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Introduction Antipsychotic drugs (APDs) are used to treat several mental illnesses. Some APDs have long been known to be associated with QT prolongation, potentially leading to torsades de pointes (TdP) and sudden cardiac death (SCD). In 2005, thioridazine was withdrawn because of the risk of SCD, bringing further attention to the arrhythmogenic potential of APDs. Aim The aim of the current study was to evaluate the use of APDs in five European countries during the years 1996-2010. Methods A cohort study was conducted using prescription/dispensing data from seven healthcare databases [the AARHUS University Hospital Database (Denmark), the German Pharmacoepidemiological Research Database (GePaRD) (Germany), Health Search Database/Thales (HSD) and Emilia Romagna Regional Database (ERD) (Italy), PHARMO Database Network and Integrated Primary Care Information (IPCI) (the Netherlands) and The Health Improvement Network (THIN) (the UK), covering a population of 27 million individuals. The annual prescription rate of APDs was measured overall and for individual medications. APDs were classified as torsadogenic according to the Arizona-CERT list. All analyses were stratified by age, gender and calendar year. Results A total of 559 276 person-years (PYs) of exposure to APDs was captured. The crude annual prescription rate of APD use ranged from 3.0/1000 PYs in ERD to 7.7/1000 PYs in AARHUS. Among APDs with established torsadogenic potential, thioridazine was the most frequently used medication in the UK. Haloperidol was commonly prescribed in Italy and the Netherlands. The use of APDs with torsadogenic potential was much higher in elderly patients. Conclusions Substantial use of APDs with torsadogenic potential has been reported in Europe in recent years, in spite of increasing concerns about their arrhythmogenic potential. This use was even greater in elderly patients, who are at higher risk of SCD. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • In the last years there has been a growing trend in anti-epileptic drug (AED) use, particularly in elderly patients, but few data concerning indication of use are available in general practice. • Various AEDs, including newer agents, have been approved for indications other than epilepsy and are increasingly also used for unlicensed indications. • No data about the impact of re-imbursement restrictions on the choice of anti-epileptic drugs in general practice are available. WHAT THIS STUDY ADDS • In general practice, a rapid increase of AED prescriptions in the elderly was observed, principally due to the use of newer AEDs for indications other than epilepsy. • Re-imbursement restrictions influenced newer AED use, particularly pregabalin and gabapentin prescriptions. • Phenobarbital, accounting for more than 50% of total AED volume, was the most prescribed medication during the entire study period. This finding should be considered in light of the potential risks associated with phenobarbital use in the geriatric population. AIMS The aims of the study were to assess the trend of older and newer anti-epileptic drugs (AEDs) in the elderly population and to analyze the effects of a health-policy intervention with regard to AED use in general practice in a setting in Southern Italy. METHODS Data were extracted from the 'Caserta-1' Local-Health-Unit Arianna database in the years 2004-07. Patients aged over 65 years, receiving at least one AED prescription and registered in the lists of 88 general practitioners, were selected. The use of older and newer AEDs was calculated as 1 year prevalence and incidence of use and defined daily dose (DDD) per 1000 inhabitants day−1. Sub-analyses by gender, age and indication of use were performed. RESULTS Most of AED users were treated because of neuropathic pain (64.8%). However, the main indication of use for older AEDs (57.8%) was epilepsy, whereas newer AEDs (79.5%) were used for neuropathic pain. Prevalence and incidence of newer AED use increased until 2006, followed by a reduction in 2007. Newer AEDs, particularly gabapentin and pregabalin, were used in the treatment of more patients than older AEDs. However phenobarbital, accounting for more than 50% of total AED volume, was the most prescribed medication during the entire study period. CONCLUSIONS An increasing use of AEDs has been observed during 2004-07, mostly due to the prescription of newer compounds for neuropathic pain. The fall in the use of newer AEDs during 2007 coincides with revised re-imbursement criteria for gabapentin and pregabalin. The large use of phenobarbital in the elderly should be considered in the light of a risk of adverse drug reactions. [ABSTRACT FROM AUTHOR]

Background: Energy drinks (ED) are a widely used group of beverages known for their stimulant effects on central nervous system (CNS). The main components of ED are caffeine, taurine, carbohydrates, glucuronolactone, inositol, niacin, pantenol, and β-complex vitamins. The studies evaluating the effects of ED describe improvements in attention and/or reaction times and indices of alertness. It has been also shown that combination of caffeine and glucose, fundamental constituents of ED, can ameliorate deficits in cognitive performance and subjective fatigue during extended periods of cognitive demand. Moreover, the associated ingestion of alcohol and ED has recently been observed to be becoming more and more widespread. Methods: With the aim to know the habits and uses of students, we administered a questionnaire containing questions regarding ED drinking alone or in association with alcoholic beverages. Five hundred students of the School of Medicine of the University of Messina were interviewed, and 450 filled the questionnaire. Results: A total of 56.9% of students declared using ED. A great part of users (48.4%) associate frequently ED and alcohol. In particular, 35.8% of ED + alcohol users have used ED + alcohol more than 3 times in the last month. Distinguishing the users into 2 groups (users of ED + alcohol and users of both ED and ED + alcohol), we observed in the second group a major use of cocktail containing a mix of ED and alcoholic beverages. This difference between the 2 groups is less represented about the ingestion of ED + alcohol in the night. Conclusions: Our data indicate that association of ED + alcohol is very popular among students. This behavior can be dangerous. In fact, the combination of ED + alcoholic drinks can reduce adversive symptoms of alcohol intoxication including the depressant effects. As consequence, users of ED + alcoholic beverages might not feel the signs of alcohol intoxication, thus increasing the probability of accidents and/or favoring the possibility of development of alcohol dependence. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 33-year-old woman who suffered hemorrhagic cystitis due to her intake of slimming herbal product. She underwent urinalysis and showed the presence of red blood cells but urinary track infection was not identified. The physician advised her to discontinue her intake of herbal product. It states that after three months, absence of red blood cells on the patient was found out. It says that some herbal products do not necessarily ensure safety.

Gynecomastia is characterized by benign progressive enlargement of the male breast. A pharmacologic origin is identified in 10-20% of cases. Several case reports have associated this condition to the use of statins. However, to our knowledge, no case of rosuvastatin-induced gynecomastia has been reported in the literature. We describe a 57-year-old man who developed bilateral gynecomastia after 2 months of rosuvastatin therapy. After switching to a different statin, atorvastatin, his symptoms resolved within 1 month. Use of the Naranjo adverse drug reaction probability scale indicated a possible relationship between the patient's development of gynecomastia and rosuvastatin therapy. The relatively strong effect of rosuvastatin on inhibiting steroidogenesis might have explained why our patient's gynecomastia occurred only with this agent. Clinicians should be aware of the possibility of adverse endocrine reactions when statins are prescribed, including newer agents such as rosuvastatin. [ABSTRACT FROM AUTHOR]

Aim: Coffee intake is common during pregnancy. However, the influence of coffee and caffeine on pregnancy has not yet been fully determined. Some studies show that high coffee intake could cause miscarriage, preterm birth or reduction of fetal growth, but other studies do not support these findings. The aim of the present study was to analyze data collected from a database focusing on coffee intake during pregnancy, which was specifically created for multicenter studies carried out in the maternity units of Italian general hospitals. Principal outcomes of pregnancy during pregnancy were considered. Methods: Data of 5405 pregnancies were collected by a direct questionnaire supplemented with data from patients'clinical records during the survey named PHYTO.VIG.GEST. Results: We observed that 42.3% of the total sample had consumed at least one coffee a day during pregnancy. Analysis of a dose–response relationship showed that, in pregnant women starting from the consumption of three coffees a day (6% of pregnant women consuming coffee), there is a statistically significant association between number of coffees and reduction of babies birth weight (< 2500 g). Coclusion: Even though high coffee intake is known to influence negatively birth weight, our results indicate that a significant percentage of pregnant women maintain this habit. [ABSTRACT FROM AUTHOR]

An abstract of the article "A Case of Atrial Fibrillation Induced by Inhaled Fluticasone Propionate," by Alessandro Oteri and colleagues is presented.

A letter to the editor is presented about reversible acute hepatitis induced by rosuvastatin.

Background: There are conflicting findings from observational studies of the arrhythrogenic potential of azithromycin. Our aim was to quantify the association between azithromycin use and the risk of ventricular arrhythmia.Methods: We conducted a nested case-control study within a cohort of new antibiotic users identified from a network of 7 population-based health care databases in Denmark, Germany, Italy, the Netherlands and the United Kingdom for the period 1997-2010. Up to 100 controls per case were selected and matched by age, sex and database. Recency of antibiotic use and type of drug (azithromycin was the exposure of interest) at the index date (occurrence of ventricular arrhythmia) were identified. We estimated the odds of ventricular arrhythmia associated with current azithromycin use relative to current amoxicillin use or nonuse of antibiotics (≥ 365 d without antibiotic exposure) using conditional logistic regression, adjusting for confounders.Results: We identified 14 040 688 new antibiotic users who met the inclusion criteria. Ventricular arrhythmia developed in 12 874, of whom 30 were current azithromycin users. The mean age of the cases and controls was 63 years, and two-thirds were male. In the pooled data analyses across databases, azithromycin use was associated with an increased risk of ventricular arrhythmia relative to nonuse of antibiotics (adjusted odds ratio [OR] 1.97, 95% confidence interval [CI] 1.35-2.86). This increased risk disappeared when current amoxicillin use was the comparator (adjusted OR 0.90, 95% CI 0.48-1.71). Database-specific estimates and meta-analysis confirmed results from the pooled data analysis.Interpretation: Current azithromycin use was associated with an increased risk of ventricular arrhythmia when compared with nonuse of antibiotics, but not when compared with current amoxicillin use. The decreased risk with an active comparator suggests significant confounding by indication. [ABSTRACT FROM AUTHOR]

Purpose: The study aims to analyse overall as well as subgroup-specific outpatient paediatric macrolide use in five European countries, including time trends of macrolide prescription rates, and to provide potential targets for future interventions aiming to promote judicious macrolide use. Methods: Macrolide prescription rates per 1000 person years to paediatric outpatients (≤18 years) were calculated using healthcare databases from Denmark, Germany, Italy, The Netherlands and the UK. Poisson regression analysis was used to estimate the influence of increasing calendar year on total macrolide and subgroup-specific prescription rates based on monthly data, adjusted for seasonal variations. Time periods for which data were available varied between 4 (Italy 2007-10, Germany 2005-8) and 10 years (UK 2000-9). Results: Paediatric macrolide use in 2008 varied between 199 (Italy) and 47 (Netherlands) prescriptions per 1000 person years. Prescription rates of short-acting macrolides declined significantly in all countries but the UK. The use of intermediate-acting macrolides significantly rose with increasing calendar year in Denmark (rate ratio (RR) = 1.12) and the UK (RR = 1.06), but decreased in Germany (RR = 0.84) and The Netherlands (RR = 0.97). Prescription rates of long-acting agents increased in Denmark (RR = 1.05), The Netherlands (RR = 1.05) and the UK (RR = 1.11) (all trends p < 0.05). The greatest seasonal variations of macrolide use between summer and winter months were observed in Italy and Germany. Conclusions: The observed trend toward increased prescribing of intermediate- and/or long-acting agents might further increase resistance pressure on bacterial pathogens due to their prolonged plasma half-life and broader antibacterial activity. Marked seasonality of prescription rates in the high-utilising countries, Italy and Germany, suggests frequent prescription of macrolides to treat respiratory infections which may be of viral origin. [ABSTRACT FROM AUTHOR]

Background: Acute liver failure is idiopathic and drug-related in, respectively, around 50 and 15 % of children. Population-based, epidemiologic data about the pattern of disease manifestation and incidence of less severe acute liver injury, either idiopathic or potentially drug-attributed are limited in children and adolescents. Objectives: (i) To assess the incidence of idiopathic acute liver injury (ALI) and its clinical features in children and adolescent outpatients; and (ii) to investigate the role of the drug as a potential cause of ALI which is considered idiopathic. Methods: A retrospective cohort study was performed during the years 2000-2008. Data were retrieved from three longitudinal electronic healthcare databases in two European countries: Pedianet and Health Search/CSD Longitudinal Patient Database from Italy and the Integrated Primary Care Information database from The Netherlands. Cases of idiopathic acute liver injury in population aged <18 years were identified by exclusion of all competing causes of liver injury (e.g. viral, autoimmune hepatitis), according to CIOMS criteria. The potential role of drug exposure as actual underlying cause of idiopathic ALI was detected through signal detection mining techniques. Both pooled and country-specific incidence rates [IR/100,000 person-years (PYs)] of idiopathic ALI and pooled adjusted rate ratios (RR) of drugs identified as a potential cause of idiopathic ALI, plus 95 % confidence intervals (CI) were estimated using the custom-built software Jerboa. Results: Among 785 definite cases of idiopathic ALI, the pooled IR was 62.4/100,000 PYs (95 % CI 58.1-66.8). The country-specific IR was higher in Italy (73.0/100,000 PYs, 95 % CI 67.8-78.4) than in The Netherlands (21.0/100,000 PYs, 95 % CI 16.0-27.2) and increased with age in both countries. Isolated elevations of liver enzymes were reported in around two-thirds of cases in Italy, while in The Netherlands the cases were more often identified by a combination of signs/symptoms. Among drugs detected as potential underlying cause of idiopathic ALI, clarithromycin (RR 25.9, 95 % CI 13.4-50), amoxicillin/clavulanic acid (RR 18.6, 95 % CI 11.3-30.6), and amoxicillin (RR 7.5, 95 % CI 3.4-16.8) were associated with the highest risk compared to non-use. Conclusion: The incidence of idiopathic ALI in paediatrics is relatively low and comparable with adults. Clinical presentations differ between the two European countries. Signal detection in healthcare databases allowed identifying antibiotics as the drugs mostly associated with ALI with apparently unknown aetiology. [ABSTRACT FROM AUTHOR]

Aim In the last decade, new glucose lowering drugs ( GLDs) have been launched, and also several warnings regarding their safety. The cardiovascular safety of thiazolidinediones ( TZD) has been questioned. We analyzed the prescription pattern of GLDs from 2000 to November 2009 in the United Kingdom ( UK) using the THIN database with special focus on the effects of the safety warnings about rosiglitazone issued in May 2007 and January 2008. Methods Annual prevalence and incidence of GLD prescriptions were measured. For TZD, the monthly prevalence and incidence of prescription were calculated from May 2006 to January 2009. The switching pattern around the FDA alert and the characteristics of subjects starting treatment with TZD before and after the alerts were observed. Results The prevalence of prescriptions of GLDs increased during the 10 year period, metformin increasing more than three times. Rosiglitazone prevalence showed an increased trend until May 2007, (2.3/1000 person-years) and decreased thereafter ( January 2009: 1.1/1000 person-years). The use of pioglitazone increased surpassing rosiglitazone from April 2008 onwards. The incidence of rosiglitazone use decreased sharply after May 2007 (0.8/1000 person-years). The prevalence of use of other therapies remained rather stable from 2000 to 2007 but increased afterwards. After May 2007, rosiglitazone users were increasingly switched to pioglitazone. There was an increased proportion of new users of pioglitazone with cardiovascular risk after the alerts. Conclusions The prescription of GLDs in the UK has increased in the last decade. For TZDs, it changed after May 2007 as well as the characteristics of the subjects treated with them. [ABSTRACT FROM AUTHOR]

Background: The Internet may play a crucial role in the prompt provision of updated drug safety information. Nevertheless, limited knowledge of the English language among healthcare professionals or suboptimal search skills constitute barriers to widespread and appropriate use of the Internet for this purpose in Italy. In order to provide accurate information on drug safety and to promote the reporting of adverse drug reactions, in 1999 the clinical section of the Italian Society of Pharmacology created the website www.farmacovigilanza.org, financially supported by a non-profit foundation. The website promptly and independently provides news published in the international literature on drug safety, translated into Italian. The site also contains specific sections dedicated to adverse reactions to herbal products and cosmetic preparations.Objectives: The aim of this paper was to describe the number and characteristics of users and the most intensively visited sections of the website. Furthermore, in September 2006, 300 registered users who had accessed a registered users area aimed specifically at health professionals more than 20 times in the preceding 12 months received a ten-item multiple choice questionnaire via e-mail, to assess satisfaction with the accuracy and promptness of information provided, text comprehension and other information sources for drug-related issues. We hereby describe the results of the survey, after careful analysis of the questionnaires.Results: Up until July 2007, the site had over 600 000 direct accesses and 9760 healthcare professionals registered to use the site. A total of 108 responses to the e-mailed questionnaire were received (response rate = 36%), of which 103 were analysed; five were excluded due to missing information. Overall, the majority of responders judged the information on the site as objective and understandable. More than 85% of participants declared that the site has influenced their opinion and attitudes toward the safety of medicines. In particular, responders said that they pay more attention to drug interactions and to the safety profile of newly marketed drugs, and spend more time on communicating the risks of drugs used by their patients. Specifically, responders stated that they pay more attention to drug interactions (87.7%), newly marketed drugs (68.5%), herbal remedies (56.2%), drugs in patients at increased risk (42.5%), drugs in pregnant women (42.5%) and cosmetics (13.7%).Conclusions: The website www.farmacovigilanza.org appears to be an effective tool that provides users of the site with independent, relevant and reliable safety information. It was found to influence (and possibly improve) the quality of prescribing of a large proportion of the general practitioners who responded to our questionnaire, and our results indicate a high appreciation of the information found on the website. Moreover, the survey disclosed that there is a substantial need for such information in the national language by healthcare professionals. We think that our approach can serve as a model for similar initiatives in countries elsewhere in the world. [ABSTRACT FROM AUTHOR]