ABSTRACT
BACKGROUND: Benzodiazepines are extensively used in primary care, but their long-term use is associated with adverse health outcomes and dependence. AIMS: To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use. METHOD: A multicentre three-arm cluster randomised controlled trial was conducted, with randomisation at general practitioner level (trial registration ISRCTN13024375). A total of 532 patients taking benzodiazepines for at least 6 months participated. After all patients were included, general practitioners were randomly allocated (1:1:1) to usual care, a structured intervention with follow-up visits (SIF) or a structured intervention with written instructions (SIW). The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription claims at 12 months. RESULTS: At 12 months, 76 of 168 (45%) patients in the SIW group and 86 of 191 (45%) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 (15%) in the control group. After adjusting by cluster, the relative risks for benzodiazepine discontinuation were 3.01 (95% CI 2.03-4.46, P<0.0001) in the SIW and 3.00 (95% CI 2.04-4.40, P<0.0001) in the SIF group. The most frequently reported withdrawal symptoms were insomnia, anxiety and irritability. CONCLUSIONS: Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity. A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits.
Subject(s)
Benzodiazepines/adverse effects , Patient Education as Topic/methods , Primary Health Care/methods , Substance Withdrawal Syndrome/prevention & control , Substance-Related Disorders/therapy , Aged , Cluster Analysis , Female , Humans , Interviews as Topic , Male , Middle Aged , Spain , Treatment OutcomeABSTRACT
El presente artículo describe la regulación del peculiar concurso de traslados de oficinas de farmacia en la Comunidad Autónoma de Canarias. Se comenta asimismo el concurso de aperturas, por su conexión con el anterior. Se investigan las razones justificativas de la normativa canaria y, se comparan las alternativas similares de otras comunidades, como el baremo para el concurso de aperturas de la Comunidad Valenciana. Finalmente se enumeran los principales inconvenientes de este sistema
The present paper describes in detail the peculiar move procedure of the chemist shops that takes place in the Canary Island. It can be performed in any place of the Community. The paper also comments the procedure for new establishment installation, as it is clearly related. The reasons justifying the regulation are investigated and some other possibilities used by different autonomic governments are compared, as the merit scale used by the Valenciana Community. The disadvantages of the move procedure are also pointed out
Subject(s)
Humans , Pharmacy Service, Hospital/organization & administration , Pharmacy Service, Hospital/standards , Legislation as TopicABSTRACT
OBJECTIVE: To assess the quality and relevance of adverse drug reactions (ADRs) published as Letters to the Editor (LE) in Spanish medical journals. DESIGN: Observational study. PARTICIPANTS: LE on adverse drug reactions published over 5 years (1994-98). SETTING: Four Spanish medical journals (Medicina Clínica, Revista Clínica Española, Atención Primaria and Anales de Medicina Interna). MAIN MEASUREMENTS: Patient characteristics, drugs, ADR, causality algorithm, minimum criteria, and publication relevance. RESULTS: Out of 2244 LE, 204 (9.1%) reported ADRs, which included 235 cases. The therapeutic subgroups most commonly implicated were anticoagulants and antiplatelet drugs, antibiotics, and antineoplastic agents; 20.4% of the drugs were recently marketed. ADRs most commonly involved the nervous system (13.6%), liver (10.2%), skin and appendages (9.8%), general reactions (9.8%), and the digestive system (8.1%). The reactions were moderate in 50.2% of cases and severe/fatal in 34%. The mean causality algorithm value (5.9+/-2.2) was similar among journals. Of the ADRs, 28 (11.9%) were definitive, 182 (77%) possible or probable, and 26 (11.1%) improbable or conditional; 10.2% were unknown. There were no differences in the mean minimum publication criteria (9.5+/-1.2). Publication relevance was 3.2+/-1.6 points, and higher in Medicina Clínica. CONCLUSIONS: ADRs constitute an important part of LE in the journals studied. The causal relationship is acceptable, the documentation quality is high, with few unknown reactions and ADRs to recently marketed drugs. Relevance is generally low, although greater in Medicina Clínica.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Family Practice , Internal Medicine , Periodicals as Topic/standards , Publishing/standards , Correspondence as Topic , SpainABSTRACT
Objetivo. Conocer la calidad y la relevancia de las reacciones adversas a medicamentos (RAM) publicadas como Cartas al Director en las revistas médicas españolas. Diseño. Estudio descriptivo. Participantes. Cartas al director sobre RAM aparecidas durante 5 años (1994-98). Emplazamiento. Cuatro revistas españolas (Medicina Clínica, Revista Clínica Española, Atención Primaria y Anales de Medicina Interna). Mediciones principales. Las características de los pacientes, de los medicamentos, de las reacciones adversas, el algoritmo de causalidad, los criterios mínimos y la relevancia de la publicación. Resultados. De 2.244 cartas, 204 (9,1%) se referían a RAM e incluían 235 casos. Los subgrupos terapéuticos más implicados fueron: anticoagulantes y antiplaquetarios, antibióticos y antineoplásicos. El 20,4% de los medicamentos era reciente. Las RAM más frecuentes afectaron al sistema nervioso (13,6%), el hígado (10,2%), la piel y anejos (9,8%), reacciones generales (9,8%) y aparato digestivo (8,1%). El 50,2% fueron moderadas y el 34%, graves/mortales. El valor medio (5,9 ± 2,2) del algoritmo de causalidad fue similar entre revistas; las RAM fueron: 28 (11,9%) definidas, 182 (77%) posibles o probables y 26 (11,1%) improbables o condicionales; el 10,2% eran desconocidas. No se detectaron diferencias en la media (9,5 ± 1,2) de criterios mínimos de publicación. La relevancia de la publicación fue de 3,2 ± 1,6 puntos, superior en Medicina Clínica. Conclusiones. La publicación de RAM supone una parte importante de la sección de Cartas al Director en las revistas estudiadas. La relación de causalidad es aceptable y la calidad documental elevada, con pocas reacciones desconocidas y a medicamentos recientes. La relevancia ha sido escasa, aunque superior en Medicina Clínica
Objective. To assess the quality and relevance of adverse drug reactions (ADRs) published as Letters to the Editor (LE) in Spanish medical journals. Design. Observational study. Participants. LE on adverse drug reactions published over 5 years (1994-98). Setting. Four Spanish medical journals (Medicina Clínica, Revista Clínica Española, Atención Primaria, and Anales de Medicina Interna). Main measurements. Patient characteristics, drugs, ADR, causality algorithm, minimum criteria, and publication relevance. Results. Out of 2,244 LE, 204 (9.1%) reported ADRs, which included 235 cases. The therapeutic subgroups most commonly implicated were anticoagulants and antiplatelet drugs, antibiotics, and antineoplastic agents; 20.4% of the drugs were recently marketed. ADRs most commonly involved the nervous system (13.6%), liver (10.2%), skin and appendages (9.8%), general reactions (9.8%), and the digestive system (8.1%). The reactions were moderate in 50.2% of cases and severe/fatal in 34%. The mean causality algorithm value (5.9±2.2) was similar among journals. Of the ADRs, 28 (11.9%) were definitive, 182 (77%) possible or probable, and 26 (11.1%) improbable or conditional; 10.2% were unknown. There were no differences in the mean minimum publication criteria (9.5±1.2). Publication relevance was 3.2±1.6 points, and higher in Medicina Clínica. Conclusions. ADRs constitute an important part of LE in the journals studied. The causal relationship is acceptable, the documentation quality is high, with few unknown reactions and ADRs to recently marketed drugs. Relevance is generally low, although greater in Medicina Clínica
Subject(s)
Humans , Adverse Drug Reaction Reporting Systems/organization & administration , Periodicals as Topic/statistics & numerical data , Pharmacoepidemiology/trends , 51706ABSTRACT
Se revisa la normativa relativa a la propiedadde las farmacias respecto a la disposición deque únicamente puede ostentar la propiedadde una farmacia (Reales Ordenanzas -derogadas-,leyes autonómicas de ordenación farmacéutica).Se alude asimismo a la normativa que contemplalos procedimientos de autorización (Ordende 21 de noviembre de 1979 y Orden de17 de enero de 1980 del Ministerio de Sanidady Seguridad Social) que representaron una garantíadel cumplimiento de este requisito. Secomentan algunas sentencias que ponen demanifiesto la problemática que ha surgido endeterminados momentos
The ruIes applying to the owners of the Spanishpharmacy establishments that restrict thepossibility to one establishment are reviewed.The procedures to obtain an authorization(Order of 21st November 1979 and Order of17th January 1980 from the Social Insuranceand Health Ministry) are also cited as theyconstituted a guarantee of requirement accomplishment.Some sentences considering illegalsituations are commented in order to point outthe importance of the rules
Subject(s)
Licensure, Pharmacy/legislation & jurisprudence , Licensure, Pharmacy/standards , Legislation, Pharmacy/standards , Pharmacies/legislation & jurisprudence , Pharmacies/standardsABSTRACT
INTRODUCTION: Scarce information about comparative diagnostic and therapeutic patterns in paediatric outpatients of different countries is found in the literature. OBJECTIVE: To describe the similarities and differences observed in diagnosis and therapeutic patterns of paediatric patients of seven locations in different countries. DESIGN: Cross-sectional, prospective, international comparative, descriptive study. PATIENTS AND METHODS: A randomly selected sample of 12,264 paediatric outpatients seen in consultation rooms of urban and rural areas and attended by paediatricians or general practitioners of the participating locations. Data on patient demographic information, diagnosis and pharmacological treatment were collected using pre-designed forms. Diagnoses were coded using the ICD-9 and drugs according to the ATC classification. RESULTS: Among the ten most common diagnoses, upper respiratory tract infections are in the first position in all locations; asthma prevalence is highest in Tenerife (8.4%). Tonsillitis, otitis, bronchitis and dermatological affections are the most common diagnoses in all locations. Pneumonia is only reported in Sofia (3.8%) and Smolensk (2.3%). The average number of drugs prescribed per child varied from 1.3 in Barcelona to 2.9 in Smolensk. There are no great differences in the profile of pharmacological groups prescribed, but a considerable range of variations in antibiotic therapy is observed: prescription of cephalosporins is low in Smolensk (0.7%) and higher in the other locations, from 16.5% (Bratislava) to 28% (Tenerife). Macrolides prescriptions range from 12.6% (Toulouse) to 24.7% (Smolensk), except in Sofia where they drop to 5.6%. Trimethoprim and its combinations are used in Smolensk (23.3%), Sofia (11.8%) and Bratislava (8.7%). Check-up consultations are not recorded in Smolensk and Bratislava, whereas in Toulouse these visits account for 16.2% of all consultations and in the other locations the percentage varies from 6.1% (Tenerife) to 1.9% (Sofia). Homeopathic treatments are registered only in Toulouse. CONCLUSION: Except in asthma prevalence, there are no great differences in diagnostic maps among locations. Significant variations in the number of drugs prescribed per child and antibiotic therapies are observed. Areas for improvement have been identified.
Subject(s)
Pharmaceutical Preparations/administration & dosage , Practice Patterns, Physicians' , Bulgaria , Child , Cross-Sectional Studies , Data Collection , Drug Prescriptions , Drug Utilization , France , Humans , Outpatients , Prospective Studies , Russia , Slovakia , SpainABSTRACT
OBJECTIVE: To describe patterns observed in the treatment of acute otitis media (AOM) in several locations of five countries. PATIENTS AND METHODS: Cross-sectional, descriptive study. Random sample of 12,264 paediatric outpatients seen by paediatricians or general practitioners (GPs). Data on patient demographics, diagnoses and treatment were collected. Diagnoses were coded by ICD-9 and drugs by ATC classification. Patients diagnosed with AOM (ICD-9 codes: 381 and 382) were selected for analysis. RESULTS: Cases of AOM (873) accounted for 7.1% of the sample. There is a clear variation in the percentage of children diagnosed with AOM and treated with antibiotics in the different locations, antibiotic prescriptions being higher in Barcelona (93% of children), and lowest in Smolensk (56.4 % of children were treated without antibiotics). The antibiotics used varied widely: ampicillin use is almost limited to Smolensk (26.7%) and Bratislava (13.8%), whereas amoxicillin plus clavulanic acid is the choice in Toulouse (33.8%), Valencia (30.2%) and Barcelona (28.9%), and cephalosporins are more frequently prescribed in Tenerife (51.7%). Finally, macrolides are used in Barcelona (18.3%), Valencia (17.5%) and Tenerife (13.6%), but not prescribed in Toulouse or Sofia. Prescriptions of anti-inflammatory drugs were only relevant in Valencia (31.7%), Tenerife (27.2%) and Toulouse (17.4%) and of otological preparations in Sofia, where almost each child received ear drops (91.9%). Nasal preparations are commonly used only in Sofia (41.9%), Bratislava (65.5%) and Smolensk (68.6%). CONCLUSION: Despite the general agreement of most guidelines, wide differences in the treatment of uncomplicated AOM in children are observed. Non-antibiotic therapy for AOM and the use of first-choice antibiotics should be more actively encouraged in the primary care centres. Studies to measure prevailing rates of antibiotic resistance in these populations are needed.
Subject(s)
Otitis Media/drug therapy , Otitis Media/epidemiology , Acute Disease , Administration, Topical , Amoxicillin-Potassium Clavulanate Combination/administration & dosage , Amoxicillin-Potassium Clavulanate Combination/therapeutic use , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/classification , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Cephalosporins/administration & dosage , Cephalosporins/therapeutic use , Child , Cross-Sectional Studies , Drug Prescriptions/statistics & numerical data , Drug Utilization Review , Europe/epidemiology , Europe, Eastern/epidemiology , Humans , International Classification of Diseases , Macrolides/administration & dosage , Macrolides/therapeutic use , Otitis Media/diagnosis , Practice Patterns, Physicians'ABSTRACT
OBJECTIVE: To analyze the case reports concerning children (14 years or younger) in the Spanish Pharmacovigilance System over a 10-year period (1982-1991). FINDINGS: The study of 1419 reports of adverse drug reaction (9.8% of all those received) showed the most commonly involved organs and systems to be the skin, digestive tract, and nervous system (62.8%). The most commonly involved pharmacological groups were antibiotics, respiratory medications, and vaccines (69%). The absolute number of reports is higher in children between 1 and 4 years of age (37.9%). There were more reports among males than in females. Less than 5% of the reports notified directly life-threatening or fatal reactions. CONCLUSIONS: Adverse drug reaction are not common in pediatric patients, and most are mild. However, due to limitations of clinical trials in children, pharmacoepidemiological studies may be the only source of information on the benefit-risk profile of drugs received by these patients, and as such require special attention.
Subject(s)
Adverse Drug Reaction Reporting Systems , Drug-Related Side Effects and Adverse Reactions , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Pharmacoepidemiology , Spain/epidemiologySubject(s)
Gynecomastia/etiology , Panax/adverse effects , Plants, Medicinal , Adult , Breast Diseases/etiology , Humans , Male , Pain/chemically inducedABSTRACT
AIMS: There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. METHODS: An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. RESULTS: A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR=1.66, 95% CI 1.03-2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. CONCLUSIONS: Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Child, Hospitalized , Child, Preschool , Female , Humans , Infant , Male , Probability , Prospective Studies , Sex FactorsSubject(s)
Antidepressive Agents/adverse effects , Dopamine Antagonists/adverse effects , Dystonia/chemically induced , Fluvoxamine/adverse effects , Metoclopramide/adverse effects , Selective Serotonin Reuptake Inhibitors/adverse effects , Acute Disease , Adolescent , Drug Interactions , Drug Therapy, Combination , Humans , MaleABSTRACT
1. A study is made of the contractile and relaxant effects, and mechanism of action, of histamine on isolated uterus from mice treated with diethylstilboestrol, employing acetylcholine and adrenaline as contractile and relaxant standard agents. 2. Concentration-response curves for histamine agonists were obtained in the absence and presence of selective histaminergic blocking drugs (clemizole, ranitidine and thioperamide) and indomethacin. A number of experiments were carried out in uterus from reserpinised mice. Concentration-response curves for acetylcholine and adrenaline were also obtained in the absence and presence of their selective antagonist (atropine and propranolol). 3. In isolated oestrogenised mouse uterus, histamine and acetylcholine produced a concentration-related contractile response. When the uterus was precontracted with KCl, histamine at lower doses produced a slight contraction, though in the presence of clemizole it induced concentration-related relaxation, reminiscent of that produced by adrenaline. Atropine and propranolol antagonised the contractile and relaxant effects of acetylcholine and adrenaline, respectively. 4. In isolated uterus from reserpinised mice, histamine and 2-pyridylethylamine, but not 4-methylhistamine, produced a concentration-related contractile response. Ranitidine potentiated the contractile effect of histamine, though clemizole--in the presence of ranitidine--competitively antagonised the contractile effect of histamine (pA2 = 10.50 +/- 0.81). The concentration-relaxant curve of histamine in the presence of clemizole was not modified by ranitidine or indomethacin, but shifted to the right with thioperamide. The same displacement was also observed in the presence of clemizole plus ranitidine. 5. In mouse isolated uterus, histamine mainly produced contraction mediated by histamine H1-receptors, though the existence of histamine H2- or H3-receptors mediating relaxation could not be excluded.
Subject(s)
Histamine Agonists/pharmacology , Histamine Antagonists/pharmacology , Histamine/pharmacology , Uterine Contraction/drug effects , Acetylcholine/pharmacology , Animals , Atropine/pharmacology , Diethylstilbestrol/pharmacology , Dose-Response Relationship, Drug , Drug Interactions , Female , Mice , Parasympatholytics/pharmacology , Uterus/drug effects , Vasodilator Agents/pharmacologyABSTRACT
1. We carried out experiments in anesthetized rats to study the hemodynamic effects of intravenous injections of epinine. 2. Epinine (1-320 micrograms/kg) produced a biphasic effect on mean arterial blood pressure (n = 30). At doses lower than 40 micrograms/kg, arterial blood pressure decreased (by as much as 21.5 +/- 3.4%), though at higher doses it increased dose dependently (by as much as 73.2 +/- 14.5%). Epinine also produced bradicardia in a dose-dependent manner (by as much as 26.4 +/- 4.9%). Sulpiride (100 micrograms/kg) suppressed the hypotensive effect of epinine but did not change the hypertensive effect. In the presence of prazosin (1,000 micrograms/kg), arterial blood pressure remained significantly decreased at all doses of epinine. Neither sulpiride nor prazosin changed the bradycardic effect of epinine. 3. Prazosin produced a significant decrease in renal vascular resistance. Epinine (5 micrograms/kg) after prazosin reverted the effects of prazosin in renal vascular resistance, without any significant modification in the renal blood flows. However, 20 micrograms/kg epinine increased the renal vascular resistances and, moreover, produced a significant decrease in the blood flows of both kidneys. Neither prazosin nor epinine produced modifications in the intestinal vascular bed. 4. Although epinine possesses significant dopamine and alpha-adrenergic activities that are involved in the biphasic effect of the agent on mean arterial blood pressure in anesthetized rats, in the presence of prazosin, it is not possible to manifest dopaminergic activity involved in the increase in renal or mesenteric blood flow; this may be due to the low tone of the vascular wall induced by the alpha-adrenergic antagonist, though an alpha 2-activity cannot be discarded.
Subject(s)
Blood Pressure/drug effects , Deoxyepinephrine/pharmacology , Dopamine Agonists/pharmacology , Vascular Resistance/drug effects , Anesthetics, Intravenous , Animals , Heart Rate/drug effects , Rats , Rats, Wistar , Renal Circulation/drug effects , Splanchnic Circulation/drug effects , UrethaneSubject(s)
Amoxicillin/adverse effects , Esophagitis/chemically induced , Penicillins/adverse effects , Aged , Humans , Male , TabletsABSTRACT
OBJECTIVE: To describe two cases of stomatitis related to fluoxetine given for the treatment of depression that were detected in the hospital emergency department. DATA SYNTHESIS: Two women developed stomatitis after the intake of fluoxetine for the treatment of depression. One of the patients had six recurrent episodes of stomatitis without suspecting an association with fluoxetine. No other drugs were administered during these episodes. The second patient was treated concurrently with fluoxetine and bentazepam. In both patients the lesion improved upon discontinuation of fluoxetine, even though the second patient continued to take a different benzodiazepine. DISCUSSION: Stomatitis related to fluoxetine has not been previously reported in clinical trials or in the literature. According to the causal algorithm used by the Spanish Drug Surveillance Schemes, the first case constituted a defined adverse reaction and the second was probable. CONCLUSIONS: Our observations suggest that fluoxetine may be considered as a probable cause of stomatitis. The reporting of isolated cases of adverse drug reactions (ADRs) makes it possible to define the toxicity profile of recently marketed drugs such as selective serotonin-reuptake inhibitors, including fluoxetine. Emphasis is placed on the potential role played by emergency departments in detecting ADRs.
Subject(s)
Antidepressive Agents, Second-Generation/adverse effects , Fluoxetine/adverse effects , Stomatitis/chemically induced , Adult , Anorexia Nervosa/drug therapy , Depression/drug therapy , Female , HumansABSTRACT
1. A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). the proportion of suspected ADRs related to hospital admissions was 4.3%. 2. The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3. The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4. There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37-2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72-5.42). 5. The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group.
