Testing many treatments within a single protocol over 10 years at MRC Clinical Trials Unit at UCL: Multi-arm, multi-stage platform, umbrella and basket protocols

There is real need to change how we do some of our clinical trials, as currently the testing and development process is too slow, too costly and too failure-prone often we find that a new treatment is no better than the current standard. Much of the focus on the development and testing pathway has been in improving the design of phase I and II trials. In this article, we present examples of new methods for improving the design of phase III trials (and the necessary lead up to them) as they are the most time-consuming and expensive part of the pathway. Key to all these methods is the aim to test many treatments and/or pose many therapeutic questions within one protocol

Having a lot of a good thing: multiple important group memberships as a source of self-esteem.

Copyright: © 2015 Jetten et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedMembership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem.This study was supported by 1. Australian Research Council Future Fellowship (FT110100238) awarded to Jolanda Jetten (see http://www.arc.gov.au) 2. Australian Research Council Linkage Grant (LP110200437) to Jolanda Jetten and Genevieve Dingle (see http://www.arc.gov.au) 3. support from the Canadian Institute for Advanced Research Social Interactions, Identity and Well-Being Program to Nyla Branscombe, S. Alexander Haslam, and Catherine Haslam (see http://www.cifar.ca)

A restrictive versus liberal transfusion strategy to prevent myocardial injury in patients undergoing surgery for fractured neck of femur:a feasibility randomised controlled trial (RESULT-NOF)

BackgroundThe optimum transfusion strategy in patients with fractured neck of femur is uncertain, particularly if there is coexisting cardiovascular disease. MethodsWe conducted a prospective, single-centre, randomised feasibility trial of two transfusion strategies. We randomly assigned patients undergoing surgery for fractured neck of femur to a restrictive (haemoglobin, 70–90 g L −1) or liberal (haemoglobin, 90–110 g L −1) transfusion strategy throughout their hospitalisation. Feasibility outcomes included: enrolment rate, protocol compliance, difference in haemoglobin, and blood exposure. The primary clinical outcome was myocardial injury using troponin estimations. Secondary outcomes included major adverse cardiac events, postoperative complications, duration of hospitalisation, mortality, and quality of life. ResultsWe enrolled 200 (22%) of 907 eligible patients, and 62 (31%) showed decreased haemoglobin (to 90 g L −1 or less) and were thus exposed to the intervention. The overall protocol compliance was 81% in the liberal group and 64% in the restrictive group. Haemoglobin concentrations were similar preoperatively and at postoperative day 1 but lower in the restrictive group on day 2 (mean difference [MD], 7.0 g L −1; 95% confidence interval [CI], 1.6–12.4). Lowest haemoglobin within 30 days/before discharge was lower in the restrictive group (MD, 5.3 g L −1; 95% CI, 1.7–9.0). Overall, 58% of patients in the restrictive group received no transfusion compared with 4% in the liberal group (difference in proportion, 54.5%; 95% CI, 36.8–72.2). The proportion with the primary clinical outcome was 14/26 (54%, liberal) vs 24/34 (71%, restrictive), and the difference in proportion was –16.7% (95% CI, –41.3 to 7.8; P=0.18). ConclusionA clinical trial of two transfusion strategies in hip fracture with a clinically relevant cardiac outcome is feasible

Magnetic resonance imaging during a pandemic: recommendations by the ISMRM Safety Committee

The COVID-19 pandemic highlighted the challenges delivering face-to-face patient care across healthcare systems. In particular the COVID-19 pandemic challenged the imaging community to provide timely access to essential diagnostic imaging modalities while ensuring appropriate safeguards were in place for both patients and personnel. With increasing vaccine availability and greater prevalence of vaccination in communities worldwide we are finally emerging on the other side of the COVID-19 pandemic. As we learned from our institutional and healthcare system responses to the pandemic, maintaining timely access to MR imaging is essential. Radiologists and other imaging providers partnered with their referring providers to ensure that timely access to advanced MR imaging was maintained. On behalf of the International Magnetic Resonance in Medicine (ISMRM) Safety Committee, this white paper is intended to serve as a guide for radiology departments, imaging centers, and other imaging specialists who perform MR imaging to refer to as we prepare for the next pandemic. Lessons learned including strategies to triage and prioritize MR imaging research during a pandemic are discussed. Level of Evidence 5 Technical Efficacy Stage 5Radiolog

Two successful pregnancies in a woman with chronic myeloid leukemia exposed to nilotinib during the first trimester of her second pregnancy: case study

The occurrence of chronic myeloid leukemia in pregnancy is rare and its management poses a clinical challenge for physicians treating these patients. We report a 30-year-old woman with chronic myeloid leukemia who became pregnant twice successfully. Philadelphia-positive CML in its chronic phase was diagnosed at 16 weeks of her first gestation. At that time, she received no treatment throughout her pregnancy. At 38 weeks of gestation, a normal infant was delivered by cesarean section. At six weeks postpartum, the patient underwent imatinib mesylate therapy but she could not tolerate the treatment. The treatment was then changed to nilotinib at 400 mg orally b.i.d. Two years later, she became pregnant again while she was on nilotinib 200 mg b.i.d. The unplanned pregnancy was identified during her 7.4 weeks of gestation. Because the patient elected to continue her pregnancy, nilotinib was stopped immediately, and no further treatment was given until delivery. Neither obstetrical complications nor structural malformations in neonates in both pregnancies were observed. Both babies' growth and development have been normal. Although this experience is limited to a single patient, the success of this patient demonstrates that the management of chronic myeloid leukemia in pregnant women may be individualized based on the relative risks and benefits of the patient and fetus

Bar-Driven Evolution and 2D Spectroscopy of Bulges

A multi-faceted approach is described to constrain the importance of bar-driven evolution in disk galaxies, particularly bulge formation. N-body simulations are used to construct stellar kinematic bar diagnostics for edge-on systems and to quantify the expected vertical structure of bars, and they are compared to observations of 30 edge-on spirals, most with a boxy bulge. Long-slit spectra of the galaxies show characteristic double-hump rotation curves, dispersion profiles with secondary peaks and/or flat maxima, and correlated h3 and V profiles, indicating that most of them harbor edge-on bars. The presence of cold, quasi-axisymmetric central stellar disks is also suggested, presumably formed through bar-driven gaseous inflow and star formation. K-band imaging of the same galaxies spectacularly highlights radial variations of the bars' scaleheights, as expected from vertical disk instabilities. The light profiles also vary radially in shape but never approach a classic de Vaucouleurs law. Filtering of the images further isolates the specific orbit families at the origin of the boxy structure, which can be directly related to periodic orbit calculations in 3D barred potentials. Bars are thus shown to contribute substantially to the formation of both large-scale triaxial bulges and embedded central disks. Relevant results from the SAURON survey of the stellar/ionized-gas kinematics and stellar populations of spheroids are also described. Examples are used to illustrate the potential of coupling stellar kinematics and linestrengths (age and metallicity), here specifically to unravel the dynamical evolution and related chemical enrichment history of bars and bulges. [Abridged]Comment: 10 pages, including 4 figures (LaTeX, kapproc.cls, procps.sty). To appear in "Penetrating Bars through Masks of Cosmic Dust: the Hubble Tuning Fork Strikes a New Note", eds. D.L. Block, K.C. Freeman, I. Puerari, & R. Groess (Kluwer: Dordrecht). A version with full resolution PostScript figures is available at http://www.astro.columbia.edu/~bureau/Publications/peanut_sa_04.ps.g

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Enabling Multilingual Search through Controlled Vocabularies: the AGRIS Approach

AGRIS is a bibliographic database of scientific publications in the food and agricultural domain. The AGRIS web portal is highly visited, reaching peaks of 350,000 visits/month from more than 200 countries and territories. Considering the variety of AGRIS users, the possibility to support cross-language information retrieval is crucial to improve the usefulness of the web-site. This paper describes a lightweight approach adopted to enable the afore-mentioned feature in the AGRIS system. The proposed approach relies on the adoption of a controlled vocabulary. Furthermore, we discuss how expanding user queries with synonyms increases the sensitivity of a search engine and how we can use a controlled vocabulary to achieve this result

Children's vomiting following posterior fossa surgery: A retrospective study

<p>Abstract</p> <p>Background</p> <p>Nausea and vomiting is a problem for children after neurosurgery and those requiring posterior fossa procedures appear to have a high incidence. This clinical observation has not been quantified nor have risk factors unique to this group of children been elucidated.</p> <p>Methods</p> <p>A six year retrospective chart audit at two Canadian children's hospitals was conducted. The incidence of nausea and vomiting was extracted. Hierarchical multivariable logistic regression was used to quantify risk and protective factors at 120 hours after surgery and early vs. late vomiting.</p> <p>Results</p> <p>The incidence of vomiting over a ten day postoperative period was 76.7%. Documented vomiting ranged from single events to greater than 20 over the same period. In the final multivariable model: adolescents (age 12 to <17) were less likely to vomit by 120 hours after surgery than other age groups; those who received desflurane, when compared to all other volatile anesthetics, were more likely to vomit, yet the use of ondansetron with desflurane decre kelihood. Children who had intraoperative ondansetron were more likely to vomit in the final multivariable model (perhaps because of its use, in the clinical judgment of the anesthesiologist, for children considered at risk). Children who started vomiting in the first 24 hours were more likely to be school age (groups 4 to <7 and 7 to <12) and receive desflurane. Nausea was not well documented and was therefore not analyzed.</p> <p>Conclusion</p> <p>The incidence of vomiting in children after posterior fossa surgery is sufficient to consider all children requiring these procedures to be at high risk for POV. Nausea requires better assessment and documentation.</p