Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance.

INTRODUCTION: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≥6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. METHODS: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009-2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). RESULTS: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H)RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power (p=0.42). CONCLUSIONS: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations

Test of CPT Symmetry and Quantum Mechanics with Experimental data from CPLEAR

We use fits to recent published CPLEAR data on neutral kaon decays to $\pi^+\pi^-$ and $\pi e\nu$ to constrain the CPT--violation parameters appearing in a formulation of the neutral kaon system as an open quantum-mechanical system. The obtained upper limits of the CPT--violation parameters are approaching the range suggested by certain ideas concerning quantum gravity.Comment: 9 pages of uuencoded postscript (includes 3 figures

Tests of the Equivalence Principle with Neutral Kaons

We test the Principle of Equivalence for particles and antiparticles, using CPLEAR data on tagged K0 and K0bar decays into pi^+ pi^-. For the first time, we search for possible annual, monthly and diurnal modulations of the observables |eta_{+-}| and phi_{+-}, that could be correlated with variations in astrophysical potentials. Within the accuracy of CPLEAR, the measured values of |eta_{+-}| and phi_{+-} are found not to be correlated with changes of the gravitational potential. We analyze data assuming effective scalar, vector and tensor interactions, and we conclude that the Principle of Equivalence between particles and antiparticles holds to a level of 6.5, 4.3 and 1.8 x 10^{-9}, respectively, for scalar, vector and tensor potentials originating from the Sun with a range much greater than the distance Earth-Sun. We also study energy-dependent effects that might arise from vector or tensor interactions. Finally, we compile upper limits on the gravitational coupling difference between K0 and K0bar as a function of the scalar, vector and tensor interaction range.Comment: 15 pages latex 2e, five figures, one style file (cernart.csl) incorporate

Contribution of CPLEAR to the physics of the neutral kaon system

We present the physics results of the CP-- and CPT--violation measurements performed by CPLEAR. CPLEAR has experimentally determined for the first time, the violation of T invariance and is able to disentangle all the CP-- and CPT--violating quantities from each other. This allows each of the CPT violating parameters to be determined with a precision of a few $10^{-4}$ and, in particular, the mass and width equality between the \kn and \knb to be tested down to the level of $10^{-19}$ GeV. Moreover, the precision of the CPLEAR measurements allows us to probe for the first time physics on a scale approaching the Planck mass

Experimental tests of CPT symmetry and quantum mechanics at CPLEAR

We review a phenomenological parametrization of an open quantum-mechanical formalism for CPT violation in the neutral kaon system, and constrain the parameters using fits to recent CPLEAR data.We review a phenomenological parametrization of an open quantum-mechanical formalism for CPT violation in the neutral kaon system, and constrain the parameters using fits to recent CPLEAR data

Dispersion relation analysis of the neutral kaon regeneration amplitude in carbon

We apply a forward dispersion relation to the regeneration amplitude for kaon scattering on \PCtw using all available data. The CPLEAR data at low energies allow the determination of the net contribution from the subthreshold region which turns out to be much smaller than earlier evaluations, solving a long standing puzzle

Determination of the T- and CPT-violation parameters in the neutral-kaon system using the Bell-Steinberger relation and data from CPLEAR

Data from the CPLEAR experiment, together with the most recent world averages for some of the neutral-kaon parameters, were constrained with the Bell--Steinberger (or unitarity) relation, allowing the T-violation parameter \ree and the CPT-violation parameter \imd of the neutral-kaon mixing matrix to be determined with an increased accuracy: \ree = (164.9 \pm 2.5)\times 10^{-5}, \imd = ( 2.4 \pm 5.0)\times 10^{-5}. Moreover, the constraint allows the CPT-violation parameter for the neutral-kaon semileptonic decays, \rey, to be determined for the first time. The $\Delta S \neq \Delta Q$ parameters \rexm and \imxp are given with an increased accuracy. The quantity $\mathrm{Re}(y~+~x_-)$, which enters the T-violation CPLEAR asymmetry previously published, is determined to be $(0.2 \pm 0.3)\times 10^{-3}$. The value obtained for \red is in agreement with the one resulting from a previous unconstrained fit and has a slightly smaller error

Experimental tests of CPT symmetry and quantum mechanics at CPLEAR

We review a phenomenological parametrization of an open quantum-mechanical formalism for CPT violation in the neutral kaon system, and constrain the parameters using fits to recent CPLEAR data

Measurement of the KL−KSK_{L}-K_{S} mass difference using semileptonic decays of tagged neutral kaons

We report on a new measurement of the \kl--\ks\ mass difference \dm\ using the CPLEAR full data sample of neutral-kaon decays to \semi. The result is \dm = (0.5295 \pm 0.0020_{\stat} \pm 0.0003_{\syst}) \times 10^{10}\ \hbs. It includes earlier data reported in Ref. \cite{deltam1}. A measurement of the \dsdq\ violating parameter \rex\ is also obtained