Variation in use of the 2-week referral pathway for suspected cancer: cross-sectional analysis

Background: A 2-Week Wait (2WW) referral pathway for earlier diagnosis of suspected cancer was introduced in England in 2000. Nevertheless, a significant proportion of patients with cancer are diagnosed by other routes (detection rate), only a small proportion of 2WW referrals have cancer (conversion rate) and there is considerable between-practice variation. Aim: This study examined use by practices of the 2WW referral in relation to all cancer diagnoses. Design and setting: A cross-sectional analysis of data extracted from the Cancer Waiting Times Database for all 2WW referrals in 2009 and for all patients receiving a first definitive treatment in the same year. Method: The age standardised referral ratio, conversion rate, and detection rate were calculated for all practices in England and the correlation coefficient for each pair of measures. The median detection rate was calculated for each decile of practices ranked by conversion rate and vice versa, performing nonparametric tests for trend in each case. Results: Data for 8049 practices, 865 494 referrals, and 224 984 cancers were analysed. There were significant correlations between referral ratio and conversion rate (inverse) and detection rate (direct). There was also a direct correlation between conversion and detection rates. There was a significant trend in conversion rate for deciles of detection rate, and vice versa, with a marked difference between the lowest and higher deciles. Conclusion: There is a consistent relationship between 2WW referral conversion rate and detection rate that can be interpreted as representing quality of clinical practice. The 2WW referral rate should not be a measure of quality of clinical care

Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and validation using primary care data from the UK.

OBJECTIVE: To develop and validate a prognostic model to inform risk stratified decisions on frequency of monitoring blood tests during long term methotrexate treatment. DESIGN: Retrospective cohort study. SETTING: Electronic health records within the UK's Clinical Practice Research Datalink (CPRD) Gold and CPRD Aurum. PARTICIPANTS: Adults (≥18 years) with a diagnosis of an immune mediated inflammatory disease who were prescribed methotrexate by their general practitioner for six months or more during 2007-19. MAIN OUTCOME MEASURE: Discontinuation of methotrexate owing to abnormal monitoring blood test result. Patients were followed-up from six months after their first prescription for methotrexate in primary care to the earliest of outcome, drug discontinuation for any other reason, leaving the practice, last data collection from the practice, death, five years, or 31 December 2019. Cox regression was performed to develop the risk equation, with bootstrapping used to shrink predictor effects for optimism. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination. RESULTS: Data from 13 110 (854 events) and 23 999 (1486 events) participants were included in the development and validation cohorts, respectively. 11 candidate predictors (17 parameters) were included. In the development dataset, the optimism adjusted R2 was 0.13 and the optimism adjusted Royston D statistic was 0.79. The calibration slope and Royston D statistic in the validation dataset for the entire follow-up period was 0.94 (95% confidence interval 0.85 to 1.02) and 0.75 (95% confidence interval 0.67 to 0.83), respectively. The prognostic model performed well in predicting outcomes in clinically relevant subgroups defined by age group, type of immune mediated inflammatory disease, and methotrexate dose. CONCLUSION: A prognostic model was developed and validated that uses information collected during routine clinical care and may be used to risk stratify the frequency of monitoring blood test during long term methotrexate treatment

Observation of a Narrow Resonance of Mass 2.46 GeV/c^2 Decaying to D_s^*+ pi^0 and Confirmation of the D_sJ^* (2317) State

Using 13.5 inverse fb of e+e- annihilation data collected with the CLEO II detector we have observed a narrow resonance in the Ds*+pi0 final state, with a mass near 2.46 GeV. The search for such a state was motivated by the recent discovery by the BaBar Collaboration of a narrow state at 2.32 GeV, the DsJ*(2317)+ that decays to Ds+pi0. Reconstructing the Ds+pi0 and Ds*+pi0 final states in CLEO data, we observe peaks in both of the corresponding reconstructed mass difference distributions, dM(Dspi0)=M(Dspi0)-M(Ds) and dM(Ds*pi0)=M(Ds*pi0)-M(Ds*), both of them at values near 350 MeV. We interpret these peaks as signatures of two distinct states, the DsJ*(2317)+ plus a new state, designated as the DsJ(2463)+. Because of the similar dM values, each of these states represents a source of background for the other if photons are lost, ignored or added. A quantitative accounting of these reflections confirms that both states exist. We have measured the mean mass differences = 350.0 +/- 1.2 [stat] +/- 1.0 [syst] MeV for the DsJ*(2317) state, and = 351.2 +/- 1.7 [stat] +/- 1.0 [syst] MeV for the new DsJ(2463)+ state. We have also searched, but find no evidence, for decays of the two states via the channels Ds*+gamma, Ds+gamma, and Ds+pi+pi-. The observations of the two states at 2.32 and 2.46 GeV, in the Ds+pi0 and Ds*+pi0 decay channels respectively, are consistent with their interpretations as (c anti-strange) mesons with orbital angular momentum L=1, and spin-parities of 0+ and 1+.Comment: 16 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, version to be published in Physical Review D; minor modifications and fixes to typographical errors, plus an added section on production properties. The main results are unchanged; they supersede those reported in hep-ex/030501

Measurement of the Charge Asymmetry in B→K∗(892)±π∓B\to K^* (892)^{\pm}\pi^{\mp}

We report on a search for a CP-violating asymmetry in the charmless hadronic decay B -> K*(892)+- pi-+, using 9.12 fb^-1 of integrated luminosity produced at \sqrt{s}=10.58 GeV and collected with the CLEO detector. We find A_{CP}(B -> K*(892)+- pi-+) = 0.26+0.33-0.34(stat.)+0.10-0.08(syst.), giving an allowed interval of [-0.31,0.78] at the 90% confidence level.Comment: 7 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Search for CP Violation in D^0--> K_S^0 pi^+pi^-

We report on a search for CP violation in the decay of D0 and D0B to Kshort pi+pi-. The data come from an integrated luminosity of 9.0 1/fb of e+e- collisions at sqrt(s) ~ 10 GeV recorded with the CLEO II.V detector. The resonance substructure of this decay is well described by ten quasi-two-body decay channels (K*-pi+, K*0(1430)-pi+, K*2(1430)-pi+, K*(1680)-pi+, Kshort rho, Kshort omega, Kshort f0(980), Kshort f2(1270), Kshort f0(1370), and the ``wrong sign'' K*+ pi-) plus a small non-resonant component. We observe no evidence for CP violation in the amplitudes and phases that describe the decay D0 to K_S^0 pi+pi-.Comment: 10 pages, 3 figures, also available at http://w4.lns.cornell.edu/public/CLNS/, submitted to PR

Measurement of Lepton Momentum Moments in the Decay bar{B} \to X \ell \bar{\nu} and Determination of Heavy Quark Expansion Parameters and |V_cb|

We measure the primary lepton momentum spectrum in B-bar to X l nu decays, for p_l > 1.5 GeV/c in the B rest frame. From this, we calculate various moments of the spectrum. In particular, we find R_0 = [int(E_l>1.7) (dGam/dE_sl)*dE_l] / [int(E_l>1.5) (dGam/dE_sl)*dE_l] = 0.6187 +/- 0.0014_stat +/- 0.0016_sys and R_1 = [int(E_l>1.5) E_l(dGam/dE_sl)*dE_l] / [int(E_l>1.5) (dGam/dE_sl)*dE_l] = (1.7810 +/- 0.0007_stat +/- 0.0009_sys) GeV. We use these moments to determine non-perturbative parameters governing the semileptonic width. In particular, we extract the Heavy Quark Expansion parameters Lambda-bar = (0.39 +/- 0.03_stat +/- 0.06_sys +/- 0.12_th) GeV and lambda_1 = (-0.25 +/- 0.02_stat +/- 0.05_sys +/- 0.14_th) GeV^2. The theoretical constraints used are evaluated through order 1/M_B^3 in the non-perturbative expansion and beta_0*alpha__s^2 in the perturbative expansion. We use these parameters to extract |V_cb| from the world average of the semileptonic width and find |V_cb| = (40.8 +/- 0.5_Gam-sl +/- 0.4_(lambda_1,Lambda-bar)-exp +/- 0.9_th) x 10^-3. In addition, we extract the short range b-quark mass m_b^1S = (4.82 +/- 0.07_exp +/- 0.11_th) GeV/c^2. Finally, we discuss the implications of our measurements for the theoretical understanding of inclusive semileptonic processes.Comment: 21 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

First Observation of a Upsilon(1D) State

We present the first evidence for the production of Upsilon(1D) states in the four-photon cascade, Upsilon(3S)-->gamma chib(2P), chib(2P)-->gamma Upsilon(1D), Upsilon(1D)-->gamma chib(1P), chib(1P)-->gamma Upsilon(1S), followed by the Upsilon(1S) annihilation into e+e- or mu+mu-. The signal has a significance of 10.2 standard deviations. The measured product branching ratio for these five decays, (2.5+-0.5+-0.5)x10^(-5), is consistent with the theoretical estimates. The data are dominated by the production of one Upsilon(1D) state consistent with the J=2 assignment. Its mass is determined to be (10161.1+-0.6+-1.6) MeV, which is consistent with the predictions from potential models and lattice QCD calculations. We also searched for Upsilon(3S)-->gammachib(2P), chib(2P)-->gammaUpsilon(1D), followed by either Upsilon(1D)-->eta Upsilon(1S) or Upsilon(1D)-->pi+pi- Upsilon(1S). We find no evidence for such decays and set upper limits on the product branching ratios.Comment: 12 pages postscript,also available through this http://w4.lns.cornell.edu/public/CLNS/, submitted to PR

Search for leptophobic Z ' bosons decaying into four-lepton final states in proton-proton collisions at root s=8 TeV

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