Vitamina B12: ¿para algo más que el tratamiento de la anemia megaloblástica? / Vitamin B12: For more than just the treatment of megaloblastic anemia?

Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins and is ingested through food of animal origin such as eggs, milk, red meat and poultry, fish, and shellfish. Its clinical indication is the treatment of hypovitaminosis B12 administered orally or intramuscularly in the form of hydroxocobalamin. Hypovitaminosis B12 is mainly caused by deficient dietary intake (individuals with malnutrition, vegetarians or vegans, older adults, pregnant people, individuals with alcohol use disorder); when intestinal absorption is reduced (atrophic gastritis, malabsorption syndrome, gastrointestinal surgery); and for causes associated with the intake of drugs (antacids, metformin). Hypervitaminosis B12 has been associated with renal failure; liver diseases such as cirrhosis and acute-phase hepatitis; alcohol use disorder with or without liver involvement; solid tumors of the lung, liver, esophagus, pancreas, and colorectum; and in hematological malignancies such as leukemia and bone marrow dysplasia (AU)

La vitamina B12 o cobalamina pertenece al grupo de vitaminas hidrosolubles y su aporte se realiza a través de la ingesta de alimentos de origen animal como huevo; leche; carnes rojas y de aves; pescados y mariscos. Su indicación clínica es el tratamiento de la hipovitaminosis B12 administrada por vía oral o intramuscular en forma de hidroxicobalamina. La hipovitaminosis B12 se origina, principalmente, por un déficit de aporte en la dieta (malnutrición, sujetos vegetarianos o veganos, ancianos, embarazo, alcoholismo); cuando está disminuida su absorción intestinal (gastritis atrófica, síndrome de malabsorción intestinal, cirugía gastro-intestinal) y asociada a ingesta de fármacos (antiácidos, metformina). La hipervitaminosis B12 se ha relacionado con la insuficiencia renal; hepatopatías como cirrosis y hepatitis en fase aguda; alcoholismo con o sin afectación hepática; tumores sólidos de pulmón, hígado, esófago, páncreas y colorrectal y en neoplasias hematológicas como leucemia y la displasia medular (AU)

Vitamin B12: For more than just the treatment of megaloblastic anemia?

Vitamin B12, or cobalamin, belongs to the group of water-soluble vitamins and is ingested through food of animal origin such as eggs, milk, red meat and poultry, fish, and shellfish. Its clinical indication is the treatment of hypovitaminosis B12 administered orally or intramuscularly in the form of hydroxocobalamin. Hypovitaminosis B12 is mainly caused by deficient dietary intake (individuals with malnutrition, vegetarians or vegans, older adults, pregnant people, individuals with alcohol use disorder); when intestinal absorption is reduced (atrophic gastritis, malabsorption syndrome, gastrointestinal surgery); and for causes associated with the intake of drugs (antacids, metformin). Hypervitaminosis B12 has been associated with renal failure; liver diseases such as cirrhosis and acute-phase hepatitis; alcohol use disorder with or without liver involvement; solid tumors of the lung, liver, esophagus, pancreas, and colorectum; and in hematological malignancies such as leukemia and bone marrow dysplasia.

Mortalidad hospitalaria asociada a medicamentos en un Servicio de Medicina Interna / Drug-related mortality among inpatients admitted in Internal Medicine

Fundamento: Analizar la mortalidad asociada a fármacos, los medicamentos más implicados y los factores de riesgo asociados en pacientes ingresados en Medicina Interna. Material y métodos: Estudio retrospectivo, observacional. Se revisaron las historias clínicas de los adultos fallecidos consecutivamente en el servicio de Medicina Interna de un hospital universitario durante veintidós meses. La variable principal fue la mortalidad hospitalaria sospechosa de estar relacionada con medicamentos administrados durante el ingreso. Resultados: De las 455 muertes analizadas, el 22,2% estuvieron relacionadas con los medicamentos recibidos; en 55 casos (12,1%) los medicamentos fueron considerados sospechosos de ser la causa de la muerte y en 46 casos (10,1%) de contribuir a ello. Los diagnósticos más frecuentes en los casos de muerte asociada a medicamentos fueron arritmia cardiaca (23,7%), hemorragia grave (19,8%) y neumonía aspirativa (12,8%). Los medicamentos implicados con mayor prevalencia en las muertes relacionadas con el tratamiento farmacológico fueron los antitrombóticos (23,7 %), la digoxina (21,7 %), los antipsicóticos (17,8%) y las benzodiacepinas (14,8%). El único factor de riesgo independiente de mortalidad asociada a tratamiento fue el número de medicamentos administrados (OR=1,25; IC95%: 1,14-1,37). No se encontró asociación significativa con la edad, sexo, número de patologías o duración de la estancia hospitalaria. Conclusiones: Un alto porcentaje de las muertes de pacientes ingresados en Medicina Interna se consideran relacionadas con los medicamentos recibidos. Los antitrombóticos, digoxina y psicofármacos fueron los agentes más frecuentemente implicados. Dicha mortalidad se asocia de manera independiente y significativa con el número de medicamentos administrados

Background: To analyze the mortality associated with prescriptions, the drugs most frequently involved and the associated risk factors in patients admitted to Internal Medicine. Methods: A retrospective, observational study. The clinical records of adult patients who died consecutively in the department of Internal Medicine in a Spanish tertiary hospital over twenty-two months were reviewed. The main variable was the prevalence of hospital death suspected of being related to the medications administered during admission. Results: Out of the 455 deaths analyzed, 22.2% were related to the medications received; in 55 cases (12.1%) the drugs were suspected of being the cause of death and in 46 cases (10.1%) of contributing to it. The most frequent diagnoses in cases of death associated with drugs were cardiac arrhythmia (23.7%), severe hemorrhage (19.8%) and aspiration pneumonia (12.8%). The drugs with the highest prevalence in deaths related to pharmacological treatment were antithrombotic drugs (23.7%), digoxin (21.7%), antipsychotics (17.8%) and benzodiazepines (14.8%). The only independent risk factor for mortality associated with treatment was the number of medications administered (OR=1.25, 95%CI: 1.14-1.37). No significant association was found with age, sex, number of pathologies or duration of hospital stay. Conclusion: A high percentage of deaths of patients admitted to Internal Medicine were considered related to the medications received. Antithrombotic drugs, digoxin and psychotropic drugs were the agents most frequently implicated. This mortality is independently and significantly associated with the number of medications administered

[Drug-related mortality among inpatients admitted in Internal Medicine]. / Mortalidad hospitalaria asociada a medicamentos en un Servicio de Medicina Interna.

BACKGROUND: To analyze the mortality associated with prescriptions, the drugs most frequently involved and the associated risk factors in patients admitted to Internal Medicine. METHODS: A retrospective, observational study. The clinical records of adult patients who died consecutively in the department of Internal Medicine in a Spanish tertiary hospital over twenty-two months were reviewed. The main variable was the prevalence of hospital death suspected of being related to the medications administered during admission. RESULTS: Out of the 455 deaths analyzed, 22.2% were related to the medications received; in 55 cases (12.1%) the drugs were suspected of being the cause of death and in 46 cases (10.1%) of contributing to it. The most frequent diagnoses in cases of death associated with drugs were cardiac arrhythmia (23.7%), severe hemorrhage (19.8%) and aspiration pneumonia (12.8%). The drugs with the highest prevalence in deaths related to pharmacological treatment were an-tithrombotic drugs (23.7%), digoxin (21.7%), antipsychotics (17.8%) and benzodiazepines (14.8%). The only independent risk factor for mortality associated with treatment was the number of medications administered (OR=1.25, 95%CI: 1.14-1.37). No significant association was found with age, sex, number of pathologies or duration of hospital stay. CONCLUSION: A high percentage of deaths of patients admitted to Internal Medicine were considered related to the medications received. Antithrombotic drugs, digoxin and psychotropic drugs were the agents most frequently implicated. This mortality is independently and significantly associated with the number of medications administered.

Prevalence of fatal adverse drug reactions in hospitalized patients.

OBJECTIVE: The aims of the present study were to assess the prevalence of fatal adverse drug reactions (FADRs) in a hospitalized population, identify the drugs involved and investigate reported risk factors for these events. METHODS: The study population of this retrospective, single-centre case study comprised 289 patients dying between 1 January 2004 and 31 December 2004 and registered in the Cause of Death Register of a teaching hospital. All compiled data were recorded by two observers especially trained to identify and report adverse drug reactions (ADRs). The degree of probability that the ADR led directly to death was determined by using WHO criteria and an adapted version of Naranjo's score. RESULTS: Among 289 deceased study subjects, 17 (5.9%) were suspected to have died from an ADR. The most common suspected FADRs were gastrointestinal hemorrhages (52.9%), central nervous system hemorrhages (17.6%), cardiac disorders (17.6%), drug-induced myelosuppression (6%) and antimicrobial-related enterocolitis (6%). The drugs most frequently implicated in a FADR were antithrombotic drugs (65%), nonsteroidal anti-inflammatory drugs (NSAIDs) (47%) and corticosteroids (29%). The only risk factors associated with FADRs in this population were multiple-drug therapy and the presence of platelet antiaggregants and NSAIDs, alone or associated. CONCLUSIONS: FADRs are an important cause of death in hospitalized patients. Hemorrhages were seen in a majority of the fatal reactions, and antithrombotic agents or NSAIDs were implicated in most of these events.

Reacciones adversas a medicamentos en pacientes que acudieron a un hospital general: un meta-análisis de resultados / Adverse drug reactions in patients visiting a general hospital: a meta-analysis of results

Objetivos: El propósito del estudio es presentar los resultados de un meta-análisis sobre las reacciones adversas a medicamentos (RAM) en pacientes ingresados y que acudieron al servicio de urgencia de un hospital general en los últimos veinte años. Pacientes y métodos: Se hizo una revisión exhaustiva de artículos publicados entre 1985-06, ambos inclusive, en el IME (Índice Médico Español) y MEDLINE eligiendo de forma rigurosa doce de treinta publicaciones, tras aplicar criterios de inclusión y exclusión. Se requirió información sobre sintomatología, pronóstico, tipo, fármacos implicados, imputabilidad, e ingresos por RA; los factores asociados a su aparición como la edad, sexo, número de fármacos, la historia previa de RAM, método empleado para detectar las RAM, y duración del estudio. Como método estadístico para el meta-análisis usamos el de efectos aleatorios de DerSimonian y Laird, y como programa el STATA 9.1. Resultados: La estimación conjunta de RAM en pacientes españoles fue del 13% (IC95%); graves el 12% (IC95%); mortales el 0,1% (IC95%); fueron ciertas el 36% (IC95%); probables el 49,6% (IC95%); del tipo A el 71% (IC95%). Se hospitalizaron procedentes de urgencias por RAM el 5,1% (IC95%). No pudimos establecer una asociación con la comorbilidad, el nº de prescripciones y con la historia previa, pero si con la edad avanzada y el sexo femenino. Los sistemas más afectados por RAM fueron digestivo, piel, sistema nervioso, y cardiovascular. Entre los fármacos más implicados AINE, digoxina, IECA, antagonistas del calcio, furosemida, metamizol i.v, antidiabéticos, benzodiacepinas, broncodilatadores adrenérgicos, y antisicóticos clásicos. Conclusiones: Las RAM son un problema médico y económico importante con aspectos por definir. Se requieren mayores esfuerzos tanto para unificar criterios de publicación de resultados en estudios observacionales sobre RAM, como precisar el papel desempeñado por algunos factores asociados a su aparición caso del sexo, la historia previa y la comorbilidad (AU)

Objectives: The aim of this study was to present the results of a meta-analysis on adverse drug reactions (ADR) in spanish patients admitted to hospital and presenting to emergency department over the past 20 years. Patients and methods: An exhaustive review was undertaken of relevant articles in the IME (Spanish Medical Index) and MEDLINE databases and published between 1985 and 2006, rigorously selecting 12 out of 30 publications after applying inclusion and exclusion criteria. Information was required on: symptomatology, prognosis, type, drugs involved, imputability and admissions for ADR; and factors associated with ADR on set, e.g., age, sex, number of drugs, previous history of ADR, method used for ADR detection, and length of study period. A random-effects model (DerSimonian and Laird) and the STATA 9.1 programme were used for the meta-analysis. Results: The combined estimation of the percentage of Spanish patients with ADR was 13% (95% CI); with severe ADR, 12 % (95% CI) and with fatal ADR, 0.1% (95% CI). ADR diagnosis was definite in 36% (95% CI), probable in 49.6% (95% CI), and type A in 71% (95% CI) of cases. Among patients in the Emergency Department for ADR, 5.1%(95% IC) were hospitalized. No association was found with number of prescriptions or previous history. Association was established with advanced age and female sex. Digestive, skin, nervous and cardiovascular systems were those most affected by ADR. The drugs most frequently implicated included NSAIDs, digoxin, IACE, calcium antagonists, furosemide, i.v. metamizol, antidiabetics, benzodiazepines, adrenergic bronchodilators and classic antipsychotics. Conclusions: ADRs constitute a major medical and economic problem with aspects that have yet to be defined. Greater efforts are warranted to unify criteria for the publication of results in observational studies on ARD and to determine the role played by some factors associated with their on set, e.g., sex, previous history and comorbidities (AU)

[Adverse drug reactions in patients visiting a general hospital: a meta-analysis of results]. / Reacciones adversas a medicamentos en pacientes que acudieron a un hospital general: un meta-análisis de resultados.

OBJECTIVES: The aim of this study was to present the results of a meta-analysis on adverse drug reactions (ADR) in spanish patients admitted to hospital and presenting to emergency department over the past 20 years. PATIENTS AND METHODS: An exhaustive review was undertaken of relevant articles in the IME (Spanish Medical Index) and MEDLINE databases and published between 1985 and 2006, rigorously selecting 12 out of 30 publications after applying inclusion and exclusion criteria. Information was required on: symptomatology, prognosis, type, drugs involved, imputability and admissions for ADR; and factors associated with ADR onset, e.g., age, sex, number of drugs, previous history of ADR, method used for ADR detection, and length of study period. A random-effects model (DerSimonian and Laird) and the STATA 9.1 programme were used for the meta-analysis. RESULTS: The combined estimation of the percentage of Spanish patients with ADR was 13% (95% CI); with severe ADR, 12 % (95% CI) and with fatal ADR, 0.1% (95% CI). ADR diagnosis was definite in 36% (95% CI), probable in 49.6% (95% CI), and type A in 71% (95% CI) of cases. Among patients in the Emergency Department for ADR, 5.1% (95% IC) were hospitalized. No association was found with number of prescriptions or previous history. Association was established with advanced age and female sex. Digestive, skin, nervous and cardiovascular systems were those most affected by ADR. The drugs most frequently implicated included NSAIDs, digoxin, IACE, calcium antagonists, furosemide, i.v. metamizol, antidiabetics, benzodiazepines, adrenergic bronchodilators and classic antipsychotics. CONCLUSIONS: ADRs constitute a major medical and economic problem with aspects that have yet to be defined. Greater efforts are warranted to unify criteria for the publication of results in observational studies on ARD and to determine the role played by some factors associated with their onset, e.g., sex, previous history and comorbidities.

[Adverse drug reactions: an update review of the problem in Spain]. / Reacciones adversas a medicamentos: una revisión actualizada del problema en España.

Adverse drug reactions (ADR) are an important clinical problem and their impact on the Spanish population is unknown. The aim of this study was to provide an overview of ADR based on a review of observational studies published in Spain since 1974. Twenty-seven studies of Spanish patients were selected from a total of 90 articles published in national and international journals between 1974 and 2004. Studies eligible for inclusion were identified with an especially designed checklist. The incidence of ADR among 139,799 patients was 3%; 0.6% of the events led to death, and 17% led to severe illness. Two-thirds (67%) of the ADR were classified as type A. The rate of hospitalization for ADR was 6.5%, and mean length stay was 4 +/- 1.3 days. Thirteen percent of the ADR were considered confirmed, and 57% were considered probable. Half (50%) of the ADR were considered preventable. The groups of medications involved most frequently were antibacterial, NSAID, psychoactive medications, bronchodilators, digoxin, non-opiate analgesics, vasodilators, antidiabetics and loop diuretics. The organs and systems involved most frequently were the digestive tract, skin, central nervous system, cardiovascular, endocrine and respiratory systems. The factors associated most strongly with ADR were advanced age and use of multiple medications. The relationships of gender, previous history of ADR and comorbidity with the incidence of ADR have yet to be established. This review of ADR provides useful information on the incidence of ADR in the Spanish population and serves as a baseline for future studies.

Reacciones adversas a medicamentos: una revisión actualizada del problema en España / Adverse drug reactions: an update review of the problem in Spain

Las reacciones adversas a medicamentos (RAM) son un problema clínico importante del que desconocemos su impacto en los enfermos españoles. En un intento por conocerlo se han seleccionado veintisiete estudios de RAM en pacientes españoles en un total de noventa artículos publicados en revistas nacionales e internacionales entre 1974-2004.En 139.799 pacientes se halló una incidencia del 3% de RAM con una mortalidad del 0,6% y un 17% de graves. Un 67% fueron del tipo A. La hospitalización por RAM fue del 6,5% con una estancia media de 4 ± 1,3 días. Un 13% fueron ciertas y un 57% probables. Un 50% de las RAM fueron previsibles y evitables. Los fármacos más implicados fueron antibacterianos, antiinflamatorios no esteroideos (AINE), psicofármacos, broncodilatadores, digoxina, analgésicos no opiáceos, vasodilatadores, antidiabéticos y diuréticos de asa. Los órganos y sistemas más afectados fueron digestivo, piel, sistema nervioso central (SNC), cardiovascular, endocrino y respiratorio. Los factores más fuertemente asociados con las RAM fueron la edad avanzada y la polimedicación. El sexo, la historia previa y la comorbilidad están por definir. Destacamos la importancia de los estudios sobre las RAM y la utilidad de esta revisión para futuras publicaciones sobre el tema

Adverse drug reactions (ADR) are an important clinical problem and their impact on the Spanish population is unknown. The aim of this study was to provide an overview of ADR based on a review of observational studies published in Spain since 1974. Twenty-seven studies of Spanish patients were selected from a total of 90 articles published in national and international journals between 1974 and 2004. Studies eligible for inclusion were identified with an especially designed checklist. The incidence of ADR among 139,799 patients was 3%; 0.6% of the events led to death, and 17% led to severe illness. Two-thirds (67%) of the ADR were classified as type A. The rate of hospitalization for ADR was 6.5%, and mean length stay was 4 ± 1.3 days. Thirteen percent of the ADR were considered confirmed, and 57% were considered probable. Half (50%) of the ADR were considered preventable. The groups of medications involved most frequently were antibacterial, NSAID, psychoactive medications, bronchodilators, digoxin, non-opiate analgesics, vasodilators, antidiabetics and loop diuretics. The organs and systems involved most frequently werethe digestive tract, skin, central nervous system, cardiovascular, endocrine and respiratory systems. The factors associated most strongly with ADR were advanced age and use of multiple medications. The relationships of gender, previous history of ADR and comorbidity with the incidence of ADR have yet to be established. This review of ADR provides useful information on the incidence of ADR in the Spanish population and serves as a baseline for future studies

Niveles inapropiados de digoxina en sangre relativos a 2.849 pacientes procedentes de un hospital universitario: influencia de la edad y el sexo / Inappropriate blood levels of digoxin in a study of 2,846 patients from a teaching hospital: the influence of age and sex

Objetivos: Detectar el porcentaje de pacientes con niveles inapropiados de digoxina en una amplia muestra y la posible influencia de la edad (mayores o menores de 65 años), y el sexo. Pacientes y método: Para ello hicimos un estudio retrospectivo sobre las concentraciones de digoxina en sangre de pacientes adultos con insuficiencia cardíaca congestiva y/o fibrilación auricular procedentes del Hospital Universitario San Cecilio entre los años 1992-2002. El análisis estadístico consistió en un análisis descriptivo saeguido de un test de la chi cuadrado para el cálculo de las diferencias entre las distintas variables. Resultados: Sobre un total de 5.623 determinaciones analíticas y 2.849 pacientes se detectó un 55,4 por ciento de pacientes con niveles de digoxina en sangre inapropiados. Los niveles inapropiados de digoxina fueron significativamente mayores en el grupo de mujeres frente a los varones (p < 0,001). Un 23 por ciento de pacientes tuvieron niveles elevados de digoxina en sangre (2 o más ng/ml) y un 16 por ciento con niveles muy bajos (0,5 ng/ml o menos). El promedio de determinaciones analíticas de digoxina en sangre por paciente fue de dos a lo largo del período estudiado. Conclusiones: Las mujeres y los ancianos tuvieron mayores porcentajes de concentraciones inapropiadas de digoxina en sangre, siendo las mujeres más proclives a tener tasas inapropiadas y elevadas. La monitorización terapéutica de digoxina en sangre no se utiliza todo lo frecuentemente que se debiera, llevando implícito un mal control del paciente digitalizado. Resaltamos el interés de este tipo de estudios (AU)

[Inappropriate blood levels of digoxin in a study of 2,849 patients from a teaching hospital: the influence of age and sex]. / Niveles inapropiados de digoxina en sangre relativos a 2.849 pacientes procedentes de un hospital universitario: influencia de la edad y el sexo.

OBJECTIVES: Digoxin is used to treat congestive heart failure and atrial fibrillation. Blood levels need to be monitored to optimize therapeutic performance, detect noncompliance and reduce toxicity. The aim of this study was to evaluate the use of digoxin by measuring blood levels of this drug. The influence of sex and age were also considered. PATIENTS AND METHOD: A retrospective study reviewed determinations of blood digoxin concentration in hospitalized and ambulatory patients with congestive heart failure, atrial fibrillation, or both, seen at the University of Granada Teaching Hospital (Spain) from 1992 to 2002. A chi square test was applied to results. RESULTS: A total of 5,623 laboratory tests for digoxin were done for 2,849 adult patients. Patients whose medical record was incomplete were excluded, and the final sample consisted of 2,629 patients. The 55.4% had inappropriate blood levels of digoxin. Inappropriate concentrations to digoxin were significantly higher in women (p < 0.001). The percentage of patients with high levels of the drug was significantly greater among men (p < 0.001). Very low concentrations (< 0.5 ng/ml) were found in 16% of the patients, with no significant difference between sexes. CONCLUSIONS: We detect a large percentage of older patients with inappropriate levels of digoxin in blood. Women were more likely than men to have high levels to digoxin in blood. There is evidence that therapeutic monitoring of blood levels of digoxin is not done as often as is advisable; this has implications for the care of patients being treated with this drug.

[Adverse reactions caused by drugs in pediatrics]. / Reacciones adversas causadas por medicamentos en pediatría.

The present study describes the results obtained in a screening program aimed at detecting adverse reactions to medication in children aged 1-8 years admitted to the Pediatrics Service of the University of Granada Hospital (Spain). The program is based on monitoring the patients for a period of 12 months. Of a total of 597 patients, adverse reactions were recorded in 4.4%. Within this group the reactions were classified as confirmed in 33.3%, probable in 30% and possible in 36.6%. Based on organs and systems, the CNS was most frequently affected (40%), followed in decreasing order by the digestive (37%) and cardiovascular systems (10%), skin (10%) and endocrine system (3%). The drugs most frequently involved were bronchodilators (40%), antibiotics (30%) and antiepileptics (20%). Among risk factors, polytherapy, hospitalization time and type of drug administered were the most important.