Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis.

Background: Atovaquone/proguanil, registered as Malarone®, is a fixed-dose combination recommended for first-line treatment of uncomplicated Plasmodium falciparum malaria in non-endemic countries and its prevention in travellers. Mutations in the cytochrome bc1 complex are causally associated with atovaquone resistance. Methods: This systematic review assesses the clinical efficacy of atovaquone/proguanil treatment of uncomplicated malaria and examines the extent to which codon 268 mutation in cytochrome b influences treatment failure and recrudescence based on published information. Results: Data suggest that atovaquone/proguanil treatment efficacy is 89%-98% for P. falciparum malaria (from 27 studies including between 18 and 253 patients in each case) and 20%-26% for Plasmodium vivax malaria (from 1 study including 25 patients). The in vitro P. falciparum phenotype of atovaquone resistance is an IC50 value >28 nM. Case report analyses predict that recrudescence in a patient presenting with parasites carrying cytochrome b codon 268 mutation will occur on average at day 29 (95% CI: 22, 35), 19 (95% CI: 7, 30) days longer than if the mutation is absent. Conclusions: Evidence suggests atovaquone/proguanil treatment for P. falciparum malaria is effective. Late treatment failure is likely to be associated with a codon 268 mutation in cytochrome b, though recent evidence from animal models suggests these mutations may not spread within the population. However, early treatment failure is likely to arise through alternative mechanisms, requiring further investigation

The acceleration and storage of radioactive ions for a neutrino factory

The term beta-beam has been coined for the production of a pure beam of electron neutrinos or their antiparticles through the decay of radioactive ions circulating in a storage ring. This concept requires radioactive ions to be accelerated to a Lorentz gamma of 150 for 6He and 60 for 18Ne. The neutrino source itself consists of a storage ring for this energy range, with long straight sections in line with the experiment(s). Such a decay ring does not exist at CERN today, nor does a high-intensity proton source for the production of the radioactive ions. Nevertheless, the existing CERN accelerator infrastructure could be used as this would still represent an important saving for a beta-beam facility. This paper outlines the first study, while some of the more speculative ideas will need further investigations.Comment: Accepted for publication in proceedings of Nufact02, London, 200

Management and outcomes of heart failure patients with CKD: experience from an inter‐disciplinary clinic

Aims CKD‐HF patients suffer excess hospitalization and mortality, often under‐treated with life‐prolonging medications due to fear of worsening renal function and hyperkalaemia. Yet, role of inter‐disciplinary working in improving therapy is unknown, which this study aims to investigate. Methods and results Clinical, biochemical data, and medications at first and last clinic visit were obtained from patient records for 124 patients seen in kidney failure–heart failure clinic (23 March 2017 to 11 April 2019). Medication dose groups (none, low, and high dose), number of RAASi agents, and blood test results were compared between first and last visit in patients with at least two clinic visits (n = 97). Patient characteristics were age 78.5 years (IQR 68.1–84.4 years), male 67.7%, diabetes 51.6%, moderate (45.2%) vs. severe (39.5%) CKD, HF with reduced ejection fraction (HFrEF) (49.2%), follow‐up 234 days (IQR 121–441 days). HFrEF was associated with increased risk of death (adjusted OR 4.49, 95% CI 1.43–14.05; P = 0.01). Distributions of patients according to number of RAASi agents they were on differed between first and last visit (P = 0.03). Dosage was increased in 25.9% for beta‐blockers, 33.0% for ACEi/ARBs, and 17.5% for MRAs. Distributions of patients across MRA dosage groups was different (P = 0.03), with higher proportions on higher dosages at last visit, without significant changes in serum potassium or creatinine. Serum ferritin improved (131.0 vs. 267.5 μg/L; P < 0.001), and fewer patients had iron deficiency (56.7% vs. 26.8%; P = 0.002) at last visit compared to the first. Conclusions This inter‐disciplinary clinic improved guideline‐recommended medication prescription, MRA dosages in CKD‐HF patients without significant biochemical abnormality, and iron status. A prospectively designed study with medication titration protocol and defined patient‐centred outcomes is needed to further assess effectiveness of such clinic

Changing knowledge, attitudes and behaviours towards cytomegalovirus in pregnancy through film-based antenatal education: a feasibility randomised controlled trial of a digital educational intervention

Background Congenital cytomegalovirus (CMV) is the most common congenital infection globally, however information about CMV is not routinely included in antenatal education in the United Kingdom. This feasibility study aimed to gather the essential data needed to design and power a large randomised controlled trial (RCT) to investigate the efficacy of a digital intervention in reducing the risk of CMV acquisition in pregnancy. In order to do this, we carried out a single-centre RCT, which explored the knowledge, attitudes and risk reduction behaviours in women in the intervention and treatment as usual groups, pre- and post-intervention. Methods CMV seronegative women living with a child less than four years old, receiving antenatal care at a single UK tertiary centre, were randomised to the digital intervention or ‘treatment as usual’ groups. Participants completed questionnaires before the digital intervention and after and at 34 gestational weeks, and responses within groups and between groups were compared using tailored randomisation tests. CMV serology was tested in the first trimester and at the end of pregnancy. Results Of the 878 women screened, 865 samples were analysed with 43% (n = 372) being CMV seronegative and therefore eligible to take part in the RCT; of these, 103 (27.7%) women were enrolled and 87 (84%) of these completed the study. Most participants (n = 66; 64%) were unfamiliar with CMV at enrolment, however at 34 gestational weeks, women in the intervention group (n = 51) were more knowledgeable about CMV compared to the treatment as usual group (n = 52) and reported engaging in activities that may increase the risk of CMV transmission less frequently. The digital intervention was highly acceptable to pregnant women. Overall, four participants seroconverted over the course of the study: two from each study group. Conclusions A large multi-centre RCT investigating the efficacy of a CMV digital intervention is feasible in the United Kingdom; this study has generated essential data upon which to power such a study. This single-centre feasibility RCT demonstrates that a digital educational intervention is associated with increase in knowledge about CMV and can result in behaviour change which may reduce the risk of CMV acquisition in pregnancy

Mid-Rapidity Direct-Photon Production in p+p Collisions at sqrt(s) = 200 GeV

A measurement of direct photons in p+p collisions at sqrt(s)=200 GeV is presented. A photon excess above background from pi^0 --> gamma+gamma, eta --> gamma+gamma, and other decays is observed in the transverse momentum range 5.5 < p_T < 7 GeV/c. The result is compared to a next-to-leading-order perturbative QCD calculation. Within errors, good agreement is found between the QCD calculation and the measured result.Comment: 330 authors, 7 pages text, RevTeX, 2 figures, 2 tables. Submitted to Physical Review D. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Suppressed pi^0 Production at Large Transverse Momentum in Central Au+Au Collisions at sqrt(s_NN) = 200 GeV

Transverse momentum spectra of neutral pions in the range 1 < p_T < 10 GeV/c have been measured at mid-rapidity by the PHENIX experiment at RHIC in Au+Au collisions at sqrt(s_NN) = 200 GeV. The pi^0 multiplicity in central reactions is significantly below the yields measured at the same sqrt(s_NN) in peripheral Au+Au and p+p reactions scaled by the number of nucleon-nucleon collisions. For the most central bin, the suppression factor is ~2.5 at p_T = 2 GeV/c and increases to ~4-5 at p_T ~= 4 GeV/c. At larger p_T, the suppression remains constant within errors. The deficit is already apparent in semi-peripheral reactions and increases smoothly with centrality.Comment: 326 authors, 6 pages text, RevTeX, 3 figures, 2 tables. Submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Deuteron and antideuteron production in Au+Au collisions at sqrt(s_NN)=200 GeV

The production of deuterons and antideuterons in the transverse momentum range 1.1 < p_T < 4.3 GeV/c at mid-rapidity in Au + Au collisions at sqrt(s_NN)=200 GeV has been studied by the PHENIX experiment at RHIC. A coalescence analysis comparing the deuteron and antideuteron spectra with those of protons and antiprotons, has been performed. The coalescence probability is equal for both deuterons and antideuterons and increases as a function of p_T, which is consistent with an expanding collision zone. Comparing (anti)proton yields p_bar/p = 0.73 +/- 0.01, with (anti)deuteron yields: d_bar/d = 0.47 +/- 0.03, we estimate that n_bar/n = 0.64 +/- 0.04.Comment: 326 authors, 6 pages text, 5 figures, 1 Table. Submitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm

Scaling properties of proton and anti-proton production in sqrt(s_NN) = 200 GeV Au + Au collisions

We report on the yield of protons and anti-protons, as a function of centrality and transverse momentum, in Au+Au collisions at sqrt(s_NN) = 200 GeV measured at mid-rapidity by the PHENIX experiment at RHIC. In central collisions at intermediate transverse momenta (1.5 < p_T < 4.5 GeV/c) a significant fraction of all produced particles are protons and anti-protons. They show a centrality-scaling behavior different from that of pions. The p-bar/pion and p/pion ratios are enhanced compared to peripheral Au+Au, p+p, and electron+positron collisions. This enhancement is limited to p_T < 5 GeV/c as deduced from the ratio of charged hadrons to pi^0 measured in the range 1.5 < p_T < 9 GeV/c.Comment: 325 authors, 6 pages text, 4 figures, RevTeX 4. Minor changes to text and figures to meet PRL length restrictions; no changes to figures; resubmitted to PRL. Plain text data tables for the points plotted in figures for this and previous PHENIX publications are (or will be) publicly available at http://www.phenix.bnl.gov/papers.htm