Central nervous system-active drug abused and overdose in children: a worldwide exploratory study using the WHO pharmacovigilance database.

Recent epidemiological studies have reported an increase in central nervous system (CNS)-active drug abuse rates in paediatric settings, raising several public health concerns. No study to date has explored this issue worldwide. We performed an extensive analysis of drugs abuse/overdose reported for children in the last decade by using the largest pharmacovigilance database, i.e. the VigiBase, collecting adverse drug reaction reports that involved at least one suspect drug belonging to the Anatomical Therapeutic Chemical code "Nervous System" through the Standardised Medical Dictionary for Drug Regulatory Affairs Queries for Drug abuse. 8.682 reports matched our criteria. An increase in reporting activity was observed, starting from 2014; an intentional overdose was reported more frequently than an accidental one, with a difference between age groups. We retrieved 997 reports with death outcome. These referred more to adolescents (n = 538) than subjects of any other paediatric age group. Paracetamol and opioid analgesics were the most common suspect drugs in deaths across all age groups due to hypoxic-ischaemic encephalopathy, brain death, and cardio-respiratory arrest.Conclusion: The number of reports associated with drug abuse and overdose is increasing (for opioid and paracetamol-containing products) and a considerable number of adverse drug reactions are serious. Data on the patterns of use of such medicines from each country may help in implementing strategies of risk-minimisation and renewing healthcare recommendations worldwide. An increased clinical awareness of drug abuse and overdose is warranted, while continuing to provide effective treatments. What is Known: • The large increase in paediatric prescriptions for CNS-active drugs in the last 20 years has recently raised public health concerns about drug abuse and overdose. • No study to date has examined this issue in paediatric patients worldwide. What is New: • The number of paediatric reports associated with CNS drug abuse and intentional overdose is increasing, including those with fatal outcome; over 4 years; more than 35% of the reports was entered from European countries. • Opioid and paracetamol were most frequently suspected for ADRs with fatal outcome across all age groups, due to hypoxic-ischaemic encephalopathy and cardio-respiratory arrest, suggesting the need to implement strategies of risk-minimisation.

Sex-related differences in prevalence, treatment and outcomes in patients with atrial fibrillation.

To analyze sex-related differences about AF prevalence, use of OAC and outcomes focusing on the older age classes. We used administrative data of the Lombardy Region, describing period prevalence, use of OAC and outcomes from 2002 to 2014 for all patients diagnosed with AF. AF prevalence over the 2002-2014 period was higher in males than in females (2.7% vs. 2.1%, p < 0.001), increasing with age. From 2003 to 2014, not treated AF patients decreased mostly in males (from 40.3 to 33.7% with respect to 43.7-39.8% in females). Age-stratified adjusted logistic regression analysis found that females were more likely treated with OAC when < 65 years in 2003 (OR 1.51, 95% CI 1.35-1.69) and in 2014 (OR 1.32, 95% CI 1.13-1.53); contrariwise, were less likely treated with OAC when age ≥ 75 years, in 2003 (OR 0.92, 95% CI 0.86-0.98) and in 2014 (OR 0.77, 95% CI 0.72-0.81).Adjusted Cox regression analysis confirmed that female AF patients had a higher risk of stroke (HR 1.18, 95% CI 1.14-1.21) and a lower risk of major bleeding (HR 0.83, 95% CI 0.80-0.86), while, had a lower risk for all-cause death (HR 0.82, 95% CI 0.80-0.83). AF prevalence was higher in male than in female patients, while thromboembolic risk was higher in female. Older female patients were under-treated with OAC particularly in recent years. Over long-term follow-up, female had a higher risk of stroke and a lower risk of major bleeding and all-cause death.

Diabetic macular edema, innovative technologies and economic impact: New opportunities for the Lombardy Region healthcare system?

PURPOSE: Diabetic macular edema (DME) is a leading cause of vision loss and blindness. The aim of this study was to evaluate the economic benefits of introducing additional alternative technologies (Dexamethasone intravitreal implant - DEX - and Aflibercept injections), compared with the historical scenario of Ranibizumab intravitreal injections. METHODS: A 3-year budget impact model was developed, taking into consideration the perspective of the Lombardy Region Healthcare Service (LRHS). Total administration costs (real-life data retrieved from clinical practice at three Departments of Ophthalmology) as well as costs related to the management of potential adverse events (information collected from the literature) were analysed. RESULTS: Over a 36-month horizon, the results showed that a higher consumption of DEX could lead to significant economic savings for the Regional Healthcare Service, ranging from a minimum of -4.35% (if DEX were used only in the second-line of treatment) to a maximum of -12.97% (if DEX were used in both the first-line and second-line), including the potential impact of adverse events. Therapy costs with Aflibercept and Ranibizumab were similar. CONCLUSIONS: This study demonstrates that concentrating all eligible patients within the Ranibizumab regimen is unlikely to represent a cost-effective strategy. Indeed, significant economic advantages would be achieved by introducing the other licensed alternatives, Dexamethasone implant and Aflibercept, thus optimising DME Italian healthcare expenditure. The results demonstrate DEX as an advantageous technological alternative for the target population affected by DME, both as a first- and second-line treatment option, reducing the economic burden of the pathology for the Regional/National Health Service.

Burden of Moderate-to-Severe Plaque Psoriasis and New Therapeutic Approaches (Secukinumab): An Italian Perspective.

UNLABELLED: Psoriasis is a chronic immune-mediated inflammatory skin disease commonly categorized as mild, moderate, or severe. Moderate-to-severe psoriasis is associated with significant comorbidity and has been shown to severely impair quality of life. Moreover, psoriasis is associated with high costs, including those associated with treatment, which have increased recently with the inclusion of biological systemic agents (most recently secukinumab) as available treatment options. However, despite clear evidence of their value in the treatment of moderate-to-severe plaque psoriasis, in Italy access to the biological agents remains limited to dermatological centers originally involved in the Psocare network. The impact of secukinumab entry into the market in Italy is still to be determined, but we believe that it will be associated with significant changes in the way in which biological treatments for psoriasis are accessed and prescribed in Italy. It is noteworthy that in January 2015, the European Medicines Agency approved secukinumab as first-line systemic therapy in this indication. FUNDING: Novartis, Italy.

[Resistance of Pseudomonas aeruginosa to ciprofloxacin and levofloxacin: 1998-2002]. / Resistenza di Pseudomonas aeruginosa a ciprofloxacina e levofloxacina: 1998-2002.

The aim of this study was to evaluate resistance rates to ciprofloxacin and levofloxacin of Pseudomonas aeruginosa (n=1917 strains) isolated at Laboratory of Microbiology at L. Sacco Teaching Hospital in Milan, Italy in the period between January 1998 and October 2002. Twenty-five percent of tested strains were isolated from sputum, 18% from bronchial lavage, 10% from urine, 9% from ear, 4.5% from blood and 26% from other materials. Ciprofloxacin-resistant strains were 121/ 411 (29%) in 1998, 158/ 526 (30%) in 1999, 136/ 400 (34%) in 2000, 129/ 390 (33%) in 2001 and 53/ 190 (28%) in 2002. Resistance rates for levofloxacin were 132/472 (28%) in 1999, 104/ 400 (26%) in 2000, 101/ 390 (26 %) in 2001 and 47/ 190 (25%) in 2002. Our data highlight overall stability in resistance to ciprofloxacin and levofloxacin with minor variations for ciprofloxacin. Moreover, in contrast with international worldwide studies, resistance rates to ciprofloxacin remained higher than those related to levofloxacin throughout the period studied.

Impact of therapeutic drug monitoring of antiretroviral drugs in routine clinical management of patients infected with human immunodeficiency virus and related health care costs: a real-life study in a large cohort of patients.

BACKGROUND: Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness. METHODS: A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other. RESULTS: The cohort consisted of 5,347 patients (3,861 males and 1,486 females) of mean age 43.9±12.5 years. We found that TDM had been used in 143 of these patients, among whom adherence with therapy was significantly higher than among those in whom TDM had not been used (94% versus 78%). In TDM-controlled patients, the mean length of HIV-related hospitalization stay and mean cost of hospitalization were significantly reduced with respect to those observed in the group in which TDM had not been used (7.21 days versus 29.47 days and €293 versus €688, respectively). CONCLUSION: Inclusion of TDM as part of routine clinical optimization of drug dosing in HIV-infected patients is associated with higher adherence to therapy, reduced length of hospitalization stay, and reduced cost of illness.

Economic evaluation of initial antiretroviral therapy for HIV-infected patients: an update of Italian guidelines.

INTRODUCTION: Highly active antiretroviral therapy (HAART) has allowed many HIV-infected patients to enjoy longer survival and a better quality of life. We performed an economic analysis to estimate the cost-effectiveness of HAART regimens in Italy for managing HIV-naïve infected patients with a viral load below 100,000 copies/mL. PATIENTS AND METHODS: The population considered in the model consisted of adult subjects with an HIV viral load below 100,000 copies/mL who received antiretroviral HAART treatment for the first time, according to the Italian National Guidelines with recommendation grade A1. The incremental cost-effectiveness analysis of quality-adjusted life years (QALYs) was carried out by means of a Markov model. Both the outcomes (QALYs) and the costs were discounted by 3.5%. The time horizon adopted in the model was 10 years. The point of view of the analysis was that of the Italian national health service. RESULTS: The tenofovir (TDF)/emtricitabine (FTC)/rilpivirine (RPV) single-tablet regimen (STR) (€7,417.00) revealed the lowest mean treatment cost. TDF/FTC + raltegravir (RAL) showed a better quality of life (0.906 QALY/year), followed by TDF/FTC/RPV (STR; 0.900 QALY/year), TDF/FTC + RPV (multipill regimen) (0.889 QALY/year), and TDF/FTC + atazanavir (ATV/r) (0.886 QALY/year). TDF/FTC/RPV (STR) appeared to be the most cost-effective therapeutic choice (€13,655.00), followed by TDF/FTC + RPV (multipill regimen) (€15,803.00), and TDF/FTC + efavirenz (EFV) (€16,181.00). The sensitivity analysis on the main variables confirmed the validity of the base case scenario. CONCLUSION: STR (TDF/FTC/RPV) is the most cost-effective treatment strategy compared with the other therapeutic regimens recommended by the Italian guidelines for the treatment of naïve patients with a viral load <100,000 copies/mL. The inclusion of adverse-event management of HIV-infected patients affects the cost-effectiveness ratio of all HAART regimens.