Adverse drug reactions leading to urgent hospital admission in an elderly population: prevalence and main features.

PURPOSE: To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged ≥ 65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug-reaction associations. METHODS: A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged ≥ 65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. RESULTS: ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged ≥ 65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1-3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes (p = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. CONCLUSIONS: One out of every 30 urgent admissions of patients aged ≥ 65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs.

La «intervención del tercer día»: análisis de los factores asociados al seguimiento de recomendaciones sobre la prescripción de antibióticos / 'Third day intervention': An analysis of the factors associated with following the recommendations on the prescribing of antibiotics

IINTRODUCCIÓN: Los programas de control de uso de antibióticos suelen incluir intervenciones basadas en recomendaciones no impositivas a los prescriptores. Interesa conocer los factores relacionados con la adherencia a las recomendaciones y su funcionamiento en la práctica real. MÉTODOS: Estudio multicéntrico, controlado y aleatorizado, realizado en 32 unidades de hospitalización. Especialistas en enfermedades infecciosas revisaron, alrededor del tercer día, las prescripciones de antibióticos, estableciendo recomendaciones. Describimos la implantación de la intervención, analizamos los factores asociados al seguimiento de las recomendaciones y el impacto de la intervención. RESULTADOS: Se realizaron 3.192 intervenciones. Las fuentes de información empleadas para la elaboración de las recomendaciones variaron significativamente entre los centros. En el 65% se recomendó alguna modificación del tratamiento: suspender los antibióticos (47%), modificar la vía de administración (26%), cambiar o variar el número de antibióticos (27%) y cambiar la dosis (5%). En el 75% se recomendó simplificar el tratamiento. La adherencia fue del 68%, con variaciones significativas entre los centros, y fue mayor cuando se recomendó ajuste de dosis o cambio de vía, durante el primer periodo del estudio y cuando las recomendaciones se realizaban, además de por escrito, verbalmente. No se pudo constatar impacto en el consumo de antibióticos ni en la incidencia de patógenos resistentes. CONCLUSIONES: Una elevada proporción de tratamientos antibióticos son susceptibles de modificación, generalmente hacia la simplificación. La adherencia a las recomendaciones fue elevada, aunque variable, dependiendo del centro, del tipo de recomendación, del periodo del estudio y de que la recomendación se realizara mediante un comentario verbal además de escrito

INTRODUCTION: Stewardship programs on the use of antibiotics usually include interventions based on non-compulsory recommendations for the prescribers. Factors related to the adherence to expert recommendations, and the implementation of these programmes in daily practice, are of interest. METHODS: A randomized, controlled, multicentre intervention study was performed in 32 hospitalization units. Antibiotic prescriptions were evaluated by an infectious disease specialist on the third day. We describe the implementation of the intervention, the factors associated with adherence to recommendations, and the impact of the intervention. RESULTS: A total of 3,192 interventions were carried out. Information sources used to prepare the recommendations varied significantly between centres. A modification was recommended in 65% of cases: withdrawal (47%), change in administration route (26%), change of drugs or number of antibiotics (27%), and change in dose (5%). Simplification of treatment accounted for 75% of all recommendations. Adherence was 68%, with significant differences between hospitals, and higher when the recommendations consisted of a dose adjustment or change of route, during the first intervention period, and also when recommendations were personally commented on, in addition to writing a note in the clinical chart. We did not find any reduction in antibiotic consumption or variation in the incidence of resistant pathogens. CONCLUSIONS: An important proportion of antibiotic prescriptions may be susceptible to improvement, most of them towards simplification. The adherence to the intervention was high, but significant variations at different centres were observed, depending on the type of recommendation, and the study period. Those recommendations that were personally commented on were more followed more than those only written

['Third day intervention': an analysis of the factors associated with following the recommendations on the prescribing of antibiotics]. / La "intervención del tercer día": análisis de los factores asociados al seguimiento de recomendaciones sobre la prescripción de antibióticos.

INTRODUCTION: Stewardship programs on the use of antibiotics usually include interventions based on non-compulsory recommendations for the prescribers. Factors related to the adherence to expert recommendations, and the implementation of these programmes in daily practice, are of interest. METHODS: A randomized, controlled, multicentre intervention study was performed in 32 hospitalization units. Antibiotic prescriptions were evaluated by an infectious disease specialist on the third day. We describe the implementation of the intervention, the factors associated with adherence to recommendations, and the impact of the intervention. RESULTS: A total of 3,192 interventions were carried out. Information sources used to prepare the recommendations varied significantly between centres. A modification was recommended in 65% of cases: withdrawal (47%), change in administration route (26%), change of drugs or number of antibiotics (27%), and change in dose (5%). Simplification of treatment accounted for 75% of all recommendations. Adherence was 68%, with significant differences between hospitals, and higher when the recommendations consisted of a dose adjustment or change of route, during the first intervention period, and also when recommendations were personally commented on, in addition to writing a note in the clinical chart. We did not find any reduction in antibiotic consumption or variation in the incidence of resistant pathogens. CONCLUSIONS: An important proportion of antibiotic prescriptions may be susceptible to improvement, most of them towards simplification. The adherence to the intervention was high, but significant variations at different centres were observed, depending on the type of recommendation, and the study period. Those recommendations that were personally commented on were more followed more than those only written.

Anticoncepción hormonal y tromboembolia venosa / Hormonal contraception and venous thromboembolism

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Prevalence, risk factors and main features of adverse drug reactions leading to hospital admission.

PURPOSE: To assess the prevalence of hospital admission related to adverse drug reactions (ADRs) in a third-level hospital, to analyse the associated factors, and to describe the reactions and the drugs involved. METHODS: A cross-sectional study was conducted for a 120-day period. Patients that were urgently hospitalized entered the study. The primary endpoint was the ADR-related urgent admission. A descriptive analysis of demographic, clinical, and drug-related variables was performed. The association between the likelihood of urgent admission due to ADRs and age, gender, and number of drugs used was analysed. A descriptive analysis of the suspected drugs and the reactions in ADR-related admissions was performed. RESULTS: Overall, 186 out of 4,403 hospital admissions were due to ADRs (prevalence: 4.2 % [95 % CI 3.7-4.8 %]). Age (≥65 years: OR 1.59 [95 % CI 1.10-2.29]) and number of drugs used at the time of admission (3-5 drugs: OR 5.07 [95 % CI 2.71-9.59]; 6-9 drugs: OR 5.90 [95 % CI 3.16-11.0]; ≥10 drugs: OR 8.94 [95 % CI 4.73-16.89]), but not gender, were identified as independent factors associated with ADR-related hospitalization. The overall in-hospital stay for patients admitted with ADRs amounted to 1,785 days. The ADRs were mainly type A reactions (92 %). Acute renal failure related to renin-angiotensin system inhibitors, haemorrhage due to anticoagulants, and upper gastrointestinal bleeding related to antiplatelet drugs and/or non-steroidal anti-inflammatory drugs were the most frequent. CONCLUSION: Over 4 % of urgent hospitalizations are caused by ADRs, which are dose-related and predictable in more than 90 % of cases. The main risk factors are advanced age and polypharmacy.

An update on adenosine A2A receptors as drug target in Parkinson's disease.

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A(2A) receptors (A(2A)Rs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D(2) receptor (D(2)R). Furthermore, it is assumed that the formation of balanced A(2A)R/D(2)R receptor oligomers are essential for correct striatal function as the allosteric receptor-receptor interactions established within the oligomer are needed for properly sensing adenosine and dopamine. Interestingly, A(2A)R activation reduces the affinity of striatal D(2)R for dopamine and the blockade of A(2A)R with specific antagonists facilitates function of the D(2)R. Thus, it may be postulated that A(2A)R antagonists are pro-dopaminergic agents. Therefore, A(2A)R antagonists will potentially reduce the effects associated with dopamine depletion in Parkinson's disease (PD). Accordingly, this class of compounds have recently attracted considerable attention as potential therapeutic agents for PD pharmacotherapy as they have shown potential effectiveness in counteracting motor dysfunctions and also displayed neuroprotective and anti-inflammatory effects in animal models of PD. Overall, we provide here an update of the current state of the art of these A(2A)R-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Educational sessions in pharmacovigilance: What do the doctors think?

BACKGROUND: The aim of this study was to determine physicians' opinion regarding pharmacovigilance feedback sessions. A survey was conducted in a teaching hospital, and the physicians who attended the sessions were invited to participate by filling out a structured questionnaire. All sessions included a review of adverse drug reactions identified at the hospital and information on pharmacovigilance issues (news on warnings released by regulatory agencies or drug toxicity problems identified by recently published studies in medical journals). The survey questions were related to the interest, satisfaction, and belief in the utility of the sessions. A Likert scale (0-10 points) was used to assess physicians' opinions. FINDINGS: A total of 159 physicians attended the sessions and 115 (72.3%) participated in the survey. The mean (SD) age was 38.9 (12.1) years, and 72 (62.6%) were men. The mean (SD) scores of interest, satisfaction with the information provided, and belief in the utility of these sessions were 7.52 (1.61), 7.58 (1.46), and 8.05 (1.38) respectively. Significant differences were observed among physicians according to medical category and speciality in terms of interest, satisfaction, and belief in the utility of those sessions. CONCLUSIONS: Educational activities for physicians, such as feedback sessions, can be integrated into the pharmacovigilance activities. Doctors who attend the sessions are interested in and satisfied with the information provided and consider the sessions to be useful. Additional studies on the development and effectiveness of educational activities in pharmacovigilance are necessary.

Effect of an intervention on the features of adverse drug reactions spontaneously reported in a hospital.

OBJECTIVES: A continuous intervention based on healthcare management agreements was associated in our hospital with an increase in the absolute number of spontaneous reporting of adverse drug reactions (ADRs), and also with an increase in the number of reports of serious or unexpected ADRs and ADRs associated with new drugs. The objective was to analyse the effect of this intervention on the features of ADRs spontaneously reported in a hospital, the drugs involved and the number of signals identified. METHODS: A longitudinal study with two periods, the 1st period without intervention from 1998 to 2002 and the 2nd period with intervention from 2003 to 2005, was carried out in a tertiary teaching hospital. Changes between the two periods with regard to the following variables were analysed: the patients' characteristics, such as gender and age; the reported ADRs, and the medical assistance required; the suspected drugs involved in the ADRs; the main signals identified. RESULTS: Gender and age distribution of patients described in the spontaneous reports were no different in the two periods. During the second period, spontaneously reported cases requiring hospital admission and those occurring in hospital increased (236 from 2 in the first period and 277 from 99 in the first period respectively) and cases from outpatient hospital consultations began to be reported (13.9% of reports). The spontaneous reporting on all kinds of ADRs and drugs increased during the second period. Cutaneous reactions were the most frequently spontaneously reported ADRs in both periods followed by cardiovascular and neurological reactions in the first period, and haematological and gastrointestinal reactions in the second one. However, during the second period the higher increase was for endocrinological, urinary and hepatic reactions. Systemic antibiotics, anti-thrombotics and cardiac therapy drugs were the most common therapeutic subgroups reported to be suspected drugs in both periods, but in the second period the proportion of immunostimulants, beta blocking agents, immunosuppressants and psychoanaleptics increased. No signals were recognised during the first period; however, two signals and one additional safety concern were identified during the second. CONCLUSION: An intervention based on healthcare management agreements, was associated with an important increase in spontaneous reporting of ADRs by hospital physicians and also with a change in terms of the type of ADRs identified affecting different organs or systems, and the therapeutic groups of drugs involved. Future studies should analyse the effect of different types of intervention on the spontaneous reporting of ADRs in hospitals.

Consent in clinical trials: what do patients know?

OBJECTIVE: To assess participants' knowledge of key aspects about the clinical trials in which they are enrolled, describe the consent process, and assess the importance that investigators give to various aspects of trial information when verbally informing candidates. DESIGN: Prospective study based on a structured questionnaire interview of participants within 3 months after trial enrollment and an anonymous questionnaire sent to clinical trial investigators. SUBJECTS: A total of 140 participants included in 40 clinical trials were interviewed, and 51 investigators answered the questionnaire. RESULTS: The formal steps to obtain informed consent were usually carried out. Participants were aware of the purpose of the trial and the right to discontinue participation, but only 23% knew that treatment was randomly allocated, 57% knew they might receive a placebo, and 42% was aware that adverse effects could occur. Patients who had read the information sheet had better knowledge of most aspects, except for the risk of adverse effects. The investigators considered that compensation, insurance coverage, possibility of receiving a placebo, and treatment allocation were the least important aspects of the trial when informing candidates for participation. CONCLUSIONS: Although the formal steps for obtaining informed consent were usually carried out, a relevant percentage of patients included in clinical trials were unaware of important aspects of their participation. Patients showed more limited knowledge about the same points that investigators considered less important when informing potential participants. Deferring signature on the consent form and encouraging reading of the information sheet may improve participants' knowledge about clinical trials.

Antimicrobianos y embarazo / Antimicrobials and pregnancy

Los cambios fisiológicos que ocurren durante el embarazo condicionan cambios farmacocinéticos que pueden alterar la efectividad de los antimicrobianos y, además, hay que tener en cuenta el posible riesgo teratogénico y la toxicidad de estos medicamentos sobre el embrión y el feto. En general, las mujeres embarazadas son excluidas de los ensayos clínicos y hay escasa información farmacocinética respecto al uso y la dosificación adecuados de los antimicrobianos en las mujeres embarazadas. Además, la mayoría de antimicrobianos cruzan la barrera hematoplacentaria, pero los datos relacionados con su potencial teratogénico y su toxicidad fetal y neonatal también son limitados y tienen una fiabilibad variable. En este artículo se revisan las evidencias disponibles y de mayor relevancia clínica relacionadas con la farmacología de diferentes antibacterianos, antifúngicos, antivirales y antiparasitarios en las mujeres embarazadas, con un énfasis especial en los datos de toxicidad fetal (AU)

The physiologic changes that occur during pregnancy result in pharmacokinetic changes that can alter the effectiveness of antimicrobial agents. The possible risk of teratogenic and toxic effects of antimicrobials on the fetus is an additional cause of concern. In general, pregnant women are excluded from clinical trials and there is little pharmacokinetic information on the use and proper dosing of antimicrobials in this population. Although most antimicrobials can cross the placental blood barrier, data on the potential teratogenic effects, and fetal and neonatal toxicity caused by antimicrobials are also limited and of varying reliability. This article reviews the available evidence with the greatest clinical relevance regarding the pharmacology of different antibiotic, antifungal, antiviral, and antiparasitic agents in pregnancy, with particular focus on data related to fetal toxicity (AU)

[Antimicrobials and pregnancy]. / Antimicrobianos y embarazo.

The physiologic changes that occur during pregnancy result in pharmacokinetic changes that can alter the effectiveness of antimicrobial agents. The possible risk of teratogenic and toxic effects of antimicrobials on the fetus is an additional cause of concern. In general, pregnant women are excluded from clinical trials and there is little pharmacokinetic information on the use and proper dosing of antimicrobials in this population. Although most antimicrobials can cross the placental blood barrier, data on the potential teratogenic effects, and fetal and neonatal toxicity caused by antimicrobials are also limited and of varying reliability. This article reviews the available evidence with the greatest clinical relevance regarding the pharmacology of different antibiotic, antifungal, antiviral, and antiparasitic agents in pregnancy, with particular focus on data related to fetal toxicity.

The DEC-net European register of paediatric drug therapy trials: contents and context.

OBJECTIVE: To describe the results and conclusions of DEC-net, an international, publicly available register of paediatric drug therapy clinical trials, and to assess which paediatric health areas are covered by research and by which trial types. METHODS: The contents of the register, which was set up by four groups (Italy, UK, France, Spain) who searched for paediatric trials and collected data between 2004-2006, were analysed. The disease areas reflected were compared with those covered by published trials and Burden of Disease (BD) data. RESULTS: In all, 257 trial records were analysed, 86 of which were entered by the Italian partner, 84 by the UK partner, 56 by the French partner and 31 by the Spanish partner. Spain entered the majority of multinational trials, while the UK had the majority of single-centre national trials. Most trials were experimental (79%), and the most commonly represented diseases were neoplasms (14% trials). In all, 28% were double-blind randomised controlled trials (RCTs). The most common disease areas addressed in the 257 trials were similar to the published trials' areas. In contrast, the primary research area was low on the BD list. CONCLUSIONS: DEC-net has demonstrated that international research efforts exist, even for paediatrics, although there may be an imbalance between national and multinational studies and a limited approach to double-blind RCTs. Recent initiatives will increase the number of children participating in research, and European legislation will require prospective registration. Paediatric research priorities must be better defined, however, and this can be done by registering research and making the information available to all relevant actors.

Use of venous thromboprophylaxis and adherence to guideline recommendations: a cross-sectional study.

BACKGROUND: Consensus Conferences and Guidelines for deep vein thrombosis prophylaxis have been published, which recommend the use of prophylactic heparins in patients with risk of venous thromboembolism (VTE). The aim of this study was the assessment of the prophylaxis of VTE and the adherence to accepted guideline recommendations throughout the hospital. METHODS: A cross-sectional study was carried out in a teaching hospital after guidelines were implemented. Patients' risk factors of deep vein thrombosis, risk categories of patients, and prophylaxis used in different wards were recorded. Appropriate adherence to the guidelines was analysed. RESULTS: Of 397 patients, prophylaxis was used in 231 patients (58%), and low-molecular-weight heparins (LMWH) were used in 224 of them (97%). Patients with prophylaxis had a higher mean number of risk factors (SD) than those without prophylaxis [3.1 (1.4) vs 1.9 (1.4); p < 0.05)]. Prophylaxis was used in 72% and 90% of moderate and high-risk patients respectively. Appropriate adherence to all guideline recommendations was observed in 42% of patients. Adherence to guidelines was high as regards the use of prophylaxis according to patients' risk factors (78%) and the use of appropriate types of prophylaxis (99%), but was low regarding appropriate heparin dosage (47%) and preoperative dosage (37%). Appropriate prophylaxis use was higher in critical care and surgical wards than in medical wards. CONCLUSION: Prophylaxis of VTE is generally used in risk patients, but appropriate adherence to guidelines is less frequent and variable among different wards. Continuing medical education, discussion and dissemination of guidelines, and regular clinical audit are necessary to improve prophylaxis of VTE in clinical practice.

[Generic drug prescription at discharge from a hospital emergency service]. / Prescripción de medicamentos genéricos en pacientes dados de alta de un servicio hospitalario de urgencias.

BACKGROUND AND OBJECTIVE: Drug prescription at hospital discharge often implies continuation of the treatment in primary health care. The aim of this study was to assess prescription of generics at discharge from a hospital emergency service. MATERIAL AND METHOD: Longitudinal and retrospective study, on a random sample of medical reports in a hospital emergency service during one year (August 2000 to July 2001). Information on the medical specialty, prescribed generic drugs and marked availability of the corresponding generic drugs pharmaceutical specialties was collected. Factors associated with generic prescription were analyzed by means of logistic regression analysis. RESULTS: A sample of 1,245 medical reports was selected in which 2,315 drugs were prescribed. Although generic drugs were available for 33.3% (CI 95%, 31.4-35.2) of prescriptions, 9.5% (95% CI, 8.3-10.7) of prescribed drugs were generics. The average price of trademark prescribed medicines, for which there was a generic equivalent, was 7.09 Euros (95% CI, 6.54-7.63 Euros), and that of the corresponding generic versions was 5.08 Euros (95% CI, 4.68-5.48 Euros). Variables associated with generic drug prescription included the particular study period (OR=1.35; 95% CI, 0.99-1.84), the medical specialty of the prescriber (OR=1.40; 95% CI, 1.05-1.86), availability of generic drugs (OR=1.76; 95% CI, 1.30-2.39) and low price of prescribed drugs (OR=2.67; 95% CI, 1.80-3.98). CONCLUSION: In spite of the availability of generic drugs, prescription of generic drugs at discharge of this hospital emergency service was low. Prescription and use of generic drugs should be promoted in hospitals.

Prescripción de medicamentos genéricos en pacientes dados de alta de un servicio hospitalario de urgencias / Generic drug prescription at discharge from a hospital emergency service

FUNDAMENTO Y OBJETIVO: La prescripción de medicamentos al alta hospitalaria implica a menudo la continuación del tratamiento en atención primaria. El objetivo del presente estudio fue evaluar la prescripción de medicamentos genéricos al alta en un servicio hospitalario de urgencias. MATERIAL Y MÉTODO: Estudio descriptivo, longitudinal y retrospectivo, sobre una muestra aleatoria de informes médicos de un servicio hospitalario de urgencias durante un año (agosto de 2000 a julio de 2001). Se recogió información sobre la especialidad del médico, los medicamentos genéricos prescritos y la oferta correspondiente de especialidades farmacéuticas genéricas (EFG). Los factores asociados con la prescripción de medicamentos genéricos se analizaron mediante análisis de regresión logística. RESULTADOS: Se seleccionó una muestra de 1.245 informes médicos en los que constaban 2.315 medicamentos prescritos. A pesar de que existía oferta de EFG para un 33,3 por ciento (intervalo de confianza [IC] del 95 por ciento, 31,4-35,2) de las prescripciones, éstas especificaban una EFG en un 9,5 por ciento (IC del 95 por ciento, 8,3-10,7) de los casos. El precio medio de los medicamentos de marca comercial prescritos para los que había oferta de EFG fue de 7,09 e (IC del 95 por ciento, 6,54-7,63 e ) y el de las EFG correspondientes, de 5,08 e (IC del 95 por ciento, 4,68-5,48 e ). Las variables asociadas con la prescripción de medicamentos genéricos fueron el período (odds ratio [OR] = 1,35; IC del 95 por ciento, 0,99-1,84), la especialidad del médico (OR = 1,40; IC del 95 por ciento, 1,051,86), la oferta de EFG (OR = 1,76; IC del 95 por ciento, 1,30-2,39) y el precio bajo del medicamento prescrito (OR = 2,67; IC del 95 por ciento, 1,80-3,98). CONCLUSIÓN: La prescripción de los medicamentos genéricos en los informes de alta de este servicio de urgencias hospitalarias fue reducida, a pesar de que en muchos casos había EFG disponibles. Es necesario fomentar la prescripción y el uso de medicamentos genéricos en los hospitales (AU)