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Aims: Human papilloma virus (HPV) is 1 of the most common sexually transmitted infection responsible for different types of cancer: cervical, penile, vulvar, anal and oropharyngeal. It can affect both males and females. Our aim was to enrich the knowledge on the safety profiles of HPV vaccines in the male population. Methods: We reviewed all the reports of adverse events following immunization (AEFI) present in the US Vaccine Adverse Event Reporting System from 1 January 2006 to 30 September 2018. Statistical data mining was performed using the reporting odds ratio with 95% confidence interval in order to detect disproportionality in reporting. Results: A total of 5493 reports of AEFI were retrieved. The events most reported and that proportionally occurred more frequently with HPV vaccines than with others in males were: syncope (n = 701, reporting odds ratio = 2.85, 95% confidence interval [1.41–5.76p), loss of consciousness (n = 425, 2.79 [1.36–5.72]) and fall (n = 272, 3.54 [2.00–6.26]). Conclusion: Most of the AEFIs were already reported in premarketing clinical trials and acknowledged for the corresponding vaccines. A disproportionate reporting was found for some of these events including syncope. The HPV vaccines are generally well tolerated in males, although limitations own of spontaneous reporting should be considered.

Little is known about the administration of direct-acting oral anticoagulants (DOACs) and the occurrence of alopecia. Our aim was to analyse the reports of alopecia following DOAC administration received until 2 May 2018 from VigiBase, the World Health Organization database. A descriptive analysis of age, sex, seriousness and dechallenge/rechallenge outcome was carried out. For each report, the time-to-onset was evaluated and the causality was assessed by using Naranjo algorithm. Overall, 1316 reports were retrieved, most concerning rivaroxaban (58.8%); 80% of the reports were related to females, in particular to those aged ≥65 years (23.1%). The median value of the time-to-onset was 28 days, with an interquartile range of 63 days. In 54.3% of the reports the causality was assessed as possible. In conclusion, a possible association could exist between DOACs administration and alopecia, but further observational studies are needed to confirm these findings.

Rotaviruses (RVs) are the most common cause of severe diarrheal disease. To date two rotavirus oral vaccines are licensed: Rotarix and Rotateq. Our aim was to contribute to the post-marketing evaluation of these vaccines safety profile. We collected all RV vaccines-related reports of Adverse Events Following Immunization (AEFI) in US Vaccine Adverse Events Reporting System (VAERS) and VigiBase between January 2007 and December 2017. A disproportionality analysis using Reporting Odds Ratio (ROR) was performed. A total of 17,750 reports in VAERS and 6,358 in VigiBase were retrieved. In VAERS, 86.2% of the reports concerned RotaTeq, whereas in VigiBase 67.7% of them involved Rotarix. Across the databases, diarrhea (1,672 events in VAERS, 1,961 in VigiBase) and vomiting (1,746 in VAERS, 1,508 in VigiBase) were the most reported AEFIs. Noteworthy, the RV vaccines-intussusception pair showed a ROR greater than 20 in both databases. Some new potential safety signals emerged such as fontanelle bulging, hypotonic-hyporesponsive episode, livedo reticularis, and opisthotonus. Overall, our data show that most of the reported AEFIs are listed in the Summary of Product Characteristics (SPCs). However, there remains the need to investigate the potential safety signals arose from this analysis, in order to complete the description of the AEFIs.

Background: Disseminated intravascular coagulation (DIC) occurs in several clinical conditions, including drug therapy. We aim to investigate the association between the administration of several drug classes and the onset of DIC by using the reports of Adverse Drug Reactions (ADR) collected in Vigibase, the World Health Organization (WHO) database of ADR. Methods: We collected reports of drug-related DIC from 1968 to September 2015, classified in Vigibase according to the MedDRA (Medical Dictionary for Regulatory Activities) term “Disseminated intravascular coagulation”. A disproportionality analysis using Reporting Odds Ratio (ROR) with 95% Confidence Interval (CI95%) was performed. Results: Overall, 4653 reports of drug-associated DIC were retrieved and the 75.9% of them was serious according to WHO seriousness criteria. DIC was significantly (ROR > 1, lower limit of CI95% > 1) associated with 88 drugs, mainly antineoplastic agents, antithrombotic agents and antibacterials for systemic use. Among of the most frequently reported individual drugs we found dabigatran (94 reports) ROR = 1.34 (CI95% 1.08–1.67), oxaliplatin and bevacizumab both with 75 reports and ROR = 1.77 (1.38–2.27) and 2.02 (1.57–2.61), respectively. Conclusion: A substantial number of drugs, widely used in the clinical practice, may be associated with the potential occurrence of DIC. For many of these drugs, the ADR is not acknowledged in the corresponding Summary of Product Characteristics. The high number of drugs involved underlines the importance of evaluate this condition such as an ADR that might occur during drug therapy.

Background: Antimicrobials resistance (AMR) is an increasingly serious global health problem, both in terms of clinical implications and economic expenditure. In Italy, there are differences in prescribing rates between regions. We aimed to compare these differences in two Italian provinces: one of Emilia Romagna (north region) and one of Puglia (south region). Methods: The number of antibiotics prescribed packages and the relative expenditure data (year 2015) were obtained. We applied the prescription quality indicators proposed by the European Surveillance of Antimicrobial Consumption for an in-depth analysis. Results: Both consumption and expenditure were higher in the south province. In the Apulian province also the use of parenteral antibiotics was more frequent. The most prescribed antibiotics in both the provinces were: penicillins (combined or not), macrolides, and fluoroquinolones. Conclusion: We observed variability between the north and south province in terms of antibiotics prescription. Overall, our study indicates that antibacterials could be overprescribed. The choice of the right antibiotic continues to be a demanding task for practitioners and much still needs to be done in the fight against AMR, starting from a more appropriate use and interventions aimed at raising awareness of antibiotic resistance.

Background: In July 2012 a new European legislation (Directive 2010/84/EU and Regulation No. 1235/2010) regarding pharmacovigilance has become effective. It has boosted the activity of Signal Detection through a monthly analysis of potential safety signals on EudraVigilance (EV). Our aim is to describe the procedure of signal detection on EV data and to present results obtained by the our pharmacovigilance centre. Method: Data are extracted from EV database, which collects suspected Adverse Drug Reactions (ADRs) of medicinal products in Europe. We are appointed to supervise digoxin, nicardipine, delapril, manidipine and hydrochlorothiazide/ramipril. ADRs are coded through MedDRA Preferred Terms and collected in the electronic Reaction Monitoring Report (eRMR). Statistical analysis is based on the Proportional Reporting Ratio (PRR) as a measure of disproportionality. Results: Up to April 2016 we have analyzed 45 eRMR for each drug. Two signals for nicardipine were submitted to the Pharmacovigilance Risk Assessment Committee of European Medicines Agency (EMA): acute pulmonary oedema (off-label use as tocolytic) and thrombocytopenia. Conclusions: Our experience shows the scientific and regulatory value of signal detection activity on EV data in order to continuously evaluate the benefit/risk profile of recent and older drugs.

Objectives To describe antibacterial prescribing patterns in outpatients aged 0–5 years from 2007 to 2013 in the Emilia-Romagna region, assessing sex- and age-specific consumption over time. Methods All children aged 0–5 years resident in the Emilia-Romagna region who received at least one prescription of a systemic antibacterial in the period 2007–13 were enrolled. The prescriptions of systemic antibacterials to children were collected from the regional prescription database. Data were stratified by year, sex and age, and analysed in terms of periodic prevalence and of annual prescription rate per 1000 person-years. Results The prevalence of children receiving at least one prescription per year varied from 68.0% in 2007 to 59.0% in 2013, while the average prevalence of children receiving five or more prescriptions per year was 6.96%. The annual prescription rate varied from 1621.26 in 2007 to 1372.27 in 2013. Penicillins + β-lactamase inhibitors accounted for 35.3% of total prescriptions, followed by extended-spectrum penicillins (28.6%), macrolides (17.0%) and third-generation cephalosporins (13.9%). Conclusions Despite recommendations, a significant overprescription of antibacterials to children still exists, showing no satisfactory improvements over the years. In contrast to Northern European countries, adherence to evidence-based guidelines was poor, with frequent prescribing of broad-spectrum agents for the treatment of mostly viral childhood infectious disease.

Introduction The cardiovascular safety profile of macrolides and fluoroquinolones has been widely discussed. The aim of the present study is to provide the contribution of real-world data onto the ongoing discussion about cardiovascular toxicity of both macrolides and fluoroquinolones. Methods Reports of adverse drug reactions (ADRs) were retrieved from VigiBase. Macrolides and fluoroquinolones were compared with amoxicillin by using the reporting odds ratio (ROR) as a measure of disproportionality. Macrolides were then compared with fluoroquinolones. Results Overall, 6810 reports of ADRs were retrieved: 62% of them were serious and 35% concerned female. Macrolides were more frequently associated with "atrial fibrillation" (ROR = 1.26, CI 1.02-1.57) and "ventricular fibrillation" ROR = 2.60, CI 1.92-3.54) than fluoroquinolones. Antimicrobials more frequently reported for "cardiac disorder" were azithromycin (375 reports) and clarithromycin (302) for macrolides and levofloxacin (470) and moxifloxacin (391) for fluoroquinolones. Conclusion Our data highlighted that macrolides and fluoroquinolones may influence cardiac rhythm and suggest caution in the prescribing of these drugs to patients with hidden cardiovascular risk factors. Although these ADRs seem to be not common, they have a notable impact in clinical practice because of the huge number of the exposed subjects.

Aims Human papilloma virus (HPV) is the cause of different types of carcinoma. Despite the remarkable effectiveness of the HPV vaccines, there have been many complaints about their risk-benefit profile due to adverse events following immunization (AEFI). The purpose of this study is to analyse the safety profile of the HPV vaccine basing on real-life data derived from reports of suspected AEFIs collected in the US Vaccine Adverse Events Reporting System (VAERS) and assess if the searches on Google overlap with spontaneous reporting. Methods We collected all the reports in VAERS between January 2007 to December 2017 related to the HPV vaccines. A disproportionality analysis using reporting odds ratio (ROR) with 95% confidence interval was performed. Results Over the 10-year period, 55 356 reports of AEFI related to HPV vaccines were retrieved in VAERS, corresponding to 224 863 vaccine-event pairs. The highest number of reports was related to Gardasil (n = 42 244). The two events more frequently reported and statistically significant for HPV vaccines were dizziness (n = 6259; ROR = 2.60; 95% confidence interval 2.53-2.66) and syncope (n = 6004; ROR = 6.28; 95% confidence interval 6.12-6.44). The trends of spontaneous reporting and Google searches overlap. Conclusion The AEFI analysis showed that the events most frequently reported were non-serious and listed in the corresponding summary of product characteristics. Potential safety signals arose regarding less frequent AEFIs that would deserve further investigation. It is extremely important to disseminate correct and evidence-based scientific information.

Aim Direct oral anticoagulants (DOACs) have shown noninferiority to warfarin for stroke prevention in nonvalvular atrial fibrillation (AF) and a more promising safety profile. Unanswered safety aspects remain to be addressed and available evidence on the risk associated with these drugs are conflicting. In order to contribute to the debate on their safety profile, we conducted a comparative analysis of the reports of suspected adverse drug reactions (ADRs) associated with DOACs in VigiBase. Methods Study based on reports of suspected ADRs held in VigiBase as at December 2014, in which a DOAC or warfarin were administered in patients with nonvalvular AF and listed as suspected/interacting drugs. Medical Dictionary for Regulatory Activities was used to classify ADRs. Reporting odds ratio (ROR) with 95% confidence interval were calculated. Results with P ≤ 0.05 were statistically significant. Results We retrieved 32 972 reports. We identified 204 ADRs with a ROR >1 (P ≤ 0.05) and we focused on 105 reactions. Positive ROR emerged for DOACs and gastrointestinal haemorrhage compared with warfarin [(1.6 (1.47–1.75)], but no disproportionality with cerebral haemorrhage was found [0.31 (0.28–0.34)]. We identified other potential signals that have not been associated with DOACs previously. Conclusions As well as premarketing authorization clinical trial studies, we found a reduced risk of intracranial haemorrhage, but an increased risk of gastrointestinal haemorrhage in patients treated with DOACs compared to warfarin. We provide new data and we highlight several differences between the three novel oral anticoagulants, in the rate and type of ADRs occurred