The influence of waiting times and sociopolitical variables on public trust in healthcare: A cross-sectional study of the NHS in England

Objectives This study aims to assess factors influencing public trust in the National Health Service (NHS) in England, focusing on the impact of waiting times in Accident and Emergency (A and E) departments and for GP-to-specialist cancer referrals. Study design A cross-sectional survey-based research design was employed, covering the period from July 2022 to July 2023. Methods Data were collected through YouGov surveys, yielding 7415 responses. Our analysis is based on 6952 of these responses which we were able to aggregate to 42 NHS Integrated Care Boards (ICBs) for A and E waiting times and 106 ICB sub-units for cancer referral times. Multiple regression analysis was conducted, with the dependent variable being trust in the NHS. Results Waiting times for A and E and cancer referrals did not significantly affect trust in the NHS. However, other sociopolitical factors displayed significant influence. Specifically, being a member of an ethnic minority group, or having voted Conservative in the 2019 general election were associated with lower trust scores. Other variables such as age and local unemployment rate were also significant predictors. Conclusions Our findings suggest that waiting times for healthcare services have no effect on public trust in the NHS. Instead, trust appears to be largely shaped by sociopolitical factors. Policymakers should therefore look beyond operational efficiency when seeking to bolster trust in the healthcare system

Synergism through WEE1 and CHK1 inhibition in acute lymphoblastic leukemia

Introduction: Screening for synthetic lethality markers has demonstrated that the inhibition of the cell cycle checkpoint kinases WEE1 together with CHK1 drastically affects stability of the cell cycle and induces cell death in rapidly proliferating cells. Exploiting this finding for a possible therapeutic approach has showed efficacy in various solid and hematologic tumors, though not specifically tested in acute lymphoblastic leukemia. Methods: The efficacy of the combination between WEE1 and CHK1 inhibitors in B and T cell precursor acute lymphoblastic leukemia (B/T-ALL) was evaluated in vitro and ex vivo studies. The efficacy of the therapeutic strategy was tested in terms of cytotoxicity, induction of apoptosis, and changes in cell cycle profile and protein expression using B/T-ALL cell lines. In addition, the efficacy of the drug combination was studied in primary B-ALL blasts using clonogenic assays. Results: This study reports, for the first time, the efficacy of the concomitant inhibition of CHK1/CHK2 and WEE1 in ALL cell lines and primary leukemic B-ALL cells using two selective inhibitors: PF-0047736 (CHK1/CHK2 inhibitor) and AZD-1775 (WEE1 inhibitor). We showed strong synergism in the reduction of cell viability, proliferation and induction of apoptosis. The efficacy of the combination was related to the induction of early S-phase arrest and to the induction of DNA damage, ultimately triggering cell death. We reported evidence that the efficacy of the combination treatment is independent from the activation of the p53-p21 pathway. Moreover, gene expression analysis on B-ALL primary samples showed that Chek1 and Wee1 are significantly co-expressed in samples at diagnosis (Pearson r = 0.5770, p = 0.0001) and relapse (Pearson r= 0.8919; p = 0.0001). Finally, the efficacy of the combination was confirmed by the reduction in clonogenic survival of primary leukemic B-ALL cells. Conclusion: Our findings suggest that the combination of CHK1 and WEE1 inhibitors may be a promising therapeutic strategy to be tested in clinical trials for adult ALL

Efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma not receiving inhaled corticosteroids

Background: Asthma is a heterogeneous and complex disease in both its clinical course and response to treatment. IL-13 is central to Type 2 inflammation and contributes to many features of asthma. In a previous Phase 2 study, lebrikizumab, an anti-IL-13 monoclonal antibody, did not significantly improve FEV1 in mild-to-moderate asthma patients not receiving ICS therapy. This Phase 3 study was designed to further assess the efficacy and safety of lebrikizumab in adult patients with mild-to-moderate asthma treated with daily short-acting β2-agonist therapy alone. Methods: Adult patients with mild-to-moderate asthma were randomised to receive lebrikizumab 125 mg subcutaneously (SC), placebo SC, or montelukast 10 mg orally for 12 weeks, with an 8-week follow-up period. The primary efficacy endpoint was absolute change in pre-bronchodilator FEV1 from baseline at Week 12. Findings: A total of 310 patients were randomised and dosed in the study. The mean absolute change in FEV1 from baseline at Week 12 was higher in the lebrikizumab-treated arm compared with placebo (150 mL versus 67 mL); however, this improvement did not achieve statistical significance (overall adjusted difference of 83 mL [95% CI:-3, 170]; p = .06). Montelukast did not improve FEV1 as compared with placebo. Lebrikizumab was generally safe and well tolerated during the study. Interpretation: Lebrikizumab did not significantly improve FEV1 in mild-to-moderate asthma patients at a dose expected to inhibit the IL-13 pathway. Inhibiting IL-13 in this patient population was not sufficient to improve lung function. These data support the findings of a previous trial of lebrikizumab in patients not receiving ICS

EFFECT OF CORTISOL TREATMENT ON HORMONAL RELATIONSHIPS IN CONGENITAL ADRENAL HYPERPLASIA

The temporal relationship between administration of cortisol and serum 17Α-hydroxyprogesterone was investigated in five patients aged 9-19 years with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. There was marked variability in the 17Α-hydroxyprogesterone response (determined hourly for 24 h) of individual patients to administration of cortisol. Mean concentration was less than 0.030 Μmol/l in one patient but 0.519Μ mol/l in another. Levels were higher in all patients while off treatment, and were greatest in those with salt-losing adrenal hyperplasia. Growth hormone secretion was not suppressed by treatment with cortisol. Withdrawal of cortisol for 3 days resulted in a significant decrease in the mean serum FSH/LH ratio and a rise in serum testosterone in all subjects. Episodic release of gonadotrophins persisted in the adolescent patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75713/1/j.1365-2265.1977.tb02002.x.pd

Measurement of the p-pbar -> Wgamma + X cross section at sqrt(s) = 1.96 TeV and WWgamma anomalous coupling limits

The WWgamma triple gauge boson coupling parameters are studied using p-pbar -> l nu gamma + X (l = e,mu) events at sqrt(s) = 1.96 TeV. The data were collected with the DO detector from an integrated luminosity of 162 pb^{-1} delivered by the Fermilab Tevatron Collider. The cross section times branching fraction for p-pbar -> W(gamma) + X -> l nu gamma + X with E_T^{gamma} > 8 GeV and Delta R_{l gamma} > 0.7 is 14.8 +/- 1.6 (stat) +/- 1.0 (syst) +/- 1.0 (lum) pb. The one-dimensional 95% confidence level limits on anomalous couplings are -0.88 < Delta kappa_{gamma} < 0.96 and -0.20 < lambda_{gamma} < 0.20.Comment: Submitted to Phys. Rev. D Rapid Communication

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt{s} = 1.96 TeV using Kinematic Characteristics of Lepton + Jets Events

We present a measurement of the top quark pair ttbar production cross section in ppbar collisions at a center-of-mass energy of 1.96 TeV using 230 pb**{-1} of data collected by the DO detector at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), large missing transverse energy, and at least four jets, and extract the ttbar content of the sample based on the kinematic characteristics of the events. For a top quark mass of 175 GeV, we measure sigma(ttbar) = 6.7 {+1.4-1.3} (stat) {+1.6- 1.1} (syst) +/-0.4 (lumi) pb, in good agreement with the standard model prediction.Comment: submitted to Phys.Rev.Let

Measurement of the ttbar Production Cross Section in ppbar Collisions at sqrt(s)=1.96 TeV using Lepton + Jets Events with Lifetime b-tagging

We present a measurement of the top quark pair ($t\bar{t}$) production cross section ($\sigma_{t\bar{t}}$) in $p\bar{p}$ collisions at $\sqrt{s}=1.96$ TeV using 230 pb$^{-1}$ of data collected by the D0 experiment at the Fermilab Tevatron Collider. We select events with one charged lepton (electron or muon), missing transverse energy, and jets in the final state. We employ lifetime-based b-jet identification techniques to further enhance the $t\bar{t}$ purity of the selected sample. For a top quark mass of 175 GeV, we measure $\sigma_{t\bar{t}}=8.6^{+1.6}_{-1.5}(stat.+syst.)\pm 0.6(lumi.)$ pb, in agreement with the standard model expectation.Comment: 7 pages, 2 figures, 3 tables Submitted to Phys.Rev.Let

Measurement of the Isolated Photon Cross Section in p-pbar Collisions at sqrt{s}=1.96 TeV

The cross section for the inclusive production of isolated photons has been measured in p anti-p collisions at sqrt{s}=1.96 TeV with the D0 detector at the Fermilab Tevatron Collider. The photons span transverse momenta 23 to 300 GeV and have pseudorapidity |eta|<0.9. The cross section is compared with the results from two next-to-leading order perturbative QCD calculations. The theoretical predictions agree with the measurement within uncertainties.Comment: 7 pages, 5 figures, submitted to Phys.Lett.