose como resultado una reducción significativa del dolor.

OBJETIVES: to carry out a descriptive and retrospective study to characterize the use and effect of methadone in a group of patients of the Palliative Care Unit of the National Cancer Institute. MATERIALS AND METHODS: the information was obtained from the patient pharmacy and clinical records at the palliative care unit of the National Cancer Institute who were being treated with methadone during the month of august, 2013. the variables assessed were age, sex, oncology diagnosis, type of pain, reason for methadone prescription, treatment duration, dosage, pain response and associated use of non- opioid analgesics. RESULTS: the patient group under monthly monitoring at the palliative care unit in august was made up of 445 people. the study included 31 patients who at that time were being treated with methadone, 7% of the total. the indication according to the type of pain was in an 80.6% caused by a neuropathic or mixed pain. a 68% of the methadone indication was caused by an opioid rotation and only a 3% by a primary indication. the average daily dose went from 16.7 mg at the beginning to 26.1 mg at the moment the study or observation period was carried out. the use average was of 211 days. The pain intensity, using a numeric scale, was of 8.3 ± 0.3 mg at the beginning of the treatment and a 5.4 ± 0.6 mg during the august 2013 control, which means an average decrease of 34,9 %. DISCUSSION: the use of methadone at the palliative care unit of the National Cancer Institute is in accordance with the international proposals, being indicated mostly as opioid rotation and in the neuropathic pain treatment. the record analysis showed a low dose use of methadone (lower than 30 mg), with small dose increase during the treatment period, getting a significant pain decrease as a result

Superioridad del nuevo puntaje de riesgo ACC/AHA 2013 por sobre el puntaje de Framingham, en la predicción de riesgo de mortalidad cardiovascular en Santiago / Evaluation the American College of Cardiology and American Heart Association Predictive score for cardiovascular diseases

Background: Recently, the American College of Cardiology and American Heart Association (ACC/AHA) proposed a new cardiovascular risk (CV) score. Aim: To evaluate the new risk score (ACC/AHA 2013) in a Chilean population. Material and Methods: Between 2002 and 2014, body mass index (BMI), waist circumference, blood pressure, lipid profile and fasting blood glucose levels were measured and a survey about CV risk factors was responded by 3,284 subjects aged 40 to 79 years (38% females), living in urban Santiago. ACC/AHA 2013, FRAM and Chilean FRAM scores were calculated. All-cause mortality was determined in July 2014 by consulting the Death Registry of the Chilean Identification Service, with an average follow up of 7 ± 3 years. Results: The prevalence of risk factors were 78% for dyslipidemia, 37% for hypertension, 20% for smoking, 7% for diabetes, 20% for obesity and 54% for physical inactivity. The mean FRAM, Chilean FRAM and ACC/AHA scores were 8, 3 and 9%, respectively. During follow-up, 94 participants died and 34 deaths were of cardiovascular cause. Participants who died had a higher prevalence of hypertension (p < 0.01) and diabetes (p < 0. 01) and tended to be older (p = 0.06). The FRAM score for 10 years for deceased and surviving patients was 12 and 8%, respectively (p = NS). The figures for the Chilean FRAM were 5 and 2%, respectively (p = 0.09). The figures for the ACC/AHA 2013 score were 33 and 9%, respectively (p = 0.04). According to receiver operating characteristic curves, ACC/AHA 2013 had a higher area under de curve for CV mortality than FRAM and Chilean FRAM. Conclusions: The new ACC/AHA 2013 score, is better than traditional FRAM and Chilean FRAM scores in predicting cardiovascular mortality in a low risk population.

Uso de opioides en pacientes paliativos oncológicos al momento de fallecer: “el mito de la morfina” / Use of opioids in palliative cancer patients at the time of his death: the myth of morphine

Objetivos: determinar cuáles fueron los opioides usados al momento de morir, tiempo de uso e incremento de dosis. Materiales y Métodos: Pacientes paliativos ingresados el año 2008 al Instituto Nacional del Cáncer. Los datos fueron obtenidos del libro de ingresos y registro informático de recetas. Resultados: Ingresaron 456 pacientes, de éstos fallecieron 170 (37 por ciento), con mediana de edad de 66 años (16-97) y 53 por ciento mujeres. Al momento del fallecimiento, un 14 por ciento no estaba recibiendo opioides. Los opioides utilizados fueron codeína, 11,7 por ciento; tramadol, 32,4 por ciento; oxicodona, 0,7 por ciento; morfina, 37,2 por ciento; metadona, 4,8 por ciento; buprenorfina TTS, 10,3 por ciento; y fentanilo TTS, 2,8 por ciento. En todos, las dosis promedio fueron bajas (morfina, 26,9 mg/día; metadona, 17,9 mg/ día; tramadol, 142,8 mg/día; buprenorfina, 19 ug/h; y fentanilo, 19,5 ug/h). No se evidenció un incrementosignificativo en las dosis. El tiempo promedio de uso desde el último cambio de opioide fue 41,3 DE+63,5 días con una mediana de 26 días (1 a 366). No se encontró diferencia entre los opioides. Discusión: La mitad de los pacientes fallecidos estaban en OMSIII. De los usuarios de opioides potentes, solo un 37 por ciento estaba con morfina. Las dosis promedio de todosfueron bajas. El tiempo transcurrido entre el inicio del opioide y la muerte no difirió entre opioides. En suma, no todos los pacientes paliativos en nuestra población falleció recibiendo morfina, no se evidenciaron diferencias en el tiempo de uso del opioide ni un aumento de la dosis, lo cual desmitifica dos creencias: “si uso morfina me voy a morir antes” y “si uso morfina deberé aumentar las dosis y me haré dependiente”.

Objectives: to determine which were the opioids used at the time of death, time usage and increasing doses. Materials and Methods: Palliative patients admitted to the National Cancer Institute in 2008. Data were obtained from the book income and prescription computer records. Results: 456 patients were treated, 170 died (37 percent), with median age of 66 (16-97) and 53 percent women. At death time, 14 percent was not receiving opioids. Used opioids were 11.7 percent codeine; 32.4 percent tramadol; 0.7 percent oxycodone; 37.2 percent morphine; 4.8 percent methadone; 10.3 percent TTS buprenorphine and 2.8 percent TTS fentanyl. All average doses were low (morphine 26,9 mg/day, methadone 17,9 mg/ day, tramadol, 142,8 mg/ day, buprenorphina 19 ug/h and fentanyl 19,5 ug/h). A significant increase in dose was not observed. Average time since the last change of opiode was 41.3 DE+63.5 days with a median of 26 days (1-366), no difference was found between different opioids. Discussion: Half of the patients who died were in OMSIII. Only 37 percent of strong opioids users was using morphine. The average doses of all were low. Time between start opioid use and death was no different for different opioids. So not all palliative patients died using morphine, and no differences were observed in opioids time of use, or increasing doses which demystifies two beliefs: “If I use morphine I will die prematurely” and “If I use morphine, I will increase dose and I will be dependent ”.

Caracterización de pacientes hospitalizados con neoplasia activa y diagnóstico de enfermedad tromboembólica venosa mediante la puntuación de Khorana en el Instituto Nacional del Cáncer / Khorama score as a predictive tool for thromboembolic events in high risk patients

Background: There is an established relation between cancer and the development of thromboembolic venous disease. Khorana et al developed a predictive score using clinical characteristics and laboratory values to stratify patients according to their risk. Aim: To characterize using Khorana score, patients with active cancer and a diagnosis of thromboembolic disease during hospitalization in an oncology hospital. Material and Methods: Review of records of the pharmacy of the hospital, selecting patients who received heparin in therapeutic doses during their hospitalization. Using laboratory values available in the medical records, the Khorama score was calculated. Results: Twenty seven patients with thromboembolic events, aged 60 ± 2 years (56% males) were selected for the study. Eighty percent of them were catalogued in the intermediate and high risk group according to Khorana score. Conclusions: Khorana score is a simple scale that might be useful to establish early prophylactic measures in patients with high risk for thromboembolic events, especially those with cancer.

Niveles de fosfolipasa A2 asociada a lipoproteína en sujetos sin enfermedad coronaria con riesgo cardiovascular variable / Association of lipoprotein-associated phospholipase activity A2 with cardiovascular risk factors

Background:Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory biomarker involved in atherosclerosis and directly associated with cardiovascular events. Aim: To determine Lp-PLA2 levels in asymptomatic subjects with differing cardiovascular risk. Material and Methods: We studied 152 subjects aged 46 ± 11 years (69 women). We recorded traditional cardiovascular risk factors, creatinine, ultrasensitive C-reactive protein, fibrinogen, fasting lipids, blood sugar and activity levels of Lp-PLA2. Cardiovascular risk was classified according to the number of risk factors of each subject (0,1-2 or ≥ 3 risk factors). Besides, we calculated global Framingham risk score. Results: The average Framingham score of participants was 6%. Twenty percent of participants had no risk factors, 46% had 1 or 2 and 34% had ≥ 3. Mean Lp-PLA2 levels were 185 ± 48 nmol/ml/min (201 ± 49 in men and 166 ± 38 in women). Lp-PLA2 correlated significantly (p < 0,05 for all) with non-HDL cholesterol, LDL, HDL, creatinine, waist circumference, body mass index and Framingham risk score. There was no correlation with blood sugar, C-reactive protein, fibrinogen or smoking status. Lp-PLA2 levels were significantly higher according to the number of risk factors: 0 factors: 163 ± 43, 1-2 factors: 185 ± 45 and ≥ 3 factors: 201 ± 47 nmol/ml/min, respectively. Linear regression analysis showed that the best predictor of Lp-PLA2 was non-HDL cholesterol (β= 0,74; p < 0,0001). Conclusions: Lp-PLA2 activity increased along with the number of cardiovascular risk factors and was correlated mainly with non -HDL cholesterol.

Rehabilitación cardiovascular y ejercicio en prevención secundaria / Exercise and cardiac rehabilitation in secondary cardiovascular prevention

Exercise and cardiac rehabilitation are indications with type I A evidence in most secondary cardiovascular prevention guidelines. Rehabilitation programs not only include exercise but also provide integral care and education about cardiovascular risk factors. However there is a paucity of such programs in Chile. Moreover there is a lack of awareness about the benefits of exercise and there is lack of knowledge about the details of exercise prescription in secondary prevention. Therefore, the divulgation of this knowledge is of utmost importance.

¿Sirven los marcadores de riesgo no tradicionales en la diferenciación del riesgo cardiovascular en adultos jóvenes con exceso de peso? / Carotid intima media thickness and C reactive protein among overweight or obese subjects without metabolic syndrome

Background: Recognizing cardiovascular risk in overweight adults is challenging, as they usually have a low Framingham risk score (FRAM). In these subjects, non-traditional biomarkers could improve risk stratification. Aim: To assess carotid intima media thickness (CIMT) and ultrasensitive C-reactive protein (usCRP) among overweight and obese subjects without metabolic syndrome (MetSyn). Subjects and Methods: In 1558 asymptomatic participants (816 women, 45 ± 11 years) we measured body mass index (BMI), waist circumference, blood pressure, lipid profile, blood glucose, FRAM, usCRP and CIMT. For analytical purposes, we divided the subjects in three groups according to BMI and number of ATPIII-MetSyn risk factors (RF): 1) BMI < 25 and < 3RF, 2) BMI ≥ 25 and < 3RF and 3) BMI ≥ 25 and ≥ 3RF. Results: Participants of group 2 (BMI ≥ 25 and < 3RF) had a low FRAM (8%). Compared with participants of group 1, they had a higher CIMT (0.61 ± 0.1 and 0.57 ± 0.09 mm, respectively, p < 0.01) and usCRP (2.1 ± 2.1 and 1.5 ± 1.9 mg/L respectively, p < 0.01). Conclusions: This study shows that although subjects with overweight/obesity without MetSyn have low cardiovascular risk based on FRAM, they have higher CIMT and usCRP than their normal weight counterparts.

Relación colesterol total a HDL y colesterol no HDL: los mejores indicadores lipídicos de aumento de grosor de la íntima media carotidea / Total/HDL cholesterol ratio and non HDL cholesterol as predictors for increased intima media thickness

Background: LDL, HDL cholesterol and triglycerides, are the most commonly used lipid cardiovascular risk predictor indicators. However population based studies have shown that non-HDL cholesterol and total/HDL cholesterol ratio are better predictors, are easy to measure and do not require fasting. Aim: To determine which lipid indicators are better determinants of subclinical atherosclerosis, measured by intima media thickness (IMT) among subjects without demonstrated atherosclerosis. Material and Methods: Lipid profile, height, weight, blood pressure and bilateral IMT, measured by ultrasound with automatic border recognition software, were assessed in 770 men and 854 women aged 45 ± 11 years, in Santiago de Chile. Results: Mean total cholesterol was 202, HDL 50, LDL 121, triglycerides 157 and non-HDL cholesterol 152 mg/dl. Total/HDL cholesterol ratio was 4.3. MeanIMTwas 0.62 mm. All lipid markers were significantly correlated with IMT. This correlation was higher for non-HDL cholesterol (r = 0.24, p < 0.0001) and total/HDL cholesterol ratio(r = 0.23, p < 0.0001). In both men and women, total/HDL cholesterol ratio was the best predictor of having an IMT over the 75th percentile (odds ratio 1.21, 95% confidence intervals 1.09-1.35, p < 0.01). Conclusions: Total/HDL cholesterol ratio was the best determinant of subclinical atherosclerosis.

Agregación de factores de riesgo cardiovascular y conciencia de enfermedad en trabajadores de un hospital universitario / Cardiovascular risk factors in a group of health care workers

Background: Health promotion can be carried out at work places. Aim: To assess cardiovascular risk factors among workers of a University hospital. Material and Methods: Cross sectional study of 888 participants (aged 41 ± 11 years, 76% women), who answered a survey about cardiovascular risk factors. Body mass index, waist, blood pressure and total cholesterol (TC) by capillary method were determined. Results: Self reported prevalence of risk factors were as follows: 19% of participants had high blood pressure, 30% hypercholesterolemia, 6% diabetes, 41% smoked, 88% were sedentary and 26% had a family history of cardiovascular diseases. Five percent of participants did not have any risk factor, 20% had one risk factor, 32% had two and 43% had three or more. The highest frequency of lack of awareness was about blood glucose values. A high blood cholesterol level was found in 27% of those reporting normal cholesterol levels. Likewise, a high body mass index was found in 18% of those reporting a normal weight. Conclusions: The prevalence of cardiovascular risk factors in this group of participants is similar to that found in the last national health survey in Chile. Noteworthy is the lack of awareness about these risk factors.

Perfil de riesgo cardiovascular en adultos jóvenes asintomáticos con grosor íntima media carotídeo elevado / Cardiovascular risk factors among young subjects with high carotid intima media thickness

Background: Cardiovascular risk factor (RF) assessment is essential to prevent and predict cardiovascular disease. The presence of RF at early ages, are determinant for the presence of atherosclerosis later in life. Aim: To determine the RF profile of young subjects with high carotid intima media thickness (CIMT). Material and Methods: We studied 689 subjects (50 percent women, mean age 36±6 years) from Santiago, Chile. We determined body mass index (BMI), waist circumference, blood pressure, fasting serum lipids, blood glucose and C-reactive protein. CIMT was assessed by ultrasound using an automatic border recognition software. Results: Body mass index, waist circumference, blood pressure and serum lipids were significantly higher among subjects located in the higher CIMT quartile. Also, subjects in the higher quartile of CIMT had a higher prevalence of three or more RF compared with the lower quartile (p = 0.01). Finally, individuals with three or more RF showed three times more risk of being in the higher CIMT quartile, than subjects with no RF (odds ratio = 3.1, p < 0.01). Conclusions: There is a negative influence of cardiovascular RF on CIMT among young subjects.

Hipertensión arterial: el factor de riesgo más importante para grosor íntima-media carotídeo elevado y placa carotídea en adultos de Santiago / Risk factors for a high carotid intima media thickness among healthy adults

Background: Carotid intima media thickness (CIMT) is a marker of cardiovascular damage that can be modified by traditional risk factors. Aim: To determine attributable risk factors for a high CIMT among healthy adults. Material ana Methods: A sample of 1270 individuáis (636 males and 634 femóles) aged 44 ±11 years, was studied. Blood pressure, weight, height, lipidprofile and blood glucose were measured in all. CIMT and thepresence of atheroscleroticplaques were determined by carotid ultrasound. Standard criteria were used to define hypertension, dyslipidemia and diabetes. Results: Mean CIMT in the sample studied was 0.62 ± 0.01 mm and percentile 75 was 0.67. The most important risk factor for a CIMT over percentile 75 and thepresence of atherosclerotic plaques was hypertension with attributable risks of 54 and 57 percent, respectively. Conclusions: In this sample, the main risk factor for a high CIMT was hypertension.

Actividad física y potencia aeróbica: ¿Cómo influyen sobre los factores de riesgo cardiovascular clásicos y emergentes? / Association between cardiorespiratory fitness and cardiovascular risk factors in healthy individuals

Background: Cardio respiratory fitness (FIT) is associated with a better profile in most modifiable cardiovascular risk factors (RF). In Chile, sedentary lifestyle is highly prevalent, reaching almost 90 percent. Aim: To determine the association between FIT and traditional and emergent RF in a primary prevention population. Material and methods: We prospectively studied 1973 subjects (36 percent women, mean age 56± 13 years) without history of cardiovascular disease and absence of ischemic changes on exercise testing. We assessed cardiovascular RF and determined body mass index (BMI), waist circumference, systolic and diastolic blood pressure, fasting blood lipids, glucose, C-reactive protein (CRP) and fibrinogen. FIT was measured by a Sci f-reported physical activity questionnaire and by a maximal treadmill exercise test, expressed in metabolic equivalents (METs). Results: Subjects in the highest FIT according to the treadmill test had significantly lower BMI, waist circumference, systolic and diastolic blood pressure, total cholesterol, triglycerides, glucose, CRP and fibrinogen, and higher HDL cholesterol (adjusted by age and gender). LDL cholesterol did not show significant changes. The same pattern of RF (including LDL cholesterol) and CRP was observed when using Sci f-reported physical activity as a FIT parameter There was a significant association between both methods to measure FIT (p <0.0001, Chi-square Mantel-Haenszel). Conclusions: Our findings show that a better level off IT, assessed by exercise testing or through Sci f report is associated with improved levels of traditional and emergent RF.

Relación entre capacidad aeróbica máxima, componentes del síndrome metabólico e inflamación subclínica en sujetos estudiados en una Unidad de Cardiología Preventiva Ambulatoria / Relationship between aerobic capacity, metabolic syndrome components and chronic subclinical inflammatory markers in subjects attending a primary prevention clinic

Antecedentes: El síndrome metabólico (SMET) está presente en uno de cada 4 sujetos en Chile. Existiría una relación directa entre el SMET y la inflamación subclínica crónica determinada por proteína C-reactiva ultrasensible (PCRus). La actividad física se asocia a un aumento en la sensibilidad a insulina y menor desarrollo de SMET y diabetes. Existe escasa información sobre la relación entre la actividad física, SMET y PCRus. Objetivos: Determinar la relación entre la capacidad aeróbica determinada por ergometría, los factores de riesgo del SMET y la inflamación subclínica en una población presuntamente sana. Métodos: Estudio prospectivo en una población estudiada en una unidad de cardiología preventiva ambulatoria entre noviembre de 2003 y agosto de 2005. En todos los sujetos se efectuó una evaluación sobre factores de riesgo cardiovascular, medición de IMC, cintura, cadera, perfil de lípidos, glicemia de ayuno, PCRus (desde marzo 2005), presión arterial sistólica y diastólica (PAS-PAD) en 2 días alternos, y test de esfuerzo máximo (frecuencia cardíaca alcanzada > 85 por ciento de la teórica o percepción de esfuerzo en escala de Borg > 17) medido en equivalentes metabólicos (METS). Resultados: Se estudiaron 1587 individuos (1016 hombres) de edad promedio 52 +/- 12 años. La mayoría (67 por ciento) tenía sobrepeso u obesidad, y un 25 por ciento cumplía con los criterios (ATP III) para SMET. Se demostró una correlación significativa entre la actividad física medida en METS con la edad (r= 0.57, p<0.001) y con algunos de los componentes del SMET como glicemia (r= - 0.16, p<0.001); HDL(r= -0.09, p<0.001) y PAS (r= -0.3, p<0.001). En la siguiente tabla se muestra la distribución de componentes del SMET y PCRus según cuartiles de actividad física: Los niveles de PCRus fueron significativamente menores en sujetos con SMET (+) y con mayor capacidad aeróbica versus los con menor...

Background: The metabolic syndrome (MS) is present in 1 out of 4 subjects in Chile. A direct relation between the presence of metabolic syndrome and chronic subclinical inflammation as revealed by ultra sensitive C reactive protein (CRP) has been postulated. Physical activity is associated with an increased insulin sensitivity and a lower incidence of MS and diabetes. There is limited information about the relation between physical activity, the MS and subclinical inflammation in healthy subjects. Aim: To determine the relationship between aerobic capacity measured by treadmill exercise testing, the components of MS and subclinical inflammation in a presumably healthy population. Methods: A prospective study was carried out in a primary prevention cardiac unit between november 2003 and august 2005. Risk factors for cardiovascular disease were evaluated. BMI, waist and hip circumference, fasting glucose, CRP, systolic and diastolic blood pressure were measured. METS were determined through an exercise test set to achieve 85 percent of maximal heart rate or a level 17 of Borg’s perceived effort. Results: 1587 subjects (1016 males) with mean age 52 years (SD 12) were studied. Most were overweight or obese: 25 percent met ATP III criteria for MS. METS were significantly correlated to age (r 0.57, p<0.001), fasting glucose level (r -0.16, p<0.001), HDL (r -0.09, p<0.001) and systolic BP (r -0.3, p<0.001). The distribution of mean values for MS components and CRP according to quartiles of METS is shown below: Conclusion: A strong association between aerobic capacity, MS factors and subclinical inflammation is shown in this study. It is postulated that exercise leading to improvement in aerobic capacity may have a beneficial effect upon chronic inflammation and cardiovascular risk.