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ABSTRACT: INTRODUCTION: Bisphosphonates are used worldwide to treat osteoporosis and, thus, to prevent fractures. Though they have been proven in clinical trials to avoid some fractures, their effectiveness in reducing hip fractures is unclear. The aim of the present study was to explore the relationship between bisphosphonate use and hip fracture trends in Spain. METHODS: For this purpose, an ecologic study spanning 2002 to 2008 was conducted in Spain. Consumption data were obtained from the Spanish Ministry of Health and Social Policy. The number of hip fractures was obtained from hospital discharges; annual hip fracture rates were determined and standardized using the Spanish 2002 population census. A linear regression was performed between fracture rate and use of bisphosphonates; R (2) and Pearson correlation coefficient were calculated. RESULTS: From 2002 to 2008, dispensed prescriptions of bisphosphonates in Spain increased from 3.28 to 17.66 DDD/1,000 inhabitants per day. In the same period, the crude hip fracture rate increased from 2.85 to 3.02 cases per 1,000 inhabitants older than 50 years; however, when age standardized rates were estimated, the rate declined from 2.85 to 2.79. Analyzed by sex, the standardized rate for men slightly increased from 1.45 to 1.48, while for women the rate significantly dropped from 4.00 to 3.91. CONCLUSION: A small effect of bisphosphonates on hip fracture rates can not be ruled out; however, other factors might partially explain this decline. Assuming this medication was the only cause for hip fracture rate reduction, the elevated medication cost to avoid a single hip fracture makes it necessary to explore less expensive interventions.
European Journal of Clinical Pharmacology 07/2012; · 2.85 Impact Factor
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ABSTRACT: Prior to marketing of pandemic influenza vaccines, the only safety data were those from clinical trials. The objective of this study was to compare information coming from spontaneous reporting with that systematically collected in a formal observation study; this also permits to further evaluate safety of pandemic influenza vaccines in the targeted patients' population. Out of a sample of 507 vaccinated subjects, 103 (20.3%) developed some complication. In the same period 83 reports corresponding to all vaccinated people of Castilla y León (n=131,462) were collected. Severe cases were 1 (1%) and 7 (8.4%), respectively, with the two procedures. The spontaneous reporting rate was 322-fold lower than that identified through the follow-up study; when considered the severe cases, it was 37-fold lower. Under certain circumstances reporting might be performing better than usual due to strengthening of the surveillance system. Adverse events observed for the pandemic H1N1 vaccines lie within the expected safety profile for common events with influenza vaccines. An overall benefit-risk assessment of these vaccines should be done.
Vaccine 01/2011; 29(3):519-22. · 3.77 Impact Factor
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A Carvajal,
D Macías,
I Salado,
M Sáinz,
S Ortega,
C Campo,
J García del Pozo,
L H Martín Arias,
A Velasco,
S Gonçalves,
R Pombal,
R Carmona
Clinical Pharmacology & Therapeutics 10/2009; · 6.04 Impact Factor
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A Carvajal,
D Mac|[iacute]|as,
I Salado,
M S|[aacute]|inz,
S Ortega,
C Campo,
J Garc|[iacute]|a del Pozo,
LH Mart|[iacute]|n Arias,
A Velasco,
S Gon|[ccedil]|alves,
R Pombal,
R Carmona
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ABSTRACT: We searched the Spanish and Portuguese pharmacovigilance databases for spontaneous case reports of heart rhythm disturbances associated with rupatadine and other new H1 antihistamines. Five cases were found involving patients treated with rupatadine (13.9% of all reports relating to this drug). In all five cases, the reaction started after exposure and resolved when the drug was discontinued. In two cases, rupatadine was the only medication being taken by the patient, and no other condition that could explain the heart rhythm disturbances was diagnosed. The reporting odds ratio was 3.2 (95% confidence interval, 1.0–10.5). The reporting rate was 2 cases per 100,000 patients treated per year (95% confidence interval, 0.4–6.0). These results suggest a causal relationship between rupatadine and heart rhythm disturbances.
Clinical Pharmacology & Therapeutics 02/2009; 85(5):481-484. · 6.04 Impact Factor
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A Carvajal,
D Macías,
I Salado,
M Sáinz,
S Ortega,
C Campo,
J García del Pozo,
L H Martín Arias,
A Velasco,
S Gonçalves,
R Pombal,
R Carmona
[show abstract]
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ABSTRACT: We searched the Spanish and Portuguese pharmacovigilance databases for spontaneous case reports of heart rhythm disturbances associated with rupatadine and other new H1 antihistamines. Five cases were found involving patients treated with rupatadine (13.9% of all reports relating to this drug). In all five cases, the reaction started after exposure and resolved when the drug was discontinued. In two cases, rupatadine was the only medication being taken by the patient, and no other condition that could explain the heart rhythm disturbances was diagnosed. The reporting odds ratio was 3.2 (95% confidence interval, 1.0-10.5). The reporting rate was 2 cases per 100,000 patients treated per year (95% confidence interval, 0.4-6.0). These results suggest a causal relationship between rupatadine and heart rhythm disturbances.
Clinical Pharmacology & Therapeutics 02/2009; 85(5):481-4. · 6.04 Impact Factor
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ABSTRACT: New marketed antimigraine drugs (triptans) are promising in the management of migraine pain. The impact of these new drugs on the overall consumption of the antimigraine drugs merits an analysis.
The package units of antimigraine drugs, sold and reimbursed by the Spanish National Health System, are used for estimations. Data are presented as defined daily doses per 10,000 inhabitants/day.
During the 1990-2000 period, antimigraine drug utilization as a whole decreased by more than 25%; triptan use increased while ergot alkaloids' declined.
The pattern of antimigraine drug utilization in Spain has changed noticeably in accordance with recent recommendations.
Acta Neurologica Scandinavica 03/2003; 107(2):158-60. · 2.47 Impact Factor
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Medicina Clínica 02/2001; 116(3):117. · 1.38 Impact Factor
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ABSTRACT: A meta-analysis was conducted to estimate the difference of weight loss among patients treated with placebo and with fenfluramine or dexfenfluramine after 1, 2, 3, 6, and 12 months of treatment. Placebo-controlled, double-blind, randomized clinical trials, whose results were presented as weight loss by the placebo group and the drug-treated patient group, were selected for the analysis. For the pooled estimations, the method of the weighted means by the inverse of the variance was used. The association between the difference of means and several predictive variables was studied by means of weighted linear regression. Patients treated with fenfluramine or dexfenfluramine achieved a higher weight loss than those receiving placebo in all the periods studied. The greatest efficacy was observed after 3 months of treatment. Beyond this time, there is a decline in the effectiveness. Based on the efficacy data, treatments longer than 3 months would not be justified.
Methods and Findings in Experimental and Clinical Pharmacology 07/2000; 22(5):285-90. · 0.93 Impact Factor
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ABSTRACT: A study of the effect of nicorandil (N-2-(hydroxyethyl)nicotinamide nitrate, CAS 65141-46-0), a potassium channel and guanylatecyclase activator, upon preparations of rat was deferens and uterus, and guinea pig ileum was performed. Nicorandil does not modify rat isolated was deferens responses to noradrenaline (norepinephrine) and potassium. The drug exerts a non-competitive antagonist effect upon rat isolated uterus response to serotonin, histamine, oxytocin, and, at high concentrations, inhibits guinea-pig isolated ileum responses to acetylcholine, histamine, 4-aminopyridine and potassium.
Arzneimittel-Forschung 05/2000; 50(4):341-4. · 0.72 Impact Factor
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ABSTRACT: To investigate the impact of new regulatory measures on opioid consumption in Spain during the period 1985-1998.
A search in the ECOM (Especialidades Consumo de Medicamentos) database of the Ministry of Health was made for the 1985-1998 period. This database contains information about drug preparations prescribed in primary care in the National Health System in Spain.
Since 1985-1998, the overall opioid consumption has increased tenfold, from 94.7 DDD (defined daily dose) per million inhabitants per day to more than 1000 DDD. For the five drugs that require a special prescription form (morphine, methadone, pethidine, tilidine and fentanyl), the consumption has increased 13.5-fold.
A huge increase in opioid consumption has occurred. In this increase, changes in supply and, to a lesser extent, regulatory measures have played an important role.
European Journal of Clinical Pharmacology 12/1999; 55(9):681-3. · 2.85 Impact Factor
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ABSTRACT: A study was undertaken to know better the effects of venlafaxine hydrochloride on the responses of isolated rat vas deferens to noradrenaline and dopamine, those of isolated rat uterus to serotonin and histamine, and those of isolated guinea-pig ileum to acetylcholine and histamine. Venlafaxine hydrochloride increased the response of rat vas deferens to noradrenaline but not to dopamine. Venlafaxine did not alter the response of rat isolated uterus to serotonin. In rat uterus, venlafaxine did not modify the response to histamine but was able to increase it in guinea-pig ileum. An anticholinergic effect was observed with the lowest concentration tested. Although venlafaxine is a selective serotonine reuptake inhibitor in the central nervous system, serotonin uptake was not seen in the rat uterus. The anticholinergic effects observed in the present study might be consistent with some of the side-effects associated with venlafaxine.
Journal of Autonomic Pharmacology 05/1999; 19(2):109-13.
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ABSTRACT: To check whether therapy to eradicate Helicobacter pylori has succeeded in reducing the consumption of traditional ulcer medication.
A longitudinal, retrospective study of the use of medication.
Spain in the decade from 1988 to 1997.
Pharmaceutical products belonging to the anatomical therapeutic group AO2B (for ulcers) and dispensed at the Social Security's expense.
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.
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.
Atención Primaria 04/1999; 23(4):218-21. · 0.63 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
European Journal of Clinical Pharmacology 09/1998; 54(6):483-8. · 2.85 Impact Factor
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ABSTRACT: 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.
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.
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.
Availability of new analgesic opioid drugs with better pharmacokinetic profiles has contributed to an increase of their consume in Spain.
Medicina Clínica 10/1997; 109(8):281-3. · 1.38 Impact Factor
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ABSTRACT: 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.
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.
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.
This meta-analysis did not find any relationship between metronidazole exposure during the first trimester of pregnancy and birth defects.
British Journal of Clinical Pharmacology 09/1997; 44(2):179-82. · 2.96 Impact Factor
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ABSTRACT: 1. Fluoxetine and fluvoxamine reinforced the response to norepinephrine of isolated rat vas deferens incubated in Krebs-Henseleit solution. 2. This reinforcement disappeared when cocaine, 17 beta-estradiol, and propranolol were added to the incubation medium. 3. Fluoxetine and fluvoxamine did not have antimuscarinic effect, but they did have antihistaminic effect, and at high concentrations they inhibited the contraction induced by potassium ion on the isolated rat uterus preparation (IC50 3.99 x 10(-6) and 1.82 x 10(-5) M, respectively).
General Pharmacology 05/1997; 28(4):509-12.
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ABSTRACT: 1. 4-Aminopyridine and 3,4-diaminopyridine produced concentration-dependent contraction on guinea-pig isolated ileum incubated in Tyrode solution. The EC30 values were 1.14 x 10(-4) and 1.39 x 10(-4) M, respectively. 2. Calcium channel blockers such as verapamil, diltiazem, nifedipine, flunarizine, and lanthanum chloride antagonized the contracting effect induced by 4-aminopyridine and 3,4-diaminopyridine in guinea-pig isolated ileum. 3. Diazoxide and atropine sulphate behaved similarly as antagonists of the contracting effect induced by 4-aminopyridine and 3,4-diaminopyridine in guinea-pig isolated ileum. 4. It is concluded that the aminopyridines exert their effects through the release of acetylcholine from parasympathetic nerve terminals.
Journal of Autonomic Pharmacology 03/1997; 17(1):53-7.
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ABSTRACT: Imipramine-N-oxide, quinupramine, clomipramine, doxepin, maprotiline, amineptine, amoxapine, mianserin, minaprine, nomifensine, viloxacine, trazodone and lofepramine effects were studied on rat vas deferens responses to noradrenaline. Tissues were prepared in Krebs-Henseleit solution with and without adding cocaine. 17 beta-estradiol and propranolol for blocking neuronal and extraneuronal noradrenaline reuptake. In normal Krebs-Henseleit solution imipramine-N-oxide, nomifensine, viloxacine and lofepramine increased noradrenaline responses, while clomipramine, trazodone and doxepin behaved as competitive antagonists. When adding cocaine, 17 beta-estradiol and propranolol to the solution there was antagonism but no increase in responses.
Methods and Findings in Experimental and Clinical Pharmacology 11/1996; 18(8):507-11. · 0.93 Impact Factor
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ABSTRACT: 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.
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.
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).
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.
Medicina Clínica 06/1996; 106(17):649-52. · 1.38 Impact Factor
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ABSTRACT: 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.
Journal of Clinical Epidemiology 03/1996; 49(2):255-61. · 4.27 Impact Factor
