Utilización de fármacos en niños en cuidados intensivos: estudio de las prescripciones off-label / Drug utilization pattern in children and off-label use of medicines in a pediatric intensive care unit

OBJETIVO: Evaluar los usos off-label (fuera de ficha técnica [FT]) y unlicensed (medicamentos no autorizados específicamente para niños) en cuidados intensivos neonatales y pediátricos. METODOLOGÍA: Se realizó un estudio transversal en la UCINP (Unidad de Cuidados Intensivos Neonatales y Pediátricos) de un hospital público de tercer nivel de Granada, incluyéndose a todos los niños en los que se indicara al menos un tratamiento farmacológico, mediante reclutamiento consecutivo, y durante un periodo de 5 meses (N = 81). Las variables recogidas fueron sociodemográficas, clínicas, y medicación. Todas las prescripciones fueron clasificadas a partir de la información contenida en FT sobre uso en niños. RESULTADOS: Hubo un total de 601 prescripciones, con una media de 7,4 ± 6 medicamentos por niño. Los fármacos más empleados pertenecían a los grupos J (antiinfecciosos), N (sistema nervioso) y C (cardiovascular). Algo más de la mitad de las prescripciones fueron off-label (52%), fundamentalmente por emplear una dosificación distinta de la recomendada en FT (79%), seguida de diferente indicación (13,5%), edad (5%) y vía de administración (2,5%). El uso de medicamentos no específicamente autorizados en niños solo supuso el 5% de las prescripciones. CONCLUSIONES: El presente estudio aporta datos sobre este tipo de prescripciones en una UCINP española. Pone de manifiesto que el 89% de los niños tiene al menos una prescripción fuera de FT y un 22,3% al menos un uso de fármaco no autorizado para niños. Cifras elevadas, pero justificables dentro del ámbito de unos cuidados intensivos que, además, incluyen neonatos. Pero aunque muchos de los tratamientos estén protocolizados, sería deseable mejorar la evidencia disponible, así como actualizar las FT

OBJECTIVE: This study aims to assess the prescription profile and license status of drugs used in a neonatal and pediatric intensive care unit (NPICU). METHODS: A prospective observational study was conducted on a dynamic cohort of children admitted to an NPICU (N = 81) in a tertiary hospital (Granada, Spain). All prescriptions were classified asoff-label or unlicensed based on the summary of product characteristics (SPC). RESULTS: Of a total of 601 prescriptions, the patients received a mean of 7.4 ± 6 drugs each. The most commonly prescribed drugs corresponded to classes J (anti-infectious, systemic use) N (nervous system) and C (cardiovascular). A little over one-half of the prescriptions were off-label (52%), usually due to dosages differing from the SPC recommendations (79%), followed by different indications (13.5%), age (5%) and administration route (2.5%). In this NPICU, unlicensed usage represented only 5% of all prescriptions. CONCLUSIONS: This study contributes data on prescription of this kind in a Spanish NPICU, revealing at least one off-label prescription in 89% of the children and at least one unlicensed use in 22.3%. These are high figures, but are to be expected given the inclusion of newborn infants and the critical care setting. Even though such usage follows clinical protocols, we underscore the dual need to base treatment on the best available evidence, and to upgrade the SPC accordingly

Drug utilization pattern in children and off-label use of medicines in a pediatric intensive care unit.

OBJECTIVE: This study aims to assess the prescription profile and license status of drugs used in a neonatal and pediatric intensive care unit (NPICU). METHODS: A prospective observational study was conducted on a dynamic cohort of children admitted to an NPICU (N=81) in a tertiary hospital (Granada, Spain). All prescriptions were classified as off-label or unlicensed based on the summary of product characteristics (SPC). RESULTS: Of a total of 601 prescriptions, the patients received a mean of 7.4 ± 6 drugs each. The most commonly prescribed drugs corresponded to classes J (anti-infectious, systemic use) N (nervous system) and C (cardiovascular). A little over one-half of the prescriptions were off-label (52%), usually due to dosages differing from the SPC recommendations (79%), followed by different indications (13.5%), age (5%) and administration route (2.5%). In this NPICU, unlicensed usage represented only 5% of all prescriptions. CONCLUSIONS: This study contributes data on prescription of this kind in a Spanish NPICU, revealing at least one off-label prescription in 89% of the children and at least one unlicensed use in 22.3%. These are high figures, but are to be expected given the inclusion of newborn infants and the critical care setting. Even though such usage follows clinical protocols, we underscore the dual need to base treatment on the best available evidence, and to upgrade the SPC accordingly.

Analysis of age-period-cohort effects on overall mortality in Andalusia (Southern Spain).

OBJECTIVES: To evaluate the age-period-cohort effects on overall mortality in Andalusia (Spain). STUDY DESIGN: An ecological study was implemented with a Lexis diagram triangle comprising each annual age group, year of death and year of birth as the unit of analysis. METHODS: In all 1,384,899 deaths from all causes were analysed for individuals between the ages of 1 and 84 years who died in Andalusia in the period 1981-2008. A non-linear regression model was estimated for each gender group and geographical area. The effects of age, year of death and birth cohort were parameterized using B-spline smoothing functions. RESULTS: There is a downward trend in mortality by age to around the age of 15 years, from which point the trend turned upwards. For cohorts born between 1945 and 1965, the rate climbed steadily. From 1965, the rate turned downwards. Death rates increased between 1995 and 2000, only to turn down again until the end of the period. Broadly, these results were similar for both men and women, in all the provinces of Andalusia and for Andalusia as a whole. CONCLUSIONS: This study points to an age-period-cohort effect on deaths from all causes in all the geographic areas studied.

Contribution of sociodemographic characteristics, occupation, diet and lifestyle to DDT and DDE concentrations in serum and adipose tissue from a Bolivian cohort.

The organochlorine pesticide p,p'-Dichlorodiphenyltrichloroethane (DDT) was widely used in the early 1960s-70s for vector control in tropical and subtropical areas of South America. Due to its persistence, DDT has a high potential to bioaccumulate in the food chain and living organisms and is a major public health concern, especially in South America. The main purpose of the present study was to investigate predictors of serum and adipose tissue concentrations of p,p'-DDT and its main metabolite, p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), in an adult cohort (n=112) from Santa Cruz de la Sierra, Bolivia, using multiple linear regression models. These models explained 29.3-47.8% of the variability in adipose tissue concentrations of p,p'-DDT and p,p'-DDE, respectively, and 32.9-47.0% of that in serum. Main exposure predictors included age, occupational class, residence, diet, smoking habit, and accumulated breastfeeding time. This is one of the few studies to explore predictors of human exposure to these chemicals using a multivariate approach in a South American population. Results show that predictors of human exposure to p,p'-DDT and p,p'-DDE in Santa Cruz de la Sierra may diverge from those found in other populations of the world, due to particular sociodemographic and lifestyle characteristics of this region.

Area deprivation and mortality in the provincial capital cities of Andalusia and Catalonia (Spain).

OBJECTIVE: To study the linkage between material deprivation and mortality from all causes, for men and women separately, in the capital cities of the provinces in Andalusia and Catalonia (Spain). METHODS: A small-area ecological study was devised using the census section as the unit for analysis. 188,983 Deaths occurring in the capital cities of the Andalusian provinces and 109,478 deaths recorded in the Catalan capital cities were examined. Principal components factorial analysis was used to devise a material deprivation index comprising the percentage of manual labourers, unemployment and illiteracy. A hierarchical Bayesian model was used to study the relationship between mortality and area deprivation. MAIN RESULTS: In most cities, results show an increased male mortality risk in the most deprived areas in relation to the least depressed. In Andalusia, the relative risks between the highest and lowest deprivation decile ranged from 1.24 (Malaga) to 1.40 (Granada), with 95% credibility intervals showing a significant excess risk. In Catalonia, relative risks ranged between 1.08 (Girona) and 1.50 (Tarragona). No evidence was found for an excess of female mortality in most deprived areas in either of the autonomous communities. CONCLUSIONS: Within cities, gender-related differences were revealed when deprivation was correlated geographically with mortality rates. These differences were found from an ecological perspective. Further research is needed in order to validate these results from an individual approach. The idea to be analysed is to identify those factors that explain these differences at an individual level.

Periodontitis as risk factor for acute myocardial infarction. A case control study of Spanish adults.

OBJECTIVE: The present study was designed to determine, in a case-control study of a Spanish population, whether periodontitis is a risk factor for acute myocardial infarction. BACKGROUND: Although part of cardiovascular risk could be explained by periodontal disease, available meta-analyses find significant heterogeneity and recommend the need for further observational and intervention studies. METHODS: A case-control study was conducted of 149 Spanish patients aged between 40 and 75 years, with 72 cases (acute myocardial infarction) and 77 controls (trauma patients). Periodontitis was measured as the percentage of sites with clinical attachment loss greater than 3 mm. A multivariate logistic regression model was constructed to estimate the adjusted effect of periodontitis on acute myocardial infarction, after considering the potential confounding effect of a large pool of risk factors. RESULTS: In a bivariate analysis, males, older patients, smokers, and those with hypertension, diabetes or hypercholesterolemia, showed an increased risk of acute myocardial infarction. The cases, compared to controls, showed worse results for all periodontal variables studied: gingival retraction, pocket depth, and periodontitis. The final multiple logistic model included sex, age, tobacco habit, hypertension, diabetes, hypercholesterolemia, regular exercise, and periodontitis. The association between periodontitis (dichotomized) and acute myocardial infarction was high and significant in both the unadjusted (odds ratio = 4.42, p < 0.001) and adjusted analyses (odds ratio = 3.31, p = 0.005). CONCLUSION: There is evidence of an association between periodontitis and acute myocardial infarction after adjusting for well-known risk factors for acute myocardial infarction.

[Efficacy of time series analysis in health planning for cancer in Spain]. / Eficacia del análisis de series temporales para la planificación sanitaria del cáncer en España.

OBJECTIVE: To evaluate the accuracy of the time series model used to forecast cancer mortality rates in Spain published in Atención Primaria for the year 2000. DESIGN: Descriptive study. SETTING: Spain. PARTICIPANTS: All cancer deaths recorded in Spain during the year 2000. MAIN MEASUREMENTS: The forecast for cancer mortality rates in males and females for the year 2000 was obtained from a paper published in 1999 in the journal Atención Primaria. Official data on cancer mortality rates for the year 2000 were obtained from the Spanish Statistical Office (INE) in 2003. RESULTS: In 2000, 59,212 males and 35,860 females died of cancer. The figures predicted by the time series model were 60,561 for males and 36,183 for females. Thus, the actual cancer mortality figures published by the Statistical Office fell within the confidence intervals of the forecasts for both gross mortality and cancer deaths. CONCLUSIONS: The difference between the true cancer mortality rate and the forecast is very small and not significant for health planning. Time series analysis is highly effective as a basis for decision-taking in cancer health planning. Cancer health policy and management can also benefit from the strength of these models.

Eficacia del análisis de series temporales para la planificación sanitaria del cáncer en España / Efficacy of time series analysis in health planning for cancer in Spain

Objetivo. Evaluar la eficacia del modelo utilizado para predecir la mortalidad por cáncer en España para el año 2000, cuyas estimaciones aparecieron en la revista ATENCIÓN PRIMARIA en 1999.Diseño. Estudio descriptivo. Emplazamiento. Ámbito nacional. Participantes. Defunciones por cáncer ocurridas en España durante el año 2000.Mediciones principales. Las predicciones realizadas para el año 2000 para varones y mujeres se obtuvieron de la publicación aparecida en ATENCIÓN PRIMARIA en el año 1999.Los datos oficiales de mortalidad por cáncer para el año 2000 se tomaron de las defunciones según la causa de muerte publicadas por el Instituto Nacional de Estadística (INE) a comienzos de 2003.Resultados. En el año 2000, 59.212 varones y 35.860 mujeres murieron por cáncer, según las cifras oficiales publicadas por el INE. Las cifras predichas para ese año por los modelos de series temporales fueron de 60.561 varones y 36.183 mujeres. Las predicciones realizadas para el año 2000 dieron intervalos de confianza para la tasa bruta de mortalidad y el número de defunciones por cáncer en España que contenían las verdaderas cifras publicadas por el INE en 2003.Conclusiones. El error global cometido en las predicciones de la mortalidad por cáncer en España para el año 2000 es casi despreciable para el proceso de la planificación sanitaria, siendo métodos altamente eficaces para la toma de decisiones. El análisis de series temporales no sólo puede realizar importantes aportaciones en la planificación sanitaria del cáncer. También la gestión y política sanitaria pueden beneficiarse de la potencia de estos modelos (AU)

[Changes in mortality associated with traffic accidents in Andalusia from 1975 to 2001 and forecast for 2004]. / Evolución de la mortalidad por accidentes de tráfico en Andalucía desde 1975 hasta 2001 y predicción.

OBJECTIVE: To describe the evolution of mortality due to traffic accidents in Andalusia between 1975 and 2001 and to predict the mortality rates for 2004. DESIGN: Ecological study with a population base. SETTING: Residents in Andalusia between 1975 and 2001. PARTICIPANTS: Deaths due to traffic accidents in Andalusia between 1975 and 2001. Main measurements and results. Mortality rates adjusted for age in men and women and in three groups: under-35s, from 35 to 64, and over 64. The evolution of rates over time was studied through trend analysis. Short-term predictions of the mortality rates were made. The adjusted rates for men fell from 21.20 per 100000 inhabitants in 2001 to 20.21 in 2001. The rate for women fell from 4.87 to 4.60 during the same period. The evolution of mortality was similar for both sexes. CONCLUSIONS: Traffic accident mortality evolved in an oscillating way, with an important fall in numbers starting in 1989. Mortality rates increased with age. The predictions formulated indicate that the stable trend starting in 1995 will remain the same in the coming years.

Population-based study of cutaneous malignant melanoma in the Granada province (Spain), 1985-1992.

Cutaneous melanoma has received substantial attention during the last years because of the increase in its incidence which has been registered in many countries. This paper aims at describing the incidence and characteristics of all new cutaneous malignant melanoma cases during 1985-1992 reported to the Granada Cancer Registry (Spain) in the context of Mediterranean populations. A population-based study with 247 cutaneous melanoma cases was carried out. The variables used were: sex, age, anatomic site, hystological type, level of invasion and tumour thickness. The Age-Standardised incidence Rate per World population (ASRW) was 2.9 for males and 3.7 for females in the whole period. An increasing incidence trend for both males and females was found. The ASRW in 1985-1987, 1988-1990 and 1991-1992 was respectively 2.2, 2.9 and 3.2 for males and 3, 3.4, 4.7 for females. The most frequent location was trunk for males (36%) and lower extremities for females (44%). The most frequent hystological type for both males and females was superficial spreading melanoma. Seventy-six percent of males and 60% of females were diagnosed Clark's level III or over. Average tumour thickness was 3.3 mm for males and 2.4 mm for females. The results of this study can be a guidance for the setting up of health policies which would contribute to the prevention of the disease and to an improvement in care. Because of the increase in incidence rates and the high percentage of cases which were diagnosed at advanced stages, it is advised that prevention campaigns are addressed to the Granada population.

[Multilevel models or the importance of ranking]. / Los modelos multinivel o la importancia de la jerarquía.

Many researchers in Public Health have data bases with a hierarchical structure. The studied patients (level 1) can be nested in groups, i.e., district, doctor, hospital, etc. (level 2). It is possible that patients in the same group be similar, so traditional regression models can not be used because the hypothesis of independent observations is not satisfied. A Multilevel Analysis, using hierarchical models, can be a solution for this problem; these models take into account the distribution of the data at different levels to estimate two types of variability: one due to individuals in the study and another due to the groups in which patients are nested. These types of models were applied in education in the last decade, however they have been recently applied in Health Research. This paper is a review about multilevel analysis. A discussion about hierarchichal models versus traditional regression models is presented and some applications in Epidemiology and Health Research are showed.

[The short-term effects of air pollution on mortality. The results of the EMCAM project in the city of Seville, 1992-1996. Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad]. / Efectos a corto plazo de la contaminación atmosférica sobre la mortalidad. Resultados del proyecto EMECAM en la ciudad de Sevilla, 1992-1996

BACKGROUND: As part of the EMECAM Project, the objective of this study is that of assessing the impact of air pollution on the daily mortality in Seville throughout the 1992-1996 period. METHODS: During the 1992-1996 period, readings were taken daily of the amounts of SO2, particles in suspension (PM10) and NO2 present in the air in the city of Seville, in addition to the number of deaths daily due to different causes. For analyzing this data, a multivariable Poisson regression model was used for modeling each one of the causes of death in terms of the air immission readings, controlling other confusion-causing variables. RESULTS: A relationship was found to exist between the rises in the NO2 levels and the daily death rate throughout the months of May to October. For each 10 micrograms/m3 rise, the risk of death or all causes showed a 2% rise, the same rise in the NO2 levels leading to a 3% rise in the risk of death resulting from cardiovascular diseases. CONCLUSIONS: A relationship exists between the levels of NO2 air pollution and the daily death rate in Seville. The findings provide scientific knowledge and information which can be of use for preventing the impact of air pollution on human health.

[The short-term effects of air pollution on mortality: the results of the EMECAM project in the city of Huelva, 1993-96. Estudio Multicéntrico Español sobre la Relación entre la Contaminación Atmosférica y la Mortalidad]. / Efectos a corto plazo de la contaminación atmosférica sobre la mortalidad: resultados del proyecto EMECAM en la ciudad de Huelva, 1993-96.

BACKGROUND: The objective of this study was to estimate the relationship between the levels of air pollution and the daily mortality in the city of Huelva for the 1993-1996 period using the EMECAM methodology. METHODS: The number of daily deaths for all causes except external ones, the death rate of those over age 69, due to diseases of the circulatory system and for respiratory diseases were used as rate indicators. Four pollutants--SO2, PM10, NO2 and CO--were analyzed, the daily levels of which were furnished by the air pollution monitoring network in Huelva. Autoregressive Poisson regression models were constructed controlling by tendency, seasonality, temperature, humidity, flue and events out of the ordinary. RESULTS: For the mortality rate for all causes, a significant association impact was found to exist for the NO2 for the entire period (RR10 microgram/m3: 1.0414; CI95%: 1.0047-1.0794) and for the particles (PM10) for the cold half of the year (RR10 microgram/m3: 1.0358; CI95%: 1.007-1.0722). For the mortality in people over age 69, a significant relationship was found to exist for SO2 throughout the entire period (RR10 microgram/m3: 1.0606; CI95%: 1.0020-1.1227). A significant relationship to the mortality from respiratory disease particles (PM10) was found to exist for the cold half of the year (RR10 microgram/m3: 1.1412; IC95%: 1.0300-1.2644). There was no association of contaminants with cardiovascular mortality; also there was no association between levels of CO and mortality indicators. CONCLUSIONS: In Huelva, significant relationships have been found to exist between the current levels of air pollution resulting from particles, SO2 and NO2 and the daily mortality. The impact of these pollutants on the mortality is coherent with scientific literature, although in the case of Huelva, the extremely small number of daily deaths due to its small population and other factors limit the consistency thereof.

[The prediction of the cancer incidence and mortality rates in Spain for the year 2000]. / Predicción de las tasas de incidencia y mortalidad por cáncer en España para el año 2000.

OBJECTIVE: To forecast the cancer incidence and mortality rates in Spain for the year 2000, and to estimate the number of new cases and the number of dead patients due to the cancer for this year. DESIGN: Ecological study with time series analysis. PATIENTS: Cancer mortality rates in Spain was obtained from 1905 to 1995. MEASUREMENTS AND RESULTS: Brow method was applied in order to forecast cancer mortality rates for the year 2000. An estimation of the incidence rates in Spain was obtained from the incidence/mortality rate (1.49 for males and 2.07 for females), given by the International Agency for Research on Cancer (IARC). INE's publications were used in order to estimate the number of new cases and the number of dead patients due to the cancer for the year 2000. The forecasting about cancer mortality rates in Spain for the year 2000 were 312.93 in men and 180.56 in women. An increasing in mortality will be produced in the following years. 90,000 men and 75,000 women will be diagnosed with cancer; 61,000 men and 36,000 women will be died due of this disease. CONCLUSION: The trends in cancer incidence and mortality are increasing. These results could be interesting in health policy in order to plan different actions in the future.

[Update on regression: softening relationships]. / Actualizaciones en regresión: suavizando las relaciones.

A frequently used methodology for the analysis of different kinds of health problems is based on regression models: lineal, logistic, etc.; these models depend on a set of parameters that must be estimated from the data. However, they present the drawback of being very rigid since, occasionally, they impose overly strict relations between the variables. Non-parametric regression methods present the advantage of not establishing a priori restrictions, allowing the data to indicates us the appropriate functional form. In this paper several modern non-parametric regression methods are presented that in addition to their usefulness per se can prone to be of invaluable help in the diagnostic process for parametric regression methods. The current availability of the necessary software should contribute to their increased use which, in turn, will probably lead to an improved understanding of the health problems under study.