Carlo Giaquinto

University-Hospital of Padova, Padua, Veneto, Italy

Are you Carlo Giaquinto?

Claim your profile

Publications (217)1312.39 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Recent estimates indicate an increase in the prevalence of skin diseases in children. Few large epidemiologic studies have examined prevalence trends in Europe. This study evaluated the incidence and prevalence of frequently occurring pediatric skin diseases (PSDs) in Italy as seen by family pediatricians (FPs). Data were retrospectively extracted from the Pedianet database (2006-2012) in children ages 0 to 14 years presenting with a skin disease at their FP. The incidence and prevalence estimates were calculated per year and stratified according to sex, age, and geographic area. A mean of 145,233 children (52.1% male) across five Italian regions were registered with their participating FP for a total of 913,253 person-years of follow-up. The majority of patients were from the northeast (44.6%) and 37.7% were ages 5-9 years. Incidence estimates (new cases/1,000 person-years) for most PSDs increased from 2006 to 2012, the highest being for atopic dermatitis (AD) (14.1 vs 16.5), acute urticaria (10.1 vs 11.6), and contact dermatitis (9.3 vs 10.8), whereas psoriasis remained unchanged over the 7 years (0.61 vs 0.57). In contrast, prevalence estimates (cases/100 patients) increased two to three times for several PSDs, including AD (2.7% vs 8.5%), seborrheic dermatitis (0.5% vs 1.6%), chronic urticaria (0.4% vs 0.8%), and psoriasis (0.09% vs 0.22%). Differences in prevalence according to age range and geographic area were observed for psoriasis, AD, and urticaria. This study provides comprehensive evidence of the increasing prevalence and incidence of PSDs across Italy. Additional causality studies to address this important clinical and psychosocial problem are recommended. © 2015 Wiley Periodicals, Inc.
    Pediatric Dermatology 04/2015; DOI:10.1111/pde.12568 · 1.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The first evidence-based recommendations for rotavirus vaccination in Europe were prepared at the time of licensure of two live oral rotavirus vaccines (Rotarix™, GlaxoSmithKline, and RotaTeq®, Sanofipasteur-MSD) in 2006 and published in 2008. Since then several countries in Europe and more globally have adopted universal rotavirus vaccination of all healthy infants as part of their national immunization programs (NIP). The experience from these NIPs has produced a wealth of post-introduction effectiveness data that, together with the evidence from pre-licensure efficacy trials presented in the 2008 Recommendations, support the case of rotavirus vaccination in Europe.The prelicensure safety trials of Rotarix™ and RotaTeq®, each in populations of more than 60.000 infants, did not reveal risk of intussusception (IS), but post-vaccination surveillance in several countries, particularly Australia and Mexico, has established that the risk of IS for both vaccines after the first dose might be between 1:50.000 and 1:80.000. While it may be argued that the risk is acceptable vis-àis the great benefits of rotavirus vaccination, this argument alone may not suffice, and every effort should be made to reduce the risk of IS. Considerable evidence, including post-vaccination surveillance data from Germany, suggests that the risk of IS can be reduced by early administration of the first dose of oral rotavirus vaccine. The previous ESPID/ESPGHAN recommendations held that the first dose of oral rotavirus vaccine should be given between 6 and 12 weeks of age; this recommendation is sustained but with an emphasis towards the lower range of the recommended age, i.e. preferably between 6 to 8 weeks of age. At the time of the earlier recommendations experience of rotavirus vaccination in premature infants and other special target groups was limited. It is now recommended with greater confidence than before that prematurely born infants should be vaccinated according to their calendar age as recommended for full term infants. It is now strongly recommended that all HIV-infected or HIV-exposed infants be vaccinated with oral rotavirus vaccine. While specific information on many immunodeficiencies is lacking, infants with known severe combined immunodeficiency should not receive live rotavirus vaccine.
    The Pediatric Infectious Disease Journal 04/2015; DOI:10.1097/INF.0000000000000683 · 3.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained. © 2015 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.
  • [Show abstract] [Hide abstract]
    ABSTRACT: To describe the pharmacokinetics of darunavir in pregnant HIV-infected women in the third trimester and post-partum.
    Journal of Antimicrobial Chemotherapy 10/2014; DOI:10.1093/jac/dku400 · 5.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. Conclusion: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.
    European Journal of Pediatrics 09/2014; 174(4). DOI:10.1007/s00431-014-2398-z · 1.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Twice-daily darunavir/ritonavir is indicated in treatment-experienced children (>= 3 years). This study assessed once-daily administration in treatment-naive adolescents. Methods: Phase 2, 48-week, open-label, single-arm study evaluating pharmacokinetics, safety and efficacy of once-daily darunavir/ritonavir 800/100 mg in treatment-naive, HIV-1-infected adolescents (>= 12 to < 18 years, >= 40 kg) with zidovudine/lamivudine or abacavir/lamivudine. Results: Twelve patients (67% female; median 14.4 years) were enrolled. After 24 and 48 weeks, respectively, 11 of 12 (92%) and 10 of 12 (83%) patients achieved viral load <50 copies/mL (intent-to-treat time-to-loss of virologic response); all had >= 1 log(10) drop in viral load versus baseline. Median CD4(+) cell count increased by 175 and 221 cells/mm(3) (intent-to-treat-noncompleter -failure) after 24 and 48 weeks, respectively. Eighty-three percent of patients were adherent to darunavir/ritonavir. One patient was never suppressed and 1 patient rebounded. No patients developed darunavir resistance-associated mutations or lost phenotypic susceptibility to any commercially available protease inhibitor or any background nucleoside reverse transcriptase inhibitor. Eleven patients (92%) reported >= 1 adverse event (AE), considered in 2 patients to be at least possibly related to darunavir (gastrointestinal-related events and dizziness). Four patients had >= 1 serious AE. Three patients reported >= 1 grade 3/4 AE; no serious or grade 3/4 AEs were considered darunavir related. No patients discontinued because of AEs. Conclusions: Over 48 weeks, once-daily darunavir/ritonavir 800/100 mg plus NRTIs was effective and well-tolerated for treatment of HIV-1-infected, antiretroviral-naive adolescents (>= 12 to <18 years). These findings support use of once-daily darunavir/ritonavir 800/100 mg in this population.
    The Pediatric Infectious Disease Journal 09/2014; 33(9):940-5. DOI:10.1097/INF.0000000000000308 · 3.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied the effect of pregnancy on atazanavir pharmacokinetics in presence and absence of tenofovir.
    Antiviral therapy 07/2014; DOI:10.3851/IMP2820 · 3.14 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Children deserve medicines that are adapted to their needs. The need to include children in drug development has been recognised increasingly over the past few decades. Legal and regulatory frameworks are well established in the EU and US. The amount of work done to study medicines for children is significantly greater than it was 10years go. Proof-of-concept has been demonstrated for all segments of the paediatric drug development pipeline. It is now time to examine how the practice of developing medicines for children has evolved within those frameworks and to determine how that work should be generalised. This review describes the development of medicines for children and critically appraises the work that has been done within those frameworks. Significant effort is needed to realize the potential provided by the current regulatory framework. Using the work programme of the Global Research in Paediatrics (GRiP) Network of Excellence as a template we outline current work and future growing points.
    Advanced drug delivery reviews 06/2014; 73. DOI:10.1016/j.addr.2014.02.003 · 12.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background In the Highly Active Antiretroviral Therapy (HAART) era, the prognosis of children perinatally infected with HIV-1 has significantly improved, so the number of perinatally-infected females entering child-bearing age and experiencing motherhood is increasing. Methods A description of the medical history and pregnancy outcomes of women with perinatal acquired HIV-1 infection enrolled in the Italian Register for HIV infection in Children. Results Twenty-three women had 29 pregnancies. They had started an antiretroviral therapy at a median of 7.7 years (interquartile range, IQR 2.3 - 11.4), and had experienced a median of 4 therapeutic regimens (IQR 2–6). Twenty women (87%) had taken zidovudine (AZT) before pregnancy, in 14 cases as a starting monotherapy. In 21 pregnancies a protease inhibitor-based regimen was used. At delivery, the median of CD4+ T lymphocytes was 450/μL (IQR 275–522), and no viral load was detectable in 15 cases (reported in 21 pregnancies). Twenty-eight children were delivered through caesarean section (median gestational age: 38 weeks, IQR 36–38, median birth weight: 2550 grams, IQR 2270 – 3000). Intravenous AZT was administered during delivery in 26 cases. All children received oral AZT (median: 42 days, IQR 31 – 42), with no adverse events reported. No child acquired HIV-1 infection. Conclusions Despite a long history of maternal infection, multiple antiretroviral regimens and, perhaps, the development of drug-resistant viruses, the risk of mother-to-child transmission does not seem to have increased among the second-generation of HIV-1 exposed infants.
    BMC Infectious Diseases 05/2014; 14(1):277. DOI:10.1186/1471-2334-14-277 · 2.56 Impact Factor
  • Vaccine 05/2014; 32(34). DOI:10.1016/j.vaccine.2014.05.029 · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)–infected children of low-middleincome countries (LMIC). Methods. An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models. Results. Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26–33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5–22.9). Having tuberculosis co-infection orWHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4–17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudineefavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution. Conclusions. Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.
    05/2014; 4(1). DOI:10.1093/jpids/piu032
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rotavirus gastroenteritis is a vaccine-preventable disease that confers a high medical and economic burden in more developed countries and can be fatal in less developed countries. Two vaccines with high efficacy and good safety profiles were approved and made available in Europe in 2006. We present an overview of the status of rotavirus vaccination in Europe. We discuss the drivers (including high effectiveness and effect of universal rotavirus vaccination) and barriers (including low awareness of disease burden, perception of unfavourable cost-effectiveness, and potential safety concerns) to the implementation of universal rotavirus vaccination in Europe. By February, 2014, national universal rotavirus vaccination had been implemented in Belgium, Luxembourg, Austria, Finland, Greece, Luxembourg, Norway, and the UK. Four other German states have issued recommendations and reimbursement is provided by sickness funds. Other countries were at various stages of recommending or implementing universal rotavirus vaccination.
    The Lancet Infectious Diseases 05/2014; 14(5):416-425. DOI:10.1016/S1473-3099(14)70035-0 · 19.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Atazanavir and lopinavir represent the main HIV protease inhibitors recommended in pregnancy, but comparative data in pregnant women are limited. METHODS: Women from a national observational study, exposed in pregnancy to either atazanavir or lopinavir, were compared for glucose and lipid profiles, liver function tests, CD4 count, HIV RNA and main pregnancy outcomes. Statistical methods included univariate and multivariable analyses. RESULTS: The study population included 428 pregnancies (lopinavir, 322; atazanavir, 106). The lopinavir group was characterized by higher rates of HIV diagnosis in pregnancy and treatment indication for maternal health, lower CD4 counts, higher HIV RNA levels, less frequent antiretroviral treatment at conception and shorter duration of drug exposure during pregnancy. No differences in pregnancy outcomes, glucose metabolism and weight gain were observed. The two groups also showed in a multivariable analysis similar odds for detectable HIV RNA in the third trimester (adjusted OR 0.85, 95% CI 0.35-2.10, P = 0.730). Total lipid levels were significantly higher in the lopinavir group (median values in the third trimester 239 versus 221 mg/dL for total cholesterol and 226 versus 181 mg/dL for triglycerides; P < 0.001 for both comparisons) and bilirubin levels were significantly higher in the atazanavir group (1.53 versus 0.46 mg/dL, P < 0.001). CONCLUSIONS: In this observational study atazanavir and lopinavir showed similar safety and activity in pregnancy, with no differences in the main pregnancy outcomes. Atazanavir use was associated with a better lipid profile and with higher bilirubin levels. Overall, the study findings confirm that these two HIV protease inhibitors represent equally valid alternative options. KEYWORDS: HIV RNA, bilirubin, cholesterol, pre-term delivery, triglycerides
    Journal of Antimicrobial Chemotherapy 05/2014; 69(5):1377-84. DOI:10.1093/jac/dkt497 · 5.44 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Correlations between clinical/immunological treatment failure and viral load (VL) detected by dried blood spot (DBS) sampling were explored in HIV-1-infected children of Uganda. Of 104 children on cART, 12.5% had clinical and/or immunological failure, while 28.8%, 44.2% and 26.9% had VL <1000, 1000-5000, and >5000 cp/ml, respectively. Clinical/immunological failure poorly predicted virological failure.
    Journal of clinical microbiology 04/2014; 52(7). DOI:10.1128/JCM.00961-14 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe factors determining retention and survival among HIV-infected children and adolescents engaged in two health care delivery models in Kampala, Uganda: one is a community home-based care (CHBC) and the other is a facility-based family-centred approach (FBFCA). This retrospective cohort study reviewed records from children aged from 0 to 18 years engaged in the two models from 2003 to 2010 focussing on retention/loss to follow-up, mortality, use of antiretroviral therapy (ART), and clinical characteristics. Kaplan Meier survival curves with log rank tests were used to describe and compare retention and survival. Overall, 1,623 children were included, 90.0% (1460/1623) from the CHBC. Children completed an average of 4.2 years of follow-up (maximum 7.7 years). Median age was 53 (IQR: 11-109) months at enrolment. In the CHBC, retention differed significantly between patients on ART and those not (log-rank test, adjusted, P < 0.001). Comparing ART patients in both models, there was no significant difference in long-term survival (log-rank test, P = 0.308, adjusted, P = 0.489), while retention was higher in the CHBC: 94.8% versus 84.7% in the FBFCA (log-rank test, P < 0.001, adjusted P = 0.006). Irrespective of model of care, children receiving ART had better retention in care and survival.
    04/2014; 2014:852489. DOI:10.1155/2014/852489
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Fosamprenavir, combined with low-dose ritonavir (FPV/r), is indicated for treatment of HIV-infected children aged ≥ 6 years in Europe. Our purpose was to assess the safety of licensed use of FPV/r in HIV-infected children reported to six cohorts in the European Pregnancy and Paediatric HIV Cohort Collaboration. Retrospective analysis of individual patient data for all children aged 6-18 years taking the licensed dose of FPV up to 31/12/10. Adverse events (clinical events and absolute neutrophil counts, total cholesterol and triglycerides, and alanine transaminase) were summarised and DAIDS gradings characterised severity. Ninety-two HIV-infected children aged 6-18 years took the licensed dose, comprising 3% of the total number of children in follow-up in participating cohorts. Median age at antiretroviral therapy initiation was 6 years (interquartile range 1-11 years), and median age at start of FPV/r was 15 years (12-17 years). Estimated median time on an FPV-containing regimen was 52 months, with a total of 266.9 patient years of exposure overall. Half (54%) were on an FPV-containing regimen at last follow-up. Rates of grade 3/4 events were generally low for all biochemical toxicity markers, and no serious adverse events considered to be causally related to FPV/r were reported. Results suggest that long-term licensed dose FPV-containing regimens appear to be generally well tolerated with few reported toxicities in HIV-infected children in Europe, although relatively infrequently prescribed. No serious events were reported
    Pharmacoepidemiology and Drug Safety 03/2014; 23(3):321-5. DOI:10.1002/pds.3543 · 3.17 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Epstein-Barr Virus (EBV) is involved in a wide range of malignancies, particularly in immunocompromised subjects. In Africa, EBV primary infection occurs during early childhood, but little is known about EBV load in HIV-1-infected children.Methods. Dried Blood Spot samples from 213 HIV-1-infected children, 140 on antiretroviral therapy (ART), were collected at the Nsambya Hospital in Kampala, Uganda. Nucleic acids were extracted and analysed for quantification of EBV types 1 and 2, 16S ribosomal DNA (16S rDNA), a marker of microbial translocation, and HIV-1 RNA.Results. Ninety-two of 140(66%) children on ART and 57 of 73(78%) ART-naive children had detectable EBV-DNA levels. Co-infection with both EBV types was less frequent in ART-treated than in ART-naive children (OR=0.54[95%CI 0.30-0.98];P= .042). EBV-DNA levels were lower in the former (3.99±0.59 vs 4.22±0.54 log10 copies/ml;P= .006) and tended to be inversely associated with time on ART. EBV-DNA levels were higher in children with HIV-1 RNA>3 log10 copies/ml of blood (regression coefficient=0.32[95%CI 0.05-0.59];P= .020) and correlated with circulating 16S rDNA levels(rs=0.25[95%CI 0.02-0.46];P= .031).Conclusions. These findings suggest that ART, by limiting HIV-1 replication, microbial translocation and related immune activation, prevents super-infection with both EBV types and keeps EBV viremia down, thus potentially reducing the risk of EBV-associated lymphomas.
    The Journal of Infectious Diseases 02/2014; 210(3). DOI:10.1093/infdis/jiu099 · 5.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Late onset neonatal sepsis (LOS) has a high mortality and the optimal management is poorly defined. We aimed to evaluate new expert panel-derived criteria to define LOS and characterize the current management and antibiotic susceptibility of LOS-causing organisms in Europe. A prospective observational study enrolled infants aged 4 to 90 days in five European countries. Clinical and laboratory findings as well as empiric treatment were recorded and patients were followed until the end of antibiotic therapy. Failure was defined as a change of primary antibiotic, no resolution of clinical signs, appearance of new signs/pathogens or death. Antibiotic therapy was considered appropriate if the organism was susceptible to at least one empiric antibiotic. 113 infants (median age 14 days, 62 % ≤1500 g) were recruited; 61 % were culture proven cases (28 CoNS, 24 Enterobacteriaceae, 11 other Gram-positives and 6 Gram-negative non-fermentative organisms). The predictive value of the expert-panel criteria to identify patients with a culture proven LOS was 61 % (95 % CI 52 % to 70 %). Around one third of Enterobacteriaceae were resistant to ampicillin + or cefotaxime + gentamicin but only 10 % to meropenem. Empiric treatment contained a total of 43 different antibiotic regimens. All-cause mortality was 8 % with an additional 45 % classified as failure of empiric therapy, mainly due to change of primary antibiotics (42/60). Conclusions: The expert panel-derived diagnostic criteria performed well identifying a high rate of culture proven sepsis. Current management of LOS in Europe is extremely variable suggesting an urgent need of evidence-based guidelines.
    European Journal of Pediatrics 02/2014; 173(8). DOI:10.1007/s00431-014-2279-5 · 1.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Highly Active Antiretroviral Therapy (HAART) changed the natural history of pediatric HIV infection. This review focuses on trends of HIV-associated cancers in childhood in the HAART era and analyses potential pathogenetic mechanisms. HAART reduced AIDS-defined malignancies (ADM), but incidence of several non-ADM is increasing. HIV-associated immune activation and inflammation, promoting tumorigenesis, can only partially be reduced by HAART. In addition, HIV-infected children may undergo accelerated immune senescence that favors cancer development. How HAART affects this condition is an open question. Lastly, there is no evidence that prenatal exposure to HAART increases the risk of cancer in childhood, but long-term studies are needed.
    Cancer letters 02/2014; DOI:10.1016/j.canlet.2014.02.002 · 5.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Data mining in spontaneous reporting databases has shown that drug-induced liver injury is infrequently reported in children. Our objectives were to (i) identify drugs potentially associated with acute liver injury (ALI) in children and adolescents using electronic healthcare record (EHR) data; and (ii) to evaluate the significance and novelty of these associations. We identified potential cases of ALI during exposure to any prescribed/dispensed drug for individuals <18 years old from the EU-ADR network, which includes seven databases from three countries, covering the years 1996-2010. Several new methods for signal detection were applied to identify all statistically significant associations between drugs and ALI. A drug was considered statistically significantly associated with ALI, using all other time as a reference category, if the 95 % CI lower band of the relative risk was >1 and in the presence of at least three exposed cases of ALI. Potentially new signals were distinguished from already known associations concerning ALI (whether in adults and/or in the paediatric population) through manual review of published literature and drug product labels. The study population comprised 4,838,146 individuals aged <18 years, who contributed an overall 25,575,132 person-years of follow-up. Within this population, we identified 1,015 potential cases of ALI. Overall, 20 positive drug-ALI associations were detected. The associations between ALI and domperidone, flunisolide and human insulin were considered as potentially new signals. Citalopram and cetirizine have been previously described as hepatotoxic in adults but not in children, while all remaining associations were already known in both adults and children. Data mining of multiple EHR databases for signal detection confirmed known associations between ALI and several drugs, and identified some potentially new signals in children that require further investigation through formal epidemiologic studies. This study shows that EHRs may complement traditional spontaneous reporting systems for signal detection and strengthening.
    Drug Safety 02/2014; 37(2):99-108. DOI:10.1007/s40264-013-0132-9 · 2.62 Impact Factor

Publication Stats

3k Citations
1,312.39 Total Impact Points

Institutions

  • 2006–2014
    • University-Hospital of Padova
      Padua, Veneto, Italy
    • Medical Research Council (UK)
      • MRC Clinical Trials Unit
      London, ENG, United Kingdom
    • Emory University
      • Department of Global Health
      Atlanta, GA, United States
  • 1988–2014
    • University of Padova
      • Department of Pediatrics
      Padua, Veneto, Italy
  • 2013
    • Second University of Naples
      Caserta, Campania, Italy
  • 2011
    • Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico
      • Neonatology and Neonatal Intensive Care
      Milano, Lombardy, Italy
  • 2008
    • Public Health England
      • Centre for Infections Services
      Londinium, England, United Kingdom
    • University of Tampere
      Tammerfors, Province of Western Finland, Finland
  • 2006–2007
    • University of Florence
      Florens, Tuscany, Italy
  • 2004
    • Instituto de Salud Carlos III
      Madrid, Madrid, Spain
  • 2001–2003
    • Erasmus Universiteit Rotterdam
      Rotterdam, South Holland, Netherlands
    • University College London
      • Institute of Child Health
      London, ENG, United Kingdom
  • 2000
    • St George's, University of London
      Londinium, England, United Kingdom
  • 1987–1996
    • It-Robotics
      Vicenza, Veneto, Italy
  • 1995
    • University of London
      Londinium, England, United Kingdom
  • 1992
    • Interuniversity Research Centre on Bioactive Peptides
      Napoli, Campania, Italy