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Intravitreal anti-vascular endothelial growth factor (VEGF) drugs aflibercept and ranibizumab are used in neovascular retinal diseases but may be associated with non-ocular haemorrhage. Our objective was to compare the risk of non-ocular haemorrhage with intravitreal aflibercept versus intravitreal ranibizumab and with individual intravitreal anti-VEGFs versus intravitreal dexamethasone. A retrospective cohort study was conducted using four Italian claims databases, covering 18 million inhabitants from 2011 to 2016. Incident aflibercept users were matched 1:4 to incident ranibizumab users. The outcome was incident non-ocular haemorrhage requiring hospitalisation. Incidence per 1000 person-years (PYs) was estimated. Patients were followed for 180 days using an intention-to-treat (ITT) approach. An as-treated (AT) approach was also employed, using grace periods of 60 or 90 days. Analyses were repeated for aflibercept versus dexamethasone and ranibizumab versus dexamethasone. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. We identified incident users of intravitreal ranibizumab (n = 21,766), aflibercept (n = 3150) and dexamethasone (n = 3900). The incidence of haemorrhage was four events per 1000 PYs for each drug. Aflibercept was not associated with increased risk versus ranibizumab at 180 days (HR 0.97 [95% CI 0.37–2.56]). Results were consistent in the AT analysis (HR 1.19 [95% CI 0.52–2.75]). No increased risk was found for aflibercept and ranibizumab at 180 days versus dexamethasone (HR 0.70 [95% CI 0.30–2.60] and HR 0.67 [95% CI 0.33–1.38], respectively). No association was identified between intravitreal aflibercept and non-ocular haemorrhage versus ranibizumab. A comparable risk for these intravitreal anti-VEGFs and intravitreal dexamethasone was observed.

Introduction: Since vascular endothelial growth factor (VEGF) regulates several aspects of the central nervous system, particularly in dopaminergic neurons, VEGF inhibitors may be linked to Parkinson-like events and dementia, or variants of these diseases. Two recent case reports have found a potential link between intravitreal anti-VEGF use and Parkinson’s disease (PD) and dementia.\ud \ud Aim: To evaluate disproportionality in a large spontaneous reporting database concerning intravitreal anti-VEGF drugs and PD or dementia, and related conditions.\ud \ud Methods: Using VigiBase, individual case safety reports (ICSRs) attributed to intravitreal ranibizumab, aflibercept, pegaptanib, and bevacizumab were identified from 2010 to 2016. Within Standardised Narrow Medical Dictionary for Regulatory Activities (MedDRA®) Queries (SMQs) for “Parkinson-like events” and “Dementia,” suspected events were identified using preferred terms (PTs). The Proportional Reporting Ratio (PRR) was estimated with the lower 95% confidence intervals (CIs) for all drug-event pairs with ≥3 suspected events. The vigiGrade completeness score was reported for the ICSRs. The analyses were repeated, including only persons aged 65 and over.\ud \ud Results: Out of 18.9 million ICSRs, 7,945 (0.004%) concerned intravitreal anti-VEGF drugs. Of these, 27 (0.34%) were identified concerning the SMQs “Dementia” (N = 17, 62.96%) and “Parkinson-like events” (N = 10, 37.94%) in persons of all ages. Among persons age 65 and over, 4,758 (59.88% of relevant ICSRs) ICSRs were identified for anti-VEGF drugs. When restricting disproportionality analysis to persons aged 65 and over, no disproportionality was seen for any of the drug-event pairs at the level of SMQ. However, on analysing disproportionality by PT, a potential signal emerged for intravitreal ranibizumab and Parkinson’s disease [N = 6 ICSRs; PRR: 3.05 (95% CI: 1.36-6.81)]. In general, the vigiGrade completeness score was low for all the ICSRs of interest, as no ICSR had a score >0.8.\ud \ud Conclusion: Present findings suggest a potential signal for Parkinson’s disease related to intravitreal ranibizumab. This is supported by several biologically plausible mechanisms but requires confirmation through pharmacoepidemiological studies, especially because of the low number of cases.

Objective The aim of this retrospective population-based cohort study is to in-depth investigate gender-specific drug utilization pattern in pediatric outpatient population. Methods By using a large administrative database of the Local Health Unit of Caserta (Southern Italy), a pediatric cohort from the birth to 18 years has been observed over six years (from 1st January 2010 to 31st December 2015). Yearly prevalence of drug use per 100 inhabitants as well as the median number of prescriptions was stratifying by gender. Prevalence of acute and recurrent use of the most frequently used active substances has been calculated for the year 2015. Results A decreasing trend of prevalence of drug use (by 3.2%, with a reduction of median prescription number) was observed in children for both sexes, from 2010 to 2015. In 2015, the drug classes most commonly used among children of any age were modestly but consistently prescribed more to males than to females: systemic anti-infective drugs (M=43.5%; F=42.3%), respiratory tract drugs (M=29.0%; F=26.1%), and hormones (M=13.1%; F=11.3%). Irrespective to the gender, beclomethasone was the most utilized active substance in the first two years of life, while thereafter amoxicillin/clavulanate in combination. Conclusions In a large scale of pediatric outpatients no major difference was seen between genders, although commonly used drug classes, in particular, antibiotics, respiratory tract drugs and hormones are prescribed modestly but consistently more to males than to females. Our utilization data can support research exercises on specific medicine that could have a large impact on pediatric population.

Aim: Primary endpoint was to report polypharmacy distribution in the general population vs ≥65 years old people and to examine the frequency of drug–drug interactions (DDIs) in the Health Local Unit of Palermo, Italy, in relationship with patients’ age. Methods: Drug prescription data for the year 2014 were extracted from the database of the Local Health Unit of Palermo Province, Italy. Patients were divided into five age groups (0–13, 14–64, 65–69, 70–74, and ≥75 year old). The detection of potential DDIs in polypharmacy profiles was performed with NavFarma software (Infologic srl, Padova, Italia), with DDI classification provided by tool Micromedex Drug Reax (Truven Health Analitics, Michigan, USA). Results: We analyzed data of 1,324,641 patients, and 15,801,191 medical prescription were recorded; of these, 11,337,796 regarded chronic conditions. The drug prescriptions reached the highest values in the 65–69 and 70–74 age groups (p = 0.005 and p = 0.008 vs age 14–64 respectively). An overall amount of 6,094,373 DDIs were detected, of which 47,173 were contraindicated. Median number of DDIs was higher in 65–69 and 70–74 age groups (p = 0.008 and p = 0.012 vs age 14–64, respectively). Regarding contraindicated DDIs a significant difference was detected comparing 14–64 vs ≥65 age groups (p = 0.010 vs 65–69 group, p= 0.005 vs 70–74 group and ≥75 group). Conclusions: Polypharmacy is a phenomenon acquiring increasing dimensions also in our province. It interests particularly the older subjects, and assumes a dramatic accent when it is put in relationship with the frequency of DDIs. A proactive vigilance about potential life threatening drug interactions is mandatory.