Aspirin or acetaminophen? A comparison from data collected by the Spanish Drug Monitoring System.

To characterize and compare the toxicity profiles of aspirin and acetaminophen when used by large populations, all records of adverse drug reactions to these drugs reported to the Spanish Drug Monitoring System from 1982 to 1991 were analyzed. According to these data, aspirin-induced reactions were more serious than those reactions to acetaminophen; the severity of all the reactions in both cases was associated with time of exposure and with the accumulated dose administered. For GI reactions to aspirin no association was found between severity and time of exposure or dose, although an association with age was found. There were no differences between the proportions of deaths, malformations, and renal damage recorded for either of the two groups. Proportions of hematological and hepatic disturbances were greater with acetaminophen. Adverse drug reaction data for aspirin and acetaminophen from spontaneous reporting seem to be consistent with data coming from observational studies.

Pharmacoepidemiology in practice. Current status and future trends.

Pharmacoepidemiology is the application of epidemiological reasoning, methods and knowledge to the study of the uses and effects (beneficial and adverse) of drugs in human populations. As referred to by the term 'pharmacoepidemiology', the discipline now enters into its second decade, although its origins go back to the beginnings of this century. This article reviews the opinions of leading pharmacoepidemiologists on the scope and prospects for pharmacoepidemiology, and summarises the most important challenges that the discipline faces on its way towards the next century. The future of pharmacoepidemiology requires the development of research methods more able to cope with the specific problems posed by the study of drugs, notably the issue of confounding by indication and the ability to adjust accurately for severity of disease. Capacity building should also continue during the next years; training of professionals, the optimisation of computerised databases for research purposes and their joint use with more traditional epidemiological methods are major challenges. From a public health perspective, a critical task is to assess the impact that vaccines and drugs have on the overall patterns of disease in well defined populations.

[DTP vaccine and infant sudden death syndrome. Meta-analysis]. / Vacuna DTP y síndrome de muerte súbita del lactante. Un metaanálisis.

BACKGROUND: At the beginning of 1994, five cases of sudden infant death syndrome after DTP immunization appeared in Spain. In order to study a causal relationship a meta-analysis of the different studies that assess this possibility has been conducted. METHODS: The selection criteria was epidemiological study, case-control or cohort, assessing risk of sudden infant death syndrome in immunized versus non-immunized infants or risk of sudden infant death syndrome in recently immunized infants versus immunized infants beyond 30 days. Pooled risk ratios were calculated from adjusted risk ratios, when available, of the different studies, by a meta-analysis according the method described by Greenland. RESULTS: One cohort and four case-control studies were selected. Pooled risk ratio for immunized versus non-immunized infants was 0.67 (95% CI = 0.60-0.75). When comparing risk of sudden death syndrome in up to 30 days immunized infants versus more than 30 days immunized infants, the pooled risk ratio was 1.00 (95% CI = 0.84-1.20). CONCLUSIONS: DTP-immunization does not seem to increase the risk of sudden infant death syndrome. The risk of sudden infant death syndrome is not greater in the first thirty days following immunization. These data indicate a lack of association between DTP immunization and sudden infant death syndrome.

[Changes in the pattern of opioid analgesic consumption in Spain]. / Cambios en el patrón de consumo de analgésicos opioides en España.

BACKGROUND: Data from different sources have proved an infrautilization of opioid analgesics in Spain. A descriptive study has been conducted in order to know the utilization of these drugs and changes in the pattern of use in the last few years. MATERIAL AND METHOD: To know the consume of narcotic analgesic drugs, N02A group of the Anatomic Therapeutic Classification, a search was developed in the ECOM database from the Spanish Ministry of Health. This database contains information of drug preparations prescribed throughout the National Health Care System. RESULTS: The consumption of opioid analgesics in Spain has been multiplied by 5.2 during this period. It has increased from 94.7 defined daily dose per 1,000,000 inhabitants in 1985 to 489.4 in 1994. The most consumed drug in 1994 was dihydrocodeine, followed by tramadol. The number of defined daily dose per inhabitant and day of parenteral administration have decreased during the last years. CONCLUSIONS: Availability of new analgesic opioid drugs with better pharmacokinetic profiles has contributed to an increase of their consume in Spain.

[Safety of meningococcal A and C vaccine. Data from the Spanish drug surveillance system. Meningococcal Vaccine Research Group of the Spanish System of Drug Surveillance]. / Seguridad de la vacuna antimeningocócica A+C. Datos recogidos por el Sistema Español de Farmacovigilancia. Grupo de Investigación sobre la vacuna antimeningocócica del Sistema Español de Farmacogigilancia.

OBJECTIVE: Data on meningococcal vaccines safety are scanty. In 1997 several vaccination campaign took place in Spain. Thus, this situation was used to improve our knowledge about the safety profile of this vaccine. METHODS: An inquiry was carried out to the Regional Centers of the Spanish Pharmacovigilance System to know the number of vaccinated people and the type and number of suspected cases of adverse reactions. RESULTS: There were 133 identified cases of suspected adverse reactions associated with meningococcal A and C vaccine until June 1st, 1998. Most of them affected the skin (25,3%) or nervous system (similar proportion). Those of allergic reactions accounted for 35,2%. Two cases were considered as severe, although they were resolved without secuelae. CONCLUSIONS: Serious risks were not detected. The Spanish Pharmacosurveillance System as an epidemiological surveillance resource has been useful to know the safety problems associated with antimeningococcal vaccine in the community.

Under-reporting of adverse drug reactions. Estimate based on a spontaneous reporting scheme and a sentinel system.

OBJECTIVE: Spontaneous reporting is the most common method used in pharmacovigilance and the best one to generate signals on new or rare adverse drug reactions (ADRs). Under-reporting is a major drawback of this system. The objective of this study was to quantify the extent of under-reporting in general practice and to assess the factors which influence it. METHODS: Details of ADRs collected through a short intensive survey were compared with primary care spontaneous reports received by the Castilla y Leon Regional Pharmacovigilance Centre during a 12-month reference period. The survey was undertaken by a random sample of 146 general practitioners (GPs), providing care to 149,487 people. The pharmacovigilance centre received reports concerning the whole regional population (2.5 million) covered by primary health care. The under-reporting coefficient (U) was estimated as the ratio between the number of effects observed by physicians in the survey and those spontaneously reported to the pharmacovigilance centre. RESULTS: The overall under-reporting rate was 1144 [95% confidence interval (CI): 928-1409]. Under-reporting was greater for psychiatric (2119; 945-4752) and gastrointestinal (1946; 1424-2659) disorders. Severe effects were more reported (U = 605; 151-2431) than moderate (863; 473-1575) and mild (1209; 973-1503) ones. The under-reporting rate was lower for drugs recently marketed (706; 406-1230) and slightly lower for unlabelled effects (1031; 641-1657). CONCLUSION: The under-reporting rate of ADRs is considerable, though not homogeneous for the different cases. This should be taken into account when comparing adverse effects (AEs) for different drugs. Under-reporting seems to be positively selective, as it involves mainly the less severe and better-known effects, preserving the value of spontaneous reporting for signal detection.

Monitoring treatment demand for drug abuse in Spain: perspective over a decade.

The Spanish Information System on Drug Abuse (SEIT) was established in 1987 by the National Plan on Drugs, based on three indirect indicators that reflect the health effects of drug use: treatment, emergency and mortality. The treatment indicator is the core of the system, the one with the best consolidation, higher coverage and greater quantity of reliable data accumulated. The configuration of the system has a regional basis (Autonomous Communities), which strongly influences its potentialities, operation, results, strengths and limitations. Only outpatient treatment admissions, reported by ambulatory treatment centres and prison units, are recorded. Double counting is eliminated at the regional level. Over a decade of existence, the SEIT, and mainly its treatment indicator, has proven to be an excellent tool for public health action, planning and decision making, as well as for research and co-operation between regions.

[Anti-ulcer drug consumption in Spain]. / Consumo de fármacos antiulcerosos en España.

OBJECTIVE: To check whether therapy to eradicate Helicobacter pylori has succeeded in reducing the consumption of traditional ulcer medication. DESIGN: A longitudinal, retrospective study of the use of medication. SETTING: Spain in the decade from 1988 to 1997. PARTICIPANTS: Pharmaceutical products belonging to the anatomical therapeutic group AO2B (for ulcers) and dispensed at the Social Security's expense. MEASUREMENTS AND MAIN RESULTS: Despite the widespread use of treatments to eradicate H. pylori, it was found that consumption of ulcer medication continued to increase markedly, from 5 daily doses per 1000 inhabitants in 1988 to 19 in 1997. In 1997 the two most frequently taken active principles in the group were omeprazole and ranitidine. Drugs indicated for gastric protection were also used much more. However, in absolute values, they stayed well below anti-H2 drugs and proton pump inhibitors. CONCLUSION: The introduction into Spain of therapy to eradicate H. pylori has failed to reduce the use of ulcer medication. The use of anti-H2 drugs and proton pump inhibitors for gastric protection may explain a part of the increase in consumption experienced by these two pharmacological groups.

Is metronidazole teratogenic? A meta-analysis.

AIM: In order to assess whether the use of metronidazole during pregnancy is associated with a higher risk of congenital malformations, a meta-analysis was conducted. METHODS: All epidemiological studies (cohort and case-control) which estimate risk of congenital malformations after exposure to metronidazole during early pregnancy were included in the meta-analysis. To obtain a summary odds ratio, the Mantel-Haenszel method was used. A test to verify absence of heterogeneity was also performed. RESULTS: One unpublished case-control and four published cohort studies fulfilled the inclusion criteria and were not statistically heterogeneous. A summary odds ratio was calculated for metronidazole exposure during the first trimester: OR = 1.08, 95% CI: 0.90-1.29, heterogeneity test chi2 = 4.72, P = 0.32. CONCLUSIONS: This meta-analysis did not find any relationship between metronidazole exposure during the first trimester of pregnancy and birth defects.