Therapeutic drug monitoring to personalize dosing of imatinib, sunitinib, and pazopanib:A mixed methods study on barriers and facilitators

Background:Personalized dosing based on measurement of individual drug levels and adjusting the dose accordingly can improve efficacy and decrease unnecessary toxicity of oncological treatment. For imatinib, sunitinib, and pazopanib, this therapeutic drug monitoring (TDM)-guided dosing is, however, not routinely used, despite accumulating evidence favoring individualized dosing. Therefore, we aimed to identify and quantify (potential) barriers and facilitators in TDM-guided dosing for imatinib, sunitinib, and pazopanib. Methods: We performed a mixed methods study among all stakeholders involved: patients, healthcare professionals (HCPs), pharmaceutical companies, and health insurance companies. During the first qualitative part of this study, we performed semi-structured individual interviews and one focus group interview to identify all (potential) barriers and facilitators, and during the second quantitative part of this study, we used a web-based survey to quantify these findings. The interviews addressed the six domains of the implementation of change model of Grol and Wensing: (1) the innovation itself; (2) the HCP; (3) the patient; (4) social context; (5) organizational context; and (6) finances, law, and governance. Results: In the qualitative study, we interviewed 20 patients, 18 HCPs and 10 representatives of pharmaceutical and health insurance companies and identified 72 barriers and 90 facilitators. In the quantitative study, the survey was responded by 66 HCPs and 58 patients. Important barriers were on the domain of the HCP, such as a lack of experience with TDM (36.4%), on the domain of the patient, such as lack of awareness of TDM (39.7%), and the processing time for measurement and interpretation of the TDM result (40.9%) (organizational domain). Important facilitators were education of HCPs (95.5%), education of patients (87.9%) and facilitating an overview of when and where TDM measurements are being performed (86.4%). Conclusion: We identified and quantified important barriers and facilitators for the implementation of TDM-guided dosing for imatinib, sunitinib, and pazopanib. Based on our results, the implementation strategy should mainly focus on educating both HCPs and patients and on the organizational aspect of TDM.</p

Neutrino Quasielastic Scattering on Nuclear Targets: Parametrizing Transverse Enhancement (Meson Exchange Currents)

We present a parametrization of the observed enhancement in the transverse electron quasielastic (QE) response function for nucleons bound in carbon as a function of the square of the four momentum transfer ($Q^2$) in terms of a correction to the magnetic form factors of bound nucleons. The parametrization should also be applicable to the transverse cross section in neutrino scattering. If the transverse enhancement originates from meson exchange currents (MEC), then it is theoretically expected that any enhancement in the longitudinal or axial contributions is small. We present the predictions of the "Transverse Enhancement" model (which is based on electron scattering data only) for the $\nu_\mu, \bar{\nu}_\mu$ differential and total QE cross sections for nucleons bound in carbon. The $Q^2$ dependence of the transverse enhancement is observed to resolve much of the long standing discrepancy in the QE total cross sections and differential distributions between low energy and high energy neutrino experiments on nuclear targets.Comment: Revised Version- July 21, 2011: 17 pages, 20 Figures. To be published in Eur. Phys. J.

Methods to Determine Neutrino Flux at Low Energies:Investigation of the Low ν\nu Method

We investigate the "low-$\nu$" method (developed by the CCFR/NUTEV collaborations) to determine the neutrino flux in a wide band neutrino beam at very low energies, a region of interest to neutrino oscillations experiments. Events with low hadronic final state energy $\nu<\nu_{cut}$ (of 1, 2 and 5 GeV) were used by the MINOS collaboration to determine the neutrino flux in their measurements of neutrino ($\nu_\mu$) and antineutrino (\nub_\mu) total cross sections. The lowest $\nu_\mu$ energy for which the method was used in MINOS is 3.5 GeV, and the lowest \nub_\mu energy is 6 GeV. At these energies, the cross sections are dominated by inelastic processes. We investigate the application of the method to determine the neutrino flux for $\nu_\mu$, \nub_\mu energies as low as 0.7 GeV where the cross sections are dominated by quasielastic scattering and $\Delta$(1232) resonance production. We find that the method can be extended to low energies by using $\nu_{cut}$ values of 0.25 and 0.50 GeV, which is feasible in fully active neutrino detectors such as MINERvA.Comment: 25 pages, 32 figures, to be published in European Physics Journal

First Observation of Coherent π0\pi^0 Production in Neutrino Nucleus Interactions with Eν<E_{\nu}< 2 GeV

The MiniBooNE experiment at Fermilab has amassed the largest sample to date of $\pi^0$s produced in neutral current (NC) neutrino-nucleus interactions at low energy. This paper reports a measurement of the momentum distribution of $\pi^0$s produced in mineral oil (CH$_2$) and the first observation of coherent $\pi^0$ production below 2 GeV. In the forward direction, the yield of events observed above the expectation for resonant production is attributed primarily to coherent production off carbon, but may also include a small contribution from diffractive production on hydrogen. Integrated over the MiniBooNE neutrino flux, the sum of the NC coherent and diffractive modes is found to be (19.5 $\pm$1.1 (stat) $\pm$2.5 (sys))% of all exclusive NC $\pi^0$ production at MiniBooNE. These measurements are of immediate utility because they quantify an important background to MiniBooNE's search for $\nu_{\mu} \to \nu_e$ oscillations.Comment: Submitted to Phys. Lett.

Limit on Bs0B^0_s oscillation using a jet charge method

A lower limit is set on the B_{s}^{0} meson oscillation parameter \Delta m_{s} using data collected from 1991 to 1994 by the ALEPH detector. Events with a high transverse momentum lepton and a reconstructed secondary vertex are used. The high transverse momentum leptons are produced mainly by b hadron decays, and the sign of the lepton indicates the particle/antiparticle final state in decays of neutral B mesons. The initial state is determined by a jet charge technique using both sides of the event. A maximum likelihood method is used to set a lower limit of \, \Delta m_{s}. The 95\% confidence level lower limit on \Delta m_s ranges between 5.2 and 6.5(\hbar/c^{2})~ps^{-1} when the fraction of b quarks from Z^0 decays that form B_{s}^{0} mesons is varied from 8\% to 16\%. Assuming that the B_{s}^{0} fraction is 12\%, the lower limit would be \Delta m_{s} 6.1(\hbar/c^{2})~ps^{-1} at 95\% confidence level. For x_s = \Delta m_s \, \tau_{B_s}, this limit also gives x_s 8.8 using the B_{s}^{0} lifetime of \tau_{B_s} = 1.55 \pm 0.11~ps and shifting the central value of \tau_{B_s} down by 1\sigma

Measurement of the Bs0^0_s lifetime and production rate with Ds−l+^-_s l^+ combinations in Z decays

The lifetime of the \bs meson is measured in approximately 3 million hadronic Z decays accumulated using the ALEPH detector at LEP from 1991 to 1994. Seven different \ds decay modes were reconstructed and combined with an opposite sign lepton as evidence of semileptonic \bs decays. Two hundred and eight \dsl candidates satisfy selection criteria designed to ensure precise proper time reconstruction and yield a measured \bs lifetime of \mbox{\result .} Using a larger, less constrained sample of events, the product branching ratio is measured to be \mbox{\pbrresult