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 Some nonsteroidal anti-inflammatory drugs (NSAIDs) were withdrawn from the market because of serious hepatotoxicity.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

Observation of the rare decay K_S -> pi^0mu^+mu^-

A search for the decay K_S -> pi^0mu^+mu^- has been made by the NA48/1 Collaboration at the CERN SPS accelerator. The data were collected during 2002 with a high-intensity K_S beam. Six events were found with a background expectation of 0.22^+0.18_-0.11 event. Using a vector matrix element and unit form factor, the measured branching ratio is B(K_S -> pi^0mu^+mu^-)=[2.9^+1.5_-1.2(stat)+/-0.2(syst)]x10^{-9}.Comment: 19 pages, 8 figures, 4 tables. To be published in Physics Letters

First Observation and Measurement of the Decay K+- -> pi+- e+ e- gamma

Using the full data set of the NA48/2 experiment, the decay K+- -> pi+- e+ e- gamma is observed for the first time, selecting 120 candidates with 7.3 +- 1.7 estimated background events. With K+- -> pi+- pi0D as normalisation channel, the branching ratio is determined in a model-independent way to be Br(K+- -> pi+- e+ e- gamma, m_eegamma > 260 MeV/c^2) = (1.19 +- 0.12_stat +- 0.04_syst) x 10^-8. This measured value and the spectrum of the e+ e- gamma invariant mass allow a comparison with predictions of Chiral Perturbation Theory.Comment: 13 pages, 3 figures. Accepted for publication in Phys.Lett.

First observation and branching fraction and decay parameter measurements of the weak radiative decay Xi0 --> Lambda e+e-

The weak radiative decay Xi0 --> Lambda e+e- has been detected for the first time. We find 412 candidates in the signal region, with an estimated background of 15 +/- 5 events. We determine the branching fraction B(Xi0 --> Lambda e+e-) = [7.6 +/- 0.4(stat) +/- 0.4(syst) +/- 0.2(norm)] x 10^{-6}, consistent with an internal bremsstrahlung process, and the decay asymmetry parameter alpha_{XiLambdaee} = -0.8 +/- 0.2, consistent with that of Xi0 --> Lambda gamma. The charge conjugate reaction Xi0_bar --> Lambda_bar e+e- has also been observed.Comment: 20 pages, 5 figures, 4 tables; revised: 19 pages, 4 figures, 4 tables, after reviewers' comments: 1 figure removed, 1 figure corrected, minor editorial changes; to be published in Phys. Lett.

Empirical parameterization of the K+- -> pi+- pi0 pi0 decay Dalitz plot

As first observed by the NA48/2 experiment at the CERN SPS, the \p0p0 invariant mass (M00) distribution from \kcnn decay shows a cusp-like anomaly at M00=2m+, where m+ is the charged pion mass. An analysis to extract the pi pi scattering lengths in the isospin I=0 and I=2 states, a0 and a2, respectively, has been recently reported. In the present work the Dalitz plot of this decay is fitted to a new empirical parameterization suitable for practical purposes, such as Monte Carlo simulations of K+- -> pi+- pi0 pi0 decays.Comment: 9 pages, 3 figures

Search for direct CP-violation in K+- --> pi+-pi0pi0 decays

A search for direct CP-violation in K+- --> pi+-pi0pi0 decays based on 47.14 million events has been performed by the NA48/2 experiment at the CERN SPS. The asymmetry in the Dalitz plot linear slopes A_g=(g^+ - g^-)/(g^+ + g^-) is measured to be A_g=(1.8 +- 2.6).10^{-4}. The design of the experiment and the method of analysis provide good control of instrumental charge asymmetries in this measurement. The precision of the result is limited by statistics and is almost one order of magnitude better than that of previous measurements by other experiments.Comment: 14 page

New Precise Measurements of the \xilamgam and \xisiggam Decay Asymmetries

The decay asymmetries of the weak radiative Hyperon decays Xi0 \to Lambda gamma and Xi0 \to Sigma0 gamma have been measured with high precision using data of the NA48/1 experiment at CERN. From about 52000 Xi0 \to Lambda gamma and 15000 Xi0 \to Sigma0 gamma decays, we obtain for the decay asymmetries alpha(Xi0 \to Lambda gamma) = -0.704 +/- 0.019(stat) +/- 0.064(syst) and alpha(Xi0 \to Sigma0 gamma) = -0.729 +/- 0.030(stat) +/- 0.076(syst), respectively. These results are in good agreement with previous experiments, but more precise.Comment: 14 pages, 4 figures, accepted for publication in PL

New measurement of the charged kaon semileptonic (Ke4) decay Branching Ratio and Hadronic Form Factors

A sample of more than one million Ke4 decay candidates with less than one percent background contamination has been collected by the NA48/2 experiment at the CERN SPS in 2003-2004, allowing a detailed study of the decay properties. The branching ratio, inclusive of radiative Ke4gamma decays, is measured to be BR(Ke4) = (4.257 +/- 0.016_exp +/- 0.031_ext) x 10-5 with a total relative error of 0.8%. This measurement complements the study of S- and P-wave hadronic form factors by assigning absolute values to the relative hadronic form factors obtained earlier in a simultaneous analysis of the pion-pion scattering lengths conducted on the same data sample. The overall form factor normalization f_s = 5.705 +/- 0.017_exp +/- 0.031_ext is obtained with a total relative precision of 0.6%.Comment: 21 pages, 5 figures, 5 tables, submitted to Phys. Lett.

Measurement of the Dalitz plot slope parameters of the K±→π±π+π−K^\pm\to\pi^\pm\pi^+\pi^- decay

The distribution of the $K^\pm\to\pi^\pm\pi^+\pi^-$ decays in the Dalitz plot has been measured by the NA48/2 experiment at the CERN SPS with a sample of $4.71\times 10^8$ fully reconstructed events. With the standard Particle Data Group parameterization the following values of the slope parameters were obtained: $g=(-21.134\pm0.017)\%$, $h=(1.848\pm0.040)\%$, $k=(-0.463\pm0.014)\%$. The quality and statistical accuracy of the data have allowed an improvement in precision by more than an order of magnitude, and are such as to warrant a more elaborate theoretical treatment, including pion-pion rescattering, which is in preparation.Comment: 14 pages, 5 figures. Version submitted to Phys. Lett. B. Slightly improved analysis and bibliography

First observation and study of the K± → π±π0e+e− decay

The NA48/2 experiment at CERN reports the first observation of the K±→π±π0e+e− decay from an exposure of 1.7×1011 charged kaon decays recorded in 2003-2004. A sample of 4919 candidates with 4.9% background contamination allows the determination of the branching ratio in the full kinematic region, BR(K±→π±π0e+e−)=(4.24±0.14)×10−6. The study of the kinematic space shows evidence for a structure dependent contribution in agreement with predictions based on chiral perturbation theory. Several P- and CP-violating asymmetries are also evaluated