RESUMEN
INTRODUCTION: The use of unlicensed drugs is an unsettling issue in medical circles. "Dear Doctor Letters", batch recalls and important notifications about them are not provided systematically. Unlicensed use is, however, sometimes the only promising option for further medical treatment. Approaches to improve vigilance of pharmaceutical agents are available in many countries. An outline of legislation on and experiences with unlicensed use in selected industrial countries is reviewed in this article. Research data, documentation and assessment of the legal status of unlicensed drugs in selected industrial countries were obtained and compared to the situation in Germany. Expert interviews with specifically recruited representative samples from academic centers as well as regulatory and industrial sources, health technology assessments and health insurance data were analysed (N = 44, t = 20-120 min, transcribed verbatim). Approaches and limitations of licensing in different countries compared: Granting of a license has been an obligatory condition and there has been a duty of disclosure (sometimes with the right of prohibition) as well as reservations on the granting of permission. Central administration of data has made it possible to quantify and identify required drugs and ensure surveillance of their use. High administrative costs involved in giving notice of approval has caused delays in patient care. Procedures by which a medical doctor has to obtain permission affect physicians' freedom of action. Unlicensed and off-label use is variably regulated across the analysed settings. Legislation and regulation continue to be highly heterogeneous. Most promising approaches include the duty of disclosure, which allows quantification of use and surveillance of safety, including the right of recall while ensuring doctors' freedom to treat with medicinal products.
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Legislación de Medicamentos , Austria , Aprobación de Drogas , Drogas en Investigación/uso terapéutico , Francia , Alemania , Humanos , Irlanda , Factores de Riesgo , Reino UnidoRESUMEN
A Bavarian country doctor taking part in a course on evidence-based medicine, put the question whether there was any evidence that, in children with confirmed streptococcal infection of the respiratory tract, appropriate antibiotic treatment could reduce the risk of late complications. With the help of the German Institute for Medical Documentation and Information (DIMDI), we undertook a search of the literature, which, however, failed to turn up any information in support of a prophylactic effect of antibiotic treatment in such a case. To avoid jumping to hasty conclusions, however, the consequences that appear to suggest themselves, should be carefully considered. This example points up three major aspects of evidence-based medicine (attitude, tools and facts) that the doctor needs to acquire, and without which modern medicine will not be possible.
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Antibacterianos/uso terapéutico , Medicina Basada en la Evidencia , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Niño , Humanos , Faringitis/complicaciones , Factores de Riesgo , Infecciones Estreptocócicas/complicacionesRESUMEN
The impact of valvular, myocardial and pericardial abnormalities on cardiac haemodynamics in patients treated for Hodgkin's disease with COPP/ABVD with and without mediastinal irradiation was determined in 49 patients 2-10 years after induction therapy. Diagnostic procedures to evaluate cardiac function consisted of history, physical examination, exercise bicycle stress test, M-mode two-dimensional and pulsed Doppler echocardiography. No patient reported symptoms related to cardiomyopathy, and only one of the 49 had evidence of coronary heart disease. Pericardial thickening was seen on echocardiograms in 19/49 patients (38.8%), valvular thickening in 21/49 (42.9%), and reduced fractional shortening in 9/49 (18.4%). The Doppler-derived mean E and A (+/- SD) of transmitral flow were 0.75 +/- 0.14 m/s and 0.56 +/- 0.09 m/s, respectively, in patients receiving chemotherapy and 0.81 +/- 0.19 m/s and 0.63 +/- 0.20 m/s in those with additional mediastinal irradiation. There was no statistically significant difference between mean E and A in transmitral flow in patients treated for Hodgkin's disease and control subjects. Furthermore, the transtricuspid and hepatic vein flow velocities did not differ significantly. Although the present study demonstrates high frequencies of pericardial and valvular thickening in patients treated for Hodgkin's disease with the COPP/ABVD regimen with or without mediastinal irradiation, it showed no impact on cardiac flow velocities. The abnormalities might thus be of minor clinical relevance in these patients.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ecocardiografía Doppler , Cardiopatías/inducido químicamente , Enfermedad de Hodgkin/terapia , Adulto , Anciano , Terapia Combinada , Electrocardiografía , Femenino , Estudios de Seguimiento , Cardiopatías/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/radioterapia , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/fisiopatología , Radioterapia/efectos adversos , Válvula Tricúspide/fisiopatología , Función Ventricular/fisiologíaRESUMEN
49 patients (22 women, 27 men, mean age 43.7 [21-65] years) with Hodgkin's disease were examined by Doppler echocardiography a median of 5.37 (2-10) years after the end of chemotherapy (given according to the COPP/ABVD scheme, with or without mediastinal irradiation) for possible chronic changes in myocardium, pericardium or cardiac valves, as well as for any haemodynamic sequelae. Maximal and integrated early (E, Ei) and late (A, Ai) diastolic flow velocities and their ratio (E/A, Ei/Ai) were measured by pulsed Doppler over the mitral and tricuspid valves. Although on two-dimensional echo 21 patients (42.9%) were found to have valvar thickening, 19 (38.8%) pericardial thickening and 9 (18.4%) a reduced fibre shortening fraction, the Doppler indices were statistically not significantly different from those in 25 controls with normal hearts. These echocardiographic data of functional and morphological parameters indicate that there was no effect on various measurements of diastolic function after chemotherapy with or without mediastinal radiation. In successfully treated patients with Hodgkin's disease the described changes are of minor significance.
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Ecocardiografía Doppler , Corazón/efectos de los fármacos , Enfermedad de Hodgkin/complicaciones , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bleomicina/efectos adversos , Terapia Combinada , Ciclofosfamida/efectos adversos , Dacarbazina/efectos adversos , Doxorrubicina/efectos adversos , Ecocardiografía Doppler/instrumentación , Ecocardiografía Doppler/métodos , Ecocardiografía Doppler/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prednisona/efectos adversos , Procarbazina/efectos adversos , Dosificación Radioterapéutica , Inducción de Remisión , Factores de Tiempo , Vinblastina , Vincristina/efectos adversosRESUMEN
Only limited data is currently available on long-term gonadal toxicity and its impact on bone mineralization in men and women treated for Hodgkin's disease. The present study was therefore conducted to evaluate gonadal toxicity and bone loss in 49 patients with Hodgkin's disease 2-10 (median 5.37) years after chemotherapy. Most patients were treated with the COPP/ABVD regimen +/- irradiation according to the protocols of the German Hodgkin Study Group. Blood samples were tested for gonadotropins (FSH, LH), gonadal steroids, parathyroid hormone, osteocalcin, and calcitonin. Bone mineral density was measured using single- and dual-energy quantitative computed tomography as well as single-photon absorptiometry. FSH serum levels were significantly increased in 21/27 (80%) men demonstrating germ-cell aplasia. 13/15 (86%) men showed azoospermia after the COPP/ABVD regimen. In contrast, testosterone levels were within normal limits in all men tested, suggesting normal Leydig-cell function. 17/22 (77%) women exhibited increased FSH and LH levels, indicating premature ovarian failure. Women with therapy-induced ovarian failure had a significantly lower trabecular (98 +/- 34) and cortical (292 +/- 48 mg/cm3) spinal bone density than those with normal ovarian function. Men showed no evidence of bone loss after therapy. These data suggest severe gonadal toxicity in both men and women treated with the COPP/ABVD regimen. In female patients, drug-induced ovarian failure has a significant impact on bone mineralization.