Roberto Bonaiuti

Drug-induced taste and smell alterations: a case/non-case evaluation of an Italian database of spontaneous adverse drug reaction reporting

AbstractBackground: The frequency and clinical features of drug-related taste and/or smell impairments are currently unclear. Objective: The aim of this study was to identify major drug classes associated with taste and smell alterations reported to the Italian spontaneous adverse drug reaction (ADR) reporting database. Methods: The association between drug and altered taste or smell was investigated by case/non-case methodology. The reporting odds ratio (ROR) was used as a measure of disproportionality. Cases were defined as patients with at least one ADR related to taste or smell impairments. The non-cases included all patients without any ADRs related to taste or smell alterations. Results: According to the selection criteria, 52 166 reports were included in the analysis. Overall, 182 cases of drug-related taste and/or smell dysfunctions were identified. Statistically significant unadjusted RORs were reported for macrolides (n = 31; 7.1; 95% CI 4.8, 10.5), terbinafine (the only drug reported within the group of antimycotics belonging to the Anatomical Therapeutic Chemical class D01AE) [n=17; 76.4; 95% CI 44.0, 132.6], fluoroquinolones (n= 15; 1.7; 95% CI 1.0, 2.8) and protein kinase inhibitors (n= 10; 4.0; 95% CI 2.1, 7.7). When RORs were adjusted for sex and age category, the disproportion remained statistically significant for all of the previously mentioned drug classes. Conclusions: Taste and/or smell abnormalities are common, sometimes unexpected and often persistent complaints of patients during pharmacological treatments. Physicians should be aware of the impact of these ADRs on patients’ quality of life.

Patients tracking and identifying inside hospital: A multilayer method to plan an RFId solution

This paper shows a method to get a patient tracking RFId solution, basing on a multilayer planning architecture. This approach is thought to guarantee that the found technical solution is as much as possible coherent to the very initial idea. Project aims, functional requirements and technical constraints are defined in order to arrive to an active RFId solution to track and identify patients inside a hospital. The article also deals with economical issues and physical design aspects. In this work its also defined a three phases process for patient tracking, that could serve as a guideline for different technical solutions to the same problem.

DC-ATLAS: a systems biology resource to dissect receptor specific signal transduction in dendritic cells

BackgroundThe advent of Systems Biology has been accompanied by the blooming of pathway databases. Currently pathways are defined generically with respect to the organ or cell type where a reaction takes place. The cell type specificity of the reactions is the foundation of immunological research, and capturing this specificity is of paramount importance when using pathway-based analyses to decipher complex immunological datasets. Here, we present DC-ATLAS, a novel and versatile resource for the interpretation of high-throughput data generated perturbing the signaling network of dendritic cells (DCs).ResultsPathways are annotated using a novel data model, the Biological Connection Markup Language (BCML), a SBGN-compliant data format developed to store the large amount of information collected. The application of DC-ATLAS to pathway-based analysis of the transcriptional program of DCs stimulated with agonists of the toll-like receptor family allows an integrated description of the flow of information from the cellular sensors to the functional outcome, capturing the temporal series of activation events by grouping sets of reactions that occur at different time points in well-defined functional modules.ConclusionsThe initiative significantly improves our understanding of DC biology and regulatory networks. Developing a systems biology approach for immune system holds the promise of translating knowledge on the immune system into more successful immunotherapy strategies.

Risk of acute and serious liver injury associated to nimesulide and other NSAIDs: data from drug‐induced liver injury case‐control study in Italy

Aim Drug‐induced liver injury is one of the most serious adverse drug reactions and the most frequent reason for restriction of indications or withdrawal of drugs. Some nonsteroidal anti‐inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity. We estimated the risk of acute and serious liver injury associated with the use of nimesulide and other NSAIDs, with a prevalence of use greater than or equal to 5%. Methods This is a multicentre case–control study carried out in nine Italian hospitals from October 2010 to January 2014. Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders not related to chronic conditions, not involving the liver. Adjusted odds ratio (ORs) with 95% confidence interval (CI) were calculated initially with a bivariate and then multivariate analysis. Results We included 179 cases matched to 1770 controls. Adjusted OR for acute serious liver injury associated with all NSAIDs was 1.69, 95% CI 1.21–2.37. Thirty cases were exposed to nimesulide (adjusted OR 2.10, 95% CI 1.28–3.47); the risk increased according to the length of exposure (OR > 30 days: 12.55, 95% CI 1.73–90.88) and to higher doses (OR 10.69, 95% CI 4.02–28.44). Risk of hepatotoxicity was increased also for ibuprofen, used both at recommended dosages (OR 1.92, 95% CI 1.13–3.26) and at higher doses (OR 3.73, 95% CI 1.11–12.46) and for ketoprofen ≥ 150 mg (OR 4.65, 95% CI 1.33–10.00). Conclusion Among all NSAIDs, nimesulide is associated with the higher risk, ibuprofen and high doses of ketoprofen are also associated with a modestly increased risk of hepatotoxicity.

Safety profile of antiviral medications: A pharmacovigilance study using the Italian spontaneous-reporting database

PURPOSE The results of an analysis of suspected antiviral-associated adverse drug reactions (ADRs) in Italy over a 22-year period are presented. METHODS A case/non-case analysis was conducted using ADR reports compiled in the nationwide spontaneous-reporting database through September 2010. All reported events included in the analysis were evaluated and coded by drug safety experts; causality assessments were performed according to the algorithm of Naranjo et al. The association between an adverse reaction and antiviral use was assessed by estimating the reporting odds ratio (ROR), with 95% confidence interval (CI), as a measure of disproportionality. RESULTS Overall, 863 reports of suspected ADRs involving antivirals and 42,430 reports of adverse reactions to other drugs were identified; of those events, 3.3% and 64.3% were determined to be definite or probable ADRs, respectively, and an additional 32.4% were deemed possibly drug related. Several ADRs were disproportionately associated with antivirals relative to other drugs: renal colic (ROR, 25.5; 95% CI, 13.3-49.0), lactic acidosis (ROR, 18.6; 95% CI, 9.2-37.7), depression (ROR, 18.0; 95% CI, 11.6-27.9), anemia (ROR, 15.9; 95% CI, 12.3-20.4), hallucination (ROR, 4.3; 95% CI, 2.7-7.1), neutropenia (ROR, 4.1; 95% CI, 2.9-5.8), acute renal failure (ROR, 3.9; 95% CI, 2.3-6.4), fever (ROR, 3.8; 95% CI, 2.8-5.1), hyperpyrexia (ROR, 2.9; 95% CI, 1.7-4.9), and asthenia (ROR, 1.8; 95% CI, 1.2-2.8). CONCLUSION Analysis of data from a large Italian database showed that, among antiviral agents, the ribavirin-interferon combination, acyclovir, valacyclovir, indinavir, and zidovudine accounted for the most serious hematologic, neuropsychiatric, and renal ADRs.

Evaluation of bivalent human papillomavirus (HPV) vaccine safety and tolerability in a sample of 25 year old Tuscan women

The aim of this study was to gather data on the safety of the HPV-16/18 AS04-adjuvated vaccine among women aged 25, evaluating the frequency and severity of adverse events reported after vaccination and to compare the results obtained with previously published data regarding a sample of Italian preadolescents. Every woman residing in the province of Florence and in the age group targeted by the cervical cancer screening was invited to participate. Participants registered daily, for 14 d post-vaccination, solicited local and systemic reactions, as well as unsolicited adverse events in a developed ad hoc safety diary card. Data were collected in a database in Access and analyzed using STATA 11 SE statistical software. A total of 271 participants were recruited in the study group. All three diary cards were completed and delivered by 186 subjects (85.7% of participants). In all, a total of 616 diary cards were collected: 216 after the 1st dose, 209 after the 2nd dose and 191 after the 3rd dose. No severe symptoms were registered. The most frequently reported adverse reaction proved to be pain at the site of injection (83.4% of doses), followed by local swelling (20.8%) and pyrexia (14.6%). The safety and tolerability of the HPV-16/18 AS04-adjuvated vaccine in this sample of adult women aged 25 did not differ much from that previously observed in a sample of preadolescents Italian girls. Fever and local pain were however more frequently registered in our sample of adult women.

Stillbirth and perinatal care: are professionals trained to address parents’ needs?

OBJECTIVE To assess current practices of health care providers (HCPs) caring for women experiencing a stillbirth and to explore their needs for training to better support bereaved families. DESIGN Nationwide cross-sectional survey. The main outcome measures were the evaluation of HCPs cognition, emotions and behaviours with regard to the care of women with a stillbirth care, as well as their compliance with international guidelines. PARTICIPANTS 750 HCPs, in 11 Italian hospitals, were administered a multiple-choice questionnaire. FINDINGS The response rate was 89.9%; the majority (94.1%) were female, with a mean age of 37.6 (SD = 10.4) years. Midwives were the most represented (72.8%). Half of the respondents recommended immediate birth; only 55% routinely bathed and dressed stillborn babies for their parents to see, while 44.4% of HCPs immediately took the babies away without allowing parents to properly say goodbye to them. More than half felt inadequate and some even reported having failed to provide support to the family when caring for a woman with stillbirth in the past. The need for professional training courses was expressed by 90.2%, and three-quarters had never previously attended a course on perinatal bereavement care. When answers by Italian HCPs are systematically evaluated with reference to international guidelines, the results were very poor with only 27.9% of respondents reported having created memories of the baby and less than 3% complied with all recommendations in the areas of respect for baby and parents, appropriate birth options, and aftercare. KEY CONCLUSIONS There is a substantial gap between the standards of care defined by international guidelines and the practices currently in place in Italy. Italian HCPs feel an urgent need to be offered professional training courses to better meet the needs of grieving families. IMPLICATION FOR PRACTICE Perinatal HCPs should be aware of their pivotal role in helping bereaved parents after stillbirth and perinatal loss, and seek appropriate training.

The use of complementary and alternative medicines during breastfeeding: results from the Herbal supplements in Breastfeeding InvesTigation (HaBIT) study

The use of complementary and alternative medicines (CAMs) during breastfeeding is increasing, mainly because of their presumed greater safety compared with conventional medications. However, CAMs can cause serious adverse effects, and there is limited high‐quality evidence supporting their use during lactation. In Italy, specific investigations on the attitude of lactating women towards CAMs are lacking. The Herbal supplements in Breastfeeding InvesTigation (HaBIT) study aimed to explore attitudes to and knowledge on CAMs among lactating women.

A systematic review of the risk factors for clinical response to opioids for all-age patients with cancer-related pain and presentation of the paediatric STOP pain study

BackgroundInter-patient variability in response to opioids is well known but a comprehensive definition of its pathophysiological mechanism is still lacking and, more importantly, no studies have focused on children. The STOP Pain project aimed to evaluate the risk factors that contribute to clinical response and adverse drug reactions to opioids by means of a systematic review and a clinical investigation on paediatric oncological patients.MethodsWe conducted a systematic literature search in EMBASE and PubMed up to the 24th of November 2016 following Cochrane Handbook and PRISMA guidelines. Two independent reviewers screened titles and abstracts along with full-text papers; disagreements were resolved by discussion with two other independent reviewers. We used a data extraction form to provide details of the included studies, and conducted quality assessment using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.ResultsYoung age, lung or gastrointestinal cancer, neuropathic or breakthrough pain and anxiety or sleep disturbance were associated to a worse response to opioid analgesia. No clear association was identified in literature regarding gender, ethnicity, weight, presence of metastases, biochemical or hematological factors. Studies in children were lacking. Between June 2011 and April 2014, the Italian STOP Pain project enrolled 87 paediatric cancer patients under treatment with opioids (morphine, codeine, oxycodone, fentanyl and tramadol).ConclusionsFuture studies on cancer pain should be designed with consideration for the highlighted factors to enhance our understanding of opioid non-response and safety. Studies in children are mandatory.Trial registrationCRD42017057740.

Liver Injury due to Amoxicillin vs. Amoxicillin/Clavulanate: A Subgroup Analysis of a Drug-Induced Liver Injury Case-Control Study in Italy

Objective: Several studies showed that amoxicillin plus clavulanic acid (co-amoxiclav) is one of the most common agents associated to serious Drug Induced Liver Injury (DILI). We estimated the risk of acute serious DILI associated with amoxicillin alone compared with co-amoxiclav, through a multicenter case-control study carried out in nine Italian hospitals from October 2010 to January 2014. Methods: Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders, not related to chronic conditions and not involving the liver. Adjusted Odds Ratio (ORs) with 95% CI were calculated initially with a bivariate and then multivariate analysis. Results: We analysed 179 cases matched to 1770 controls. Seven cases were exposed to amoxicillin (adjusted OR 1.69, 95% CI 0.72-3.98) and 22 cases to co-amoxiclav (adjusted OR 3.00, 95% CI 1.76-5.40). Conclusions: Co-amoxiclav almost doubled the risk of serious acute liver injury compared to amoxicillin alone. The incidence of co-amoxiclav induced DILI is very low but the widespread use of this drug by the general population makes the risk clinically relevant. The often inappropriate prescription of antimicrobial agents, and in particular of co-amoxiclav, could expose a given patient to a life-threatening risk compared to a negligible clinical benefit.