A ranked list of 23 adverse drug events judged as important in pharmacovigilance was created to permit focused data mining. The list will need to be updated periodically as knowledge on drug safety evolves and new issues in drug safety arise.

Objectives: To analyse an Italian database of spontaneous reporting of suspected adverse drug reactions in order to compare the safety profile of amoxicillin and amoxicillin/clavulanic acid.Methods: Data were retrieved from the spontaneous reports collected by six Italian regions (the GIF database) from January 1988 to June 2005. Drug utilization data were also available for the two drugs. The comparison between amoxicillin and amoxicillin/clavulanic acid was made using the x 2 or Student's t-test, when appropriate. Disproportionality in reporting of adverse events was assessed using reporting odds ratio methodology.Results: Up to June 2005, the GIF database collected 37 906 reports, of which 1088 were related to amoxicillin/clavulanic acid and 1095 to amoxicillin. The percentage of skin reactions was statistically higher for amoxicillin (82%) than for amoxicillin/clavulanic acid (76%); on the contrary, the percentage of gastrointestinal, hepatic and haematological reactions was significantly higher for amoxicillin/ clavulanic acid (13%, 4% and 2%, respectively) than for amoxicillin (7%, 1% and 1%, respectively). Amoxicillin/clavulanic acid seems to be associated with a higher risk of Stevens-Johnson syndrome, purpura and hepatitis than amoxicillin alone. In particular, the reporting rate of hepatitis is on average 9-fold higher for amoxicillin/clavulanic acid than for amoxicillin.Conclusions: Analysis shows a different safety profile for the two selected drugs. The combination of amoxicillin/clavulanic acid has been increasingly used in Italy and now represents the most frequently antibiotic prescribed by Italian general practitioners. Given the documented level of inappropriate use of b-lactams in Italy, these results should be taken into account by physicians before prescribing amoxicillin/clavulanic acid to patients.

BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.