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Ersilia Lucenteforte,1 Niccolò Lombardi,1,* Davide Liborio Vetrano,2,* Domenico La Carpia,2,* Zuzana Mitrova,3 Ursula Kirchmayer,3 Giovanni Corrao,4 Francesco Lapi,5 Alessandro Mugelli,1 Alfredo Vannacci1 On behalf of the Italian Group for Appropriate Drug prescription in the Elderly (I-GrADE) 1Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Florence, Italy; 2Department of Geriatrics Catholic University, Rome, Italy; 3Department of Epidemiology, ASL 1 Rome, Italy; 4Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy; 5Epidemiology Unit, ARS Toscana, Florence, Italy *These authors contributed equally to this work Abstract: Avoiding medications in which the risks outweigh the benefits in the elderly patient is a challenge for physicians, and different criteria to identify inappropriate prescription (IP) exist to aid prescribers. Definition of IP indicators in the Italian geriatric population affected by cardiovascular disease and chronic comorbidities could be extremely useful for prescribers and could offer advantages from a public health perspective. The purpose of the present study was to identify IP indicators by means of a systematic literature review coupled with consensus criteria. A systematic search of PubMed, EMBASE, and CENTRAL databases was conducted, with the search structured around four themes and combining each with the Boolean operator “and”. The first regarded “prescriptions”, the second “adverse events”, the third “cardiovascular conditions”, and the last was planned to identify studies on “older people”. Two investigators independently reviewed titles, abstracts, full texts, and selected articles addressing IP in the elderly affected by cardiovascular condition using the following inclusion criteria: studies on people aged ≥65 years; studies on patients with no restriction on age but with data on subjects aged ≥65 years; and observational effectiveness studies. The database searches produced 5,742 citations. After removing duplicates, titles and abstracts of 3,880 records were reviewed, and 374 full texts were retrieved that met inclusion criteria. Thus, 49 studies reporting 32 potential IP indicators were included in the study. IP indicators regarded mainly drug–drug interactions, cardio- and cerebrovascular risk, bleeding risk, and gastrointestinal risk; among them, only 19 included at least one study that showed significant results, triggering a potential warning for a specific drug or class of drugs in a specific context. This systematic review demonstrates that both cardiovascular and non-cardiovascular drugs increase the risk of adverse drug reactions in older adults with cardiovascular diseases. Keywords: inappropriate prescriptions, elderly, cardiovascular diseases, chronic diseases, systematic review

Guidelines Towards a Pain-Free Hospital, published in 2001 in Italy, determined an increasing spread of No-Pain Hospital Committees across the country and supported a more effective pain control in hospital. However, few hospitals adopted such protocols. To date, a thorough investigation on quality of pain management documentation is lacking. The present survey aimed to evaluate the quality of pain management documentation reported in medical and hospital discharge records. The study reviewed records of 2,459 patients discharged every Wednesday of November 2006 in 29 Tuscany hospitals. Among 2,459 patients, 51.5 % were males. Patients were aged between 0 and 90 years or above and were mostly (24.93 %) between 70 and 79 years; most of them (47.1 %) were hospitalized in Medicine ward. At hospital admission, less than half of examined records (40.3 %) reported pain-related items, and only 8.1 % reported how it was treated. During hospitalization, 39.6 % of the records reported the use of scales for measuring pain intensity and 49.7 % reported the pharmacological therapy. The present study highlights the lack of an exhaustive documentation of pain recording and management in the hospital setting. Therefore, healthcare providers should pay close attention to this relevant issue, and the quality of such documentation should be constantly monitored. [ABSTRACT FROM AUTHOR]

Summary What is known and Objective: Methotrexate (MTX) is widely used in the management of paediatric cancer with a generally favourable benefit/risk profile. We report an unusual adverse drug reaction with the first course of high-dose MTX in a paediatric patient and review the literature for similar cases. Case summary: An 11-year-old boy with small-cell osteoblastic osteosarcoma in the lower limb experienced a case of life-threatening anaphylaxis during the first course of high-dose MTX. The adverse event occurred during the first course, likely due to an immune-mediated mechanism. We postulate that prior antineoplastic treatment might have contributed to the immune response to MTX. What is new and Conclusion: Given that this reaction has rarely been reported, we discuss the present case with a review of other similar cases. Further studies are needed to substantiate this 'signal alarm' for serious MTX-related hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

Background: 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. [ABSTRACT FROM AUTHOR]

Background: Fluoroquinolones are widely used both in primary care and in hospital settings. Since the last comparison performed in Italy on the safety profiles of different fluoroquinolones, a new molecule, prulifloxacin, has been introduced into the market and several warnings concerning this class of drugs have been released. The aim of this study was to reassess the safety profiles of fluoroquinolones using the database of the Italian Interregional Group of Pharmacovigilance (IGP) and the administrative data of fluoroquinolone prescriptions.Methods: All adverse drug reactions (ADRs) reported in four Italian regions (Lombardy, Veneto, Emilia Romagna and Tuscany) were retrieved from the IGP database. Consumption data (defined daily dose [DDD]/1000 inhabitants/day) were used as denominators. Both single reports and all ADRs (classified by System Organ Classes and MedDRA Preferred Term [PT]) due to fluoroquinolones were considered as numerators of each analysis, comparing two periods (2005 vs 2006). All fluoroquinolones with at least ten reports per year were included in the analysis.Results: On the basis of 272 reports (532 single ADRs or PTs), patients did not show any statistically significant differences between 2005 and 2006 in terms of sex, age and number of concurrent medications. After adjustment for drug consumption, moxifloxacin showed the highest reporting rate (84.6 reports/DDD/1000 inhabitants/day; 15.4 serious reports/DDD/1000 inhabitants/day) followed by prulifloxacin (72.2; 22.2 serious) and levofloxacin (55.3; 30.6 serious) in 2005. An increment of ADR/report rates was observed over the 2 years for all fluoroquinolones except prulifloxacin, which had the lowest ADR reporting rate in 2006 (25.0; 12.5 serious). In 2006, the rate of serious ADRs associated with prulifloxacin was lower than with ciprofloxacin, while in 2005 serious events were almost equal for both compounds (55.6 vs 47.6 serious ADRs/DDD/1000 inhabitants/day). Ciprofloxacin showed the highest proportion of cutaneous PTs (e.g. rash, exanthema). Tendinopathies were mainly due to levofloxacin.Conclusions: These data suggest that different fluoroquinolones are characterized by different rates and types of ADRs. Among them, prulifloxacin was associated with more ADRs than other fluoroquinolones in 2005 but with fewer ADRs in 2006, when its consumption increased. Although these findings may represent an encouraging perspective towards a more appropriate use of fluoroquinolones because of their individual safety profiles, further pharmacoepidemiological studies must be performed to substantiate these results. [ABSTRACT FROM AUTHOR]

BACKGROUND: Because of co-morbidity, older persons are often exposed to use of an excessive number of drugs, which per se implies also use of inappropriate drugs or of potentially interacting drugs ('suboptimal prescribing'). Time trends of suboptimal prescribing in older, community dwellers have been poorly investigated, particularly in Italy. OBJECTIVE: To evaluate the time-course modification of suboptimal prescribing in older, community dwellers. METHODS: We conducted a study on an Italian cohort of older (aged>or=65 years), community dwellers for whom data were collected in a two-wave (1995 and 1999), population-based survey. Suboptimal prescribing was defined as occurrence of polypharmacy (>or=5 medications), prescription of inappropriate medications (according to 1991 Beers' criteria) and prescription of potentially interacting drugs (as identified by the Micromedex Drug-Reax system). All outcome variables were modelled as continuous and dichotomous. RESULTS: In 568 participants (59.9% women, mean+/-standard error age 72.7+/-0.2 years), polypharmacy and potentially interacting drugs were more prevalent in 1999 than in 1995, while prevalence of inappropriate drugs was lower in 1999. The proportion of participants receiving polypharmacy was nearly 3-fold greater in 1999 than in 1995 (21.6% vs 8.8%; p<0.001). After adjustment for disability, coronary artery disease/stroke, heart failure and other co-morbidities, polypharmacy was twice as prevalent in 1999 as in 1995, with a mean increase of 0.5 drugs per participant. In contrast, in models adjusted for the same variables and also for polypharmacy, inappropriate prescribing was reduced (60% lower prevalence, 0.06 mean reduction in prescriptions per participant) in 1999 compared with 1995. In multivariable models, no change was observed in the number of potentially interacting prescriptions. CONCLUSIONS: Between 1995 and 1999, the number of prescriptions received by a cohort of older, community dwellers increased substantially, even after controlling for co-morbidity. On the other hand, when controlling for polypharmacy, other indicators of suboptimal prescribing remained unaffected or even decreased, suggesting that even increasing levels of polypharmacy do not necessarily imply other forms of suboptimal prescribing among older persons. [ABSTRACT FROM AUTHOR]

Background: The inhibitors of HMG-CoA reductase ('statins') are widely prescribed hypolipidaemic drugs, which have been evaluated in several clinical trials involving hundreds of thousands of patients. From a safety perspective, both clinical trials and post-marketing surveillance have demonstrated that statins are generally well tolerated, with rare serious adverse drug reactions (ADRs) that affect mainly muscle, liver and kidney. However, recent interest has been focused on a potential risk of psychiatric ADRs associated with statins, including memory loss, depression, suicidality, aggression and antisocial behaviour. Special attention is currently being paid to the potential for statin-induced sleep disorders.Objective: To investigate the hypothesis that statins may be associated with psychiatric adverse events using quantitative and qualitative signal analysis.Methods: The Interregional Group of Pharmacovigilance database holds reports of suspected ADRs submitted since 1988 from eight Italian regions. In the present analysis, only reports ranked at least 'possible', according to WHO causality assessment criteria, were considered. Association between statins and psychiatric events was assessed by the case/non-case methodology, calculating the ADR reporting odds ratio (ROR) as a measure of disproportionality. Cases were defined as patients with at least one reported ADR combined with the system organ class (SOC) 'psychiatric disorders'. The non-cases comprised all patients who did not experience an ADR related to the SOC 'psychiatric disorders'. Index reports comprised all ADR reports involving at least one statin, while all ADR reports not involving statins as suspected drugs were used as controls.Results: According to selection criteria, 35,314 reports were included in the analysis. A total of 71 psychiatric preferred terms combined with statins were identified in 60 reports. Among them, 14 reports (23.3%) noted a positive rechallenge. Both the unadjusted (0.8; 95% CI 0.6, 1.1) and adjusted ROR (0.7; 95% CI 0.6, 1.0) suggested a lower rate of reports of psychiatric events for statins as a whole class compared with all other drugs, although the difference was not significant. The five most frequently reported psychiatric events combined with statins were insomnia, somnolence, agitation, confusion and hallucination. Only insomnia was reported with higher frequency for statins compared with all other drugs (ROR = 3.3; 95% CI 1.9, 5.7), while confusion was reported with a lower frequency (ROR = 0.4; 95% CI 0.1, 0.9). Amongst statins available in Italy, only simvastatin (ROR = 0.5; 95% CI 0.2, 0.9) showed a significantly lower rate of reports of psychiatric events compared with all other drugs together.Conclusion: A relatively small number of possible statin-associated psychiatric ADRs have been found in our database. No significant risks for a higher overall reporting of psychiatric ADRs associated with statins were identified in comparison with all other drugs combined. However, statin-associated insomnia resulted in a significant ROR that requires further investigation. [ABSTRACT FROM AUTHOR]

The original version of this article, published on 26 November 2019 contained a mistake. [ABSTRACT FROM AUTHOR]

Chronic Migraine (CM) is a relevant public health concern. This study therefore aims to assess the epidemiology of CM in primary care in Italy by testing five operational algorithms defining CM. A set of algorithms defining CM were developed to estimate the prevalence and incidence rate of CM in a cohort of patients active in Health Search Database (HSD) on January 1, 2016. [Extracted from the article]