Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer.

IMPORTANCE: Pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed. OBJECTIVE: To estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs. DESIGN, SETTING, AND PARTICIPANTS: In this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed. EXPOSURES: CSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention. MAIN OUTCOMES AND MEASURES: The incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated. RESULTS: In the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were -£1942/QALY (-$2680/QALY), -£89/QALY (-$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs. CONCLUSIONS AND RELEVANCE: In this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management

From START to FINISH : the influence of osmotic stress on the cell cycle

Peer reviewedPublisher PD

Correlates of Complete Childhood Vaccination in East African Countries.

Despite the benefits of childhood vaccinations, vaccination rates in low-income countries (LICs) vary widely. Increasing coverage of vaccines to 90% in the poorest countries over the next 10 years has been estimated to prevent 426 million cases of illness and avert nearly 6.4 million childhood deaths worldwide. Consequently, we sought to provide a comprehensive examination of contemporary vaccination patterns in East Africa and to identify common and country-specific barriers to complete childhood vaccination. Using data from the Demographic and Health Surveys (DHS) for Burundi, Ethiopia, Kenya, Rwanda, Tanzania, and Uganda, we looked at the prevalence of complete vaccination for polio, measles, Bacillus Calmette-Guérin (BCG) and DTwPHibHep (DTP) as recommended by the WHO among children ages 12 to 23 months. We conducted multivariable logistic regression within each country to estimate associations between complete vaccination status and health care access and sociodemographic variables using backwards stepwise regression. Vaccination varied significantly by country. In all countries, the majority of children received at least one dose of a WHO recommended vaccine; however, in Ethiopia, Tanzania, and Uganda less than 50% of children received a complete schedule of recommended vaccines. Being delivered in a public or private institution compared with being delivered at home was associated with increased odds of complete vaccination status. Sociodemographic covariates were not consistently associated with complete vaccination status across countries. Although no consistent set of predictors accounted for complete vaccination status, we observed differences based on region and the location of delivery. These differences point to the need to examine the historical, political, and economic context of each country in order to maximize vaccination coverage. Vaccination against these childhood diseases is a critical step towards reaching the Millennium Development Goal of reducing under-five mortality by two-thirds by 2015 and thus should be a global priority

Molecular portrait of high alpha-fetoprotein in hepatocellular carcinoma: implications for biomarker-driven clinical trials

The clinical utility of serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC) is widely recognised. However, a clear understanding of the mechanisms of AFP overexpression and the molecular traits of patients with AFP-high tumours are not known. We assessed transcriptome data, whole-exome sequencing data and DNA methylome profiling of 520 HCC patients from two independent cohorts to identify distinct molecular traits of patients with AFP-high tumours (serum concentration?>?400?ng/ml), which represents an accepted prognostic cut-off and a predictor of response to ramucirumab. Those AFP-high tumours (18% of resected cases) were characterised by significantly lower AFP promoter methylation (p?<?0.001), significant enrichment of progenitor-cell features (CK19, EPCAM), higher incidence of BAP1 oncogene mutations (8.5% vs 1.6%) and lower mutational rates of CTNNB1 (14% vs 30%). Specifically, AFP-high tumours displayed significant activation of VEGF signalling (p?<?0.001), which might provide the rationale for the reported benefit of ramucirumab in this subgroup of patients

Measurement of the eta-Meson Mass using psi(2S) --> eta J/psi

We measure the mass of the eta meson using psi(2S) --> eta J/psi events acquired with the CLEO-c detector operating at the CESR e+e- collider. Using the four decay modes eta --> gamma gamma, 3pi0, pi+pi-pi0, and pi+pi-gamma, we find M(eta)=547.785 +- 0.017 +- 0.057 MeV, in which the first uncertainty is statistical and the second systematic. This result has an uncertainty comparable to the two most precise previous measurements and is consistent with that of NA48, but is inconsistent at the level of 6.5sigma with the much smaller mass obtained by GEM.Comment: 10 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2007/, Submitted to PR

Di-electron Widths of the Upsilon(1S,2S,3S) Resonances

We determine the di-electron widths of the Upsilon(1S), Upsilon(2S), and Upsilon(3S) resonances with better than 2% precision by integrating the cross-section of e+e- -> Upsilon over the e+e- center-of-mass energy. Using e+e- energy scans of the Upsilon resonances at the Cornell Electron Storage Ring and measuring Upsilon production with the CLEO detector, we find di-electron widths of 1.354 +- 0.004 (stat) +- 0.020 (syst) keV, 0.619 +- 0.004 +- 0.010 keV, and 0.446 +- 0.004 +- 0.007 keV for the Upsilon(1S), Upsilon(2S), and Upsilon(3S), respectively.Comment: 9 pages, 4 figures, also available through http://www.lns.cornell.edu/public/CLNS/2005/, published in PRL; corrected numerical values in abstrac

Measurement of \cal{B}(D^+ --> mu^+ nu) and the Pseudoscalar Decay Constant fD+f_{D^+}

In 60 pb-1 of data taken on the psi(3770) resonance with the CLEO-c detector, we find 8 D+ to mu+ nu event candidates that are mostly signal, containing only 1 estimated background. Using this statistically compelling sample, we measure preliminary values of B(D+ to mu+ nu) = (3.5 +- 1.4 +- 0.6)*10^{-4}, and determine f_{D+} =(201+- 41+- 17) MeV.Comment: 17 pages postscript, also available through http://www.lns.cornell.edu/public/CONF/2004/, Presented at ICHEP Aug 16-22,2004, Beijing, Chin

New Measurements of Upsilon(1S) Decays to Charmonium Final States

Using substantially larger data samples collected by the CLEO III detector, we report on new measurements of the decays of Upsilon(1S) to charmonium final states, including J/Psi, psi(2S), and chi_cJ. The latter two are first observations of these decays. We measure the branching fractions as follows: B(Y(1S)--> J/Psi+X)=(6.4+-0.4+-0.6)x10^-4, B(Y(1S)--> psi(2S)+X)/B(Y(1S)--> J/Psi+X)=0.41+-0.11+-0.08, B(Y(1S)--> chi_c1+X)/B(Y(1S)--> J/Psi+X)=0.35+-0.08+-0.06, B(Y(1S)--> chi_c2+X)/B(Y(1S)--> J/Psi+X)=0.52+-0.12+-0.09, and B(Y(1S)--> chi_c0+X)/B(Y(1S)--> J/Psi+X)<7.4% at 90% confidence level. We also report on the momentum and angular spectra of J/Psi's in Upsilon(1S) decay. The results are compared to predictions of the color octet and color singlet models.Comment: 27 pages postscript,also available through http://w4.lns.cornell.edu/public/CLNS/, submitted to PR

Update of the measurement of the cross section for e^+e^- -> psi(3770) -> hadrons

We have updated our measurement of the cross section for e^+e^- -> psi(3770) -> hadrons, our publication "Measurement of sigma(e^+e^- -> psi(3770) -> hadrons) at E_{c.m.} = 3773 MeV", arXiv:hep-ex/0512038, Phys.Rev.Lett.96, 092002 (2006). Simultaneous with this arXiv update, we have published an erratum in Phys.Rev.Lett.104, 159901 (2010). There, and in this update, we have corrected a mistake in the computation of the error on the difference of the cross sections for e^+e^- -> psi(3770) -> hadrons and e^+e^- -> psi(3770) -> DDbar. We have also used a more recent CLEO measurement of cross section for e^+e^- -> psi(3770) -> DDbar. From this, we obtain an upper limit on the branching fraction for psi(3770) -> non-DDbar of 9% at 90% confidence level.Comment: 3 pages, 0 figures. This is an erratum to Phys.Rev.Lett.96:092002,2006. Added a reference

The Search for eta(1440) --> K^0_S K^pm \pi^mp in Two-Photon Fusion at CLEO

We analyze 13.8 \rm fb^{-1} of the integrated e^+e^- luminosity collected at 10.6 GeV center-of-mass energy with the CLEO II and CLEO II.V detectors to study exclusive two-photon production of hadrons with masses below 1.7{\rm \ GeV/c^2} decaying into the K^0_S K^\pm \pi^\mp final state. We observe two statistically significant enhancements in the \eta(1440) mass region. These enhancements have large transverse momentum which rules them out as being due to pseudoscalar resonances but is consistent with the production of axial-vector mesons. We use tagged two-photon events to study the properties of the observed enhancements and associate them with the production of f_1(1285) and f_1(1420). Our non-observation of \eta(1440) is inconsistent by more than two standard deviations with the first observation of this resonance in two-photon collisions by the L3 experiment. We present our estimates for 90% confidence level upper limits on the products of two-photon partial widths of pseudoscalar hadrons and their branching fractions into K^0_S(\pi^+\pi^-)K^\pm\pi^\mp.Comment: 24 pages postscript,also available through http://www.lns.cornell.edu/public/CLNS/2004/, submitted to PR