We performed a systematic review and meta-analysis of the empirical evidence on the association of metabolic syndrome and its components with colorectal cancer incidence and mortality. A systematic literature search of multiple electronic databases was conducted and complemented by cross-referencing to identify studies published before 31 October 2012. Every included study was to report risk estimates with 95 % confidence intervals for the association between metabolic syndrome and colorectal cancer (incidence or mortality). Core items of identified studies were independently extracted by two reviewers, and results were summarized by standard methods of meta-analysis. We identified 17 studies, which reported on 49 data sets with 11,462 cancer cases. Metabolic syndrome was associated with an increased risk of colorectal cancer incidence and mortality in both men (RR: 1.33, 95 % CI 1.18-1.50, and 1.36, 1.25-1.48, respectively) and women (RR: 1.41, 1.18-1.70, and 1.16, 1.03-1.30, respectively). The risk estimates changed little depending on type of study (cohort vs non cohort), populations (US, Europe, Asia), cancer site (colon and rectum), or definition of the syndrome. The risk estimates for any single factor of the syndrome were significant for higher values of BMI/waist (RR: 1.19, 95 % CI 1.10-1.28), dysglycemia (RR: 1.29, 1.11-1.49), and higher blood pressure (RR: 1.09, 1.01-1.18). Dysglycemia and/or higher BMI/waist explained most of the risk associated with metabolic syndrome. Metabolic syndrome is associated with an increased risk of colorectal cancer incidence and mortality in both sexes. The risk conveyed by the full syndrome is not superior to the sum of its parts.

MS is associated with a moderately increased risk of PBC. No single component explains the risk conveyed by the full syndrome.

AimDrug‐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 Some nonsteroidal anti‐inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity.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%.MethodsThis 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.ResultsWe 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).ConclusionAmong 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.

Enormous progress has been made globally in the use of evidence derived from patients' clinical information as they access their routine medical care. The value of real-world data lies in their complementary nature compared with data from randomised controlled trials: less detailed information on drug efficacy but longer observational periods and larger, more heterogeneous study populations reflecting clinical practice because individuals are included who would not usually be recruited in trials. Real-world data can be collected in various types of electronic sources, such as electronic health records, claims databases and drug or disease registries. These data sources vary in nature from country to country, according to national healthcare system structures and national policies. In Italy, a growing number of healthcare databases have been used to evaluate post-marketing drug utilisation and safety in the last two decades. The aim of this narrative review is to describe the available Italian sources of real-world data and their contribution to generating post-marketing evidence on drug use and safety. We also discuss the strengths and limitations of the most commonly used Italian healthcare databases in addressing various research questions concerning drug utilisation, comparative effectiveness and safety studies, as well as health technology assessment and other areas. Key PointsEnormous progress has been made in Italy and globally in the use of evidence derived from patients' clinical data as they access their routine medical care.Several data sources in Italy have been used to assess the effectiveness, safety and economic value of medications, including claims databases, electronic health records and patient registries.

AIMSThe aim of the study was to analyze the prescribing pattern of both newer and older AEDs. METHODSA population of almost 150 000 individuals registered with 123 general practitioners was included in this study. Patients who received at least one AED prescription over 2005-2011 were identified. The 1 year prevalence and cumulative incidence of AED use, by drug class and individual drug, were calculated over the study period. Potential predictors of starting therapy with newer AEDs were also investigated. RESULTSThe prevalence of use per 1000 inhabitants of older AEDs increased from 10.7 (95% CI10.1, 11.2) in 2005 to 13.0 (95% CI12.4, 13.6) in 2011, while the incidence remained stable. Newer AED incidence decreased from 9.4 (95% CI 8.9, 9.9) in 2005 to 7.0 (95% CI 6.6, 7.5) in 2011, with a peak of 15.5 (95% CI 14.8, 16.1) in 2006. Phenobarbital and valproic acid were the most commonly prescribed AEDs as starting therapy for epilepsy. Gabapentin and pregabalin accounted for most new pain-related prescriptions, while valproic acid and lamotrigine were increasingly used for mood disorders. Female gender (OR 1.36, 95% CI 1.20, 1.53), age ranging between 45-54 years (OR 1.39, 95% CI 1.16, 1.66) and pain as an indication (OR 16.7, 95% CI, 13.1,21.2) were associated with newer AEDs starting therapy. CONCLUSIONSOlder AEDs were mainly used for epileptic and mood disorders, while newer drugs were preferred for neuropathic pain. Gender, age, indication of use and year of starting therapy influenced the choice of AED type. The decrease of newer AED use during 2007 is probably related to the restricted reimbursement criteria for gabapentin and pregabalin.

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Dipeptidyl peptidase (DPP)-4 inhibitors are a class of oral drugs used for the treatment of type 2 diabetes mellitus (T2DM). The pharmacological inhibition of DPP-4 seems to also induce adverse events related to cytokine-induced inflammation. Recently, several clinical cases regarding the association of DPP-4 inhibitors and the onset of arthritis/arthralgia have been reported in the literature. Various mechanisms could be responsible for DPP-4 inhibitor-induced arthritis/arthralgia, and the increase of cytokines, chemokines, matrix metalloproteinases (MMPs) and genetic factors plays an important role. The US FDA published a safety announcement regarding the entire drug class, encouraging healthcare professionals and patients to pay attention to the occurrence of arthralgia during treatment with DPP-4 inhibitors; arthralgia could be assessed as a class adverse drug event for DPP-4 inhibitors. To summarize the evidence on the correlation between DPP-4 inhibitors and arthritis/arthralgia, and to explain the measures taken by the FDA with regard to arthralgia risk, we performed a literature review of recent evidence concerning this association. This review shows the necessity of other studies to better define the association between DPP-4 inhibitors and arthritis/arthralgia.

ObjectiveStevens-Johnson Syndrome (SJS) is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children.MethodsA multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child’s use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions.ResultsTwenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1st November 1999 and 31st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0–6.1). Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4–86.0). Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5–7.2), corticosteroids (adjusted OR 4.2; 95% CI 1.8–9.9) and paracetamol (adjusted OR 3.2; 95% CI 1.5–6.9). No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3–2.8).DiscussionOur study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.