Impact of regulatory measures on antipsychotics drug consumption in Castilla y León, Spain.

OBJECTIVES: Antipsychotics are currently used to treat different diseases; even some off-labelled conditions are treated with this medication. Consumption and cost of antipsychotic drugs sharply increased in Spain after second-generation drugs were marketed; several regulatory measures were adopted to curb this trend. The aim of this study was to examine the impact of these measures upon the use and cost of antipsychotics. STUDY DESIGN: Study of drug use (SDU) from 1995 to 2012. Consumption and cost data were obtained from the CONCYLIA database; this database contains the retail community pharmacies sales of medicinal products reimbursed by the National Health System in Castilla y León (Spain). METHODS: Data are presented as defined daily doses per 1000 inhabitants per day (DID) and day treatment cost (DTC). RESULTS: First-generation antipsychotics prescriptions gradually decreased from 3.0 to 1.8 DID; meanwhile, prescriptions for second-generation antipsychotics considerably increased from 0.3 to 9.9 DID. The use of risperidone dropped after the marketing of its structural derivative paliperidone with a similar efficacy but with a substantially higher cost per day. In 2011 and thereafter, patients in Spain began to pay a part of the medications cost, but this did not decrease antipsychotics consumption. Global cost of antipsychotics only began to fall after measures were adopted to lower the price of medicines because of the economic collapse in Spain after May 2010. CONCLUSION: Several health policy measures have tried to reduce antipsychotics consumption in Spain, special ways of dispensing, marketing of generic drugs and special economic measures for patients. These measures eventually failed to avoid the increase in antipsychotics use. The cost only dropped when lowering prescription drug prices took place.

Risk of bursitis and other injuries and dysfunctions of the shoulder following vaccinations.

While vaccination injection site adverse reactions are usually mild and transient in nature, several cases of bursitis and other shoulder injuries have been reported in the medical literature. However, these lesions are not included in vaccine label inserts. To identify the characteristics of post-vaccination shoulder injuries and those of patients and involved vaccines, as well as their potential causes, a systematic review of the cases of vaccination-related bursitis and other shoulder injuries reported in the literature and notified to the Spanish Pharmacovigilance System database (FEDRA) have been conducted. We found 45 cases of bursitis and other shoulder injuries that appeared following the vaccine intramuscular injection given into the deltoid muscle (37 from the systematic review of the literature, and 8 from the scrutiny in the Spanish Pharmacovigilance System database, FEDRA). All the patients were adult, 71.1% females, with a mean and median age of 53.6years (range: 22-89). The most frequently involved vaccines were influenza and pneumococcal vaccines, respectively; followed by diphtheria-tetanus-pertussis, diphtheria-tetanus toxoid, human papillomavirus, and hepatitis A vaccines. The most frequent shoulder lesion was bursitis. Most of patients required medical care due to severe local pain and arm mobility restriction. In a majority of cases, symptoms started 48h post vaccination. Subdeltoid or subacromial bursitis and other shoulder lesions may be more common than suspected. Such lesions predominantly affect women. The cause may be related to antigens or adjuvants contained in the vaccines that would trigger an immune or inflammatory response. However, they are more likely to be the consequence of a poor injection technique (site, angle, needle size, and failure to take into account patient's characteristics, i. e., sex, body weight, and physical constitution). Therefore, vaccination-related shoulder injuries would be amenable to prevention.

Guillain-Barré syndrome and influenza vaccines: A meta-analysis.

Cases of Guillain-Barré syndrome (GBS) have been occasionally associated with influenza vaccines; this possible risk, even if rare, is a matter of much concern. To investigate the strength of this association, a systematic review and a meta-analysis have been conducted; for the purpose, controlled observational studies addressing the risk of GBS associated with different influenza vaccines were sought. We finally selected 39 studies of interest published between 1981 and 2014 (seasonal influenza vaccines, 22; pandemic influenza vaccines, 16; both vaccines simultaneously administered, 1); funnel plot did not identify publication bias. At the association between any influenza vaccine - whether seasonal or pandemic - with GBS, the overall relative risk was 1.41 (95% CI, 1.20-1.66). Pandemic vaccines presented a higher risk (RR=1.84; 95% CI, 1.36-2.50) compared to seasonal vaccines (RR=1.22; 95% CI, 1.01-1.48); the latter should be considered as marginally statistically significant. Pandemic adjuvanted vaccines were not found to be related to a higher risk compared to non-adjuvanted vaccines. The results of the present meta-analysis point to a small but statistically significant association between influenza vaccines, particularly the pandemic ones, and GBS, which is consistent with current explanations upon possible mechanisms for this condition to appear.

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.

[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.

Heart rhythm disturbances associated with rupatadine: a case series from the Spanish and Portuguese pharmacovigilance systems.

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.

Age-related changes in contractile responses to noradrenaline in isolated blood vessels from rat and rabbit.

1. Age-related changes in vascular function have been studied using rat (1, 6 and 10 months) and rabbit (1 and 6 months) isolated aorta and rat (1, 6 and 10 months) mesenteric perfused artery. 2. The EC50 values of noradrenaline in rat aorta increased with age. Similarly, contractile response to noradrenaline (10(-6) M) and potassium (80 mM) increased with age. In rabbit aorta, contractile responses, both for noradrenaline and potassium, decreased with age. No changes were observed with age in sensitivity to noradrenaline in rat mesenteric perfused artery. 3. The results of the present study suggest that age-related changes may be different for different blood vessels. The sensitivity decrease to noradrenaline in rat aorta involved postreceptor mechanisms.

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.

Opioid consumption in Spain--the significance of a regulatory measure.

OBJECTIVE: To investigate the impact of new regulatory measures on opioid consumption in Spain during the period 1985-1998. METHODS: 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. RESULTS: 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. CONCLUSION: 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.