Studying a disease with no home - lessons in trial recruitment from the PATCH II study

<p>Abstract</p> <p>Background</p> <p>Cellulitis is a very common condition that often recurs. The PATCH II study was designed to explore the possibility of preventing future episodes of cellulitis, with resultant cost savings for the NHS. This was the first trial to be undertaken by the UK Dermatology Clinical Trials Network. As such, it was the first to test a recruitment model that involved many busy clinicians each contributing just a few patients.</p> <p>Methods</p> <p>A double-blind randomised controlled trial comparing prophylactic antibiotics (penicillin V) with placebo tablets, for the prevention of repeat episodes of cellulitis of the leg. Primary outcome was time to subsequent recurrence of cellulitis.</p> <p>Results</p> <p>The PATCH II study was closed to recruitment having enrolled 123 participants from a target of 400. Whilst the recruitment period was extended by 12 months, it was not possible to continue beyond this point without additional funds. Many factors contributed to poor recruitment: (i) changes in hospital policy and the introduction of community-based intravenous teams resulted in fewer cellulitis patients being admitted to hospital; ii) those who were admitted were seen by many different specialties, making it difficult for a network of dermatology clinicians to identify suitable participants; and iii) funding for research staff was limited to a trial manager and a trial administrator at the co-ordinating centre. With no dedicated research nurses at the recruiting centres, it was extremely difficult to maintain momentum and interest in the study. Attempts to boost recruitment by providing some financial support for principal investigators to employ local research staff was of limited success.</p> <p>Discussion</p> <p>The model of a network of busy NHS clinicians all recruiting a few patients into large clinical studies requires further testing. It did not work very well for PATCH II, but this was probably because patients were not routinely seen by dermatologists, and recruitment took place prior to research support being available through the Comprehensive Clinical Research Network (CCRN). There is a balance to be struck between asking a lot of centres to recruit just a few patients, and asking a few centres to recruit a lot of patients. Giving modest funds to principal investigators to buy local research nurse time did not work well, probably because too little research time was bought, and it was difficult to separate research tasks from the nurses existing clinical duties. National research infrastructure networks such as the Comprehensive Clinical Research Network will overcome many of the problems encountered in the PATCH II trial.</p> <p>Trial Registration</p> <p>The trial registration number is ISRCTN03813200.</p

Under pressure: Response urgency modulates striatal and insula activity during decision-making under risk

When deciding whether to bet in situations that involve potential monetary loss or gain (mixed gambles), a subjective sense of pressure can influence the evaluation of the expected utility associated with each choice option. Here, we explored how gambling decisions, their psychophysiological and neural counterparts are modulated by an induced sense of urgency to respond. Urgency influenced decision times and evoked heart rate responses, interacting with the expected value of each gamble. Using functional MRI, we observed that this interaction was associated with changes in the activity of the striatum, a critical region for both reward and choice selection, and within the insula, a region implicated as the substrate of affective feelings arising from interoceptive signals which influence motivational behavior. Our findings bridge current psychophysiological and neurobiological models of value representation and action-programming, identifying the striatum and insular cortex as the key substrates of decision-making under risk and urgency

Risk factors for delayed presentation and referral of symptomatic cancer: Evidence for common cancers

Background:It has been suggested that the known poorer survival from cancer in the United Kingdom, compared with other European countries, can be attributed to more advanced cancer stage at presentation. There is, therefore, a need to understand the diagnostic process, and to ascertain the risk factors for increased time to presentation.Methods:We report the results from two worldwide systematic reviews of the literature on patient-mediated and practitioner-mediated delays, identifying the factors that may influence these.Results:Across cancer sites, non-recognition of symptom seriousness is the main patient-mediated factor resulting in increased time to presentation. There is strong evidence of an association between older age and patient delay for breast cancer, between lower socio-economic status and delay for upper gastrointestinal and urological cancers and between lower education level and delay for breast and colorectal cancers. Fear of cancer is a contributor to delayed presentation, while sanctioning of help seeking by others can be a powerful mediator of reduced time to presentation. For practitioner delay, ‘misdiagnosis’ occurring either through treating patients symptomatically or relating symptoms to a health problem other than cancer, was an important theme across cancer sites. For some cancers, this could also be linked to inadequate patient examination, use of inappropriate tests or failing to follow-up negative or inconclusive test results.Conclusion:Having sought help for potential cancer symptoms, it is therefore important that practitioners recognise these symptoms, and examine, investigate and refer appropriately. © 2009 Cancer Research UK All rights reserved

Electroweak Baryogenesis and Dark Matter with an approximate R-symmetry

It is well known that R-symmetric models dramatically alleviate the SUSY flavor and CP problems. We study particular modifications of existing R-symmetric models which share the solution to the above problems, and have interesting consequences for electroweak baryogenesis and the Dark Matter (DM) content of the universe. In particular, we find that it is naturally possible to have a strongly first-order electroweak phase transition while simultaneously relaxing the tension with EDM experiments. The R-symmetry (and its small breaking) implies that the gauginos (and the neutralino LSP) are pseudo-Dirac fermions, which is relevant for both baryogenesis and DM. The singlet superpartner of the U(1)_Y pseudo-Dirac gaugino plays a prominent role in making the electroweak phase transition strongly first-order. The pseudo-Dirac nature of the LSP allows it to behave similarly to a Dirac particle during freeze-out, but like a Majorana particle for annihilation today and in scattering against nuclei, thus being consistent with current constraints. Assuming a standard cosmology, it is possible to simultaneously have a strongly first-order phase transition conducive to baryogenesis and have the LSP provide the full DM relic abundance, in part of the allowed parameter space. However, other possibilities for DM also exist, which are discussed. It is expected that upcoming direct DM searches as well as neutrino signals from DM annihilation in the Sun will be sensitive to this class of models. Interesting collider and Gravity-wave signals are also briefly discussed.Comment: 50 pages, 10 figure

Improved Measurement of the Pseudoscalar Decay Constant fDsf_{D_{s}}

We present a new determination of the Ds decay constant, f_{Ds} using 5 million continuum charm events obtained with the CLEO II detector. Our value is derived from our new measured ratio of widths for Ds -> mu nu/Ds -> phi pi of 0.173+/- 0.021 +/- 0.031. Taking the branching ratio for Ds -> phi pi as (3.6 +/- 0.9)% from the PDG, we extract f_{Ds} = (280 +/- 17 +/- 25 +/- 34){MeV}. We compare this result with various model calculations.Comment: 23 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

First Observation of τ→3πηντ\tau\to 3\pi\eta\nu_{\tau} and τ→f1πντ\tau\to f_{1}\pi\nu_{\tau} Decays

We have observed new channels for $\tau$ decays with an $\eta$ in the final state. We study 3-prong tau decays, using the $\eta\to\gamma\gamma$ and \eta\to 3\piz decay modes and 1-prong decays with two \piz's using the $\eta\to\gamma\gamma$ channel. The measured branching fractions are \B(\tau^{-}\to \pi^{-}\pi^{-}\pi^{+}\eta\nu_{\tau}) =(3.4^{+0.6}_{-0.5}\pm0.6)\times10^{-4} and \B(\tau^{-}\to \pi^{-}2\piz\eta\nu_{\tau} =(1.4\pm0.6\pm0.3)\times10^{-4}. We observe clear evidence for $f_1\to\eta\pi\pi$ substructure and measure \B(\tau^{-}\to f_1\pi^{-}\nu_{\tau})=(5.8^{+1.4}_{-1.3}\pm1.8)\times10^{-4}. We have also searched for $\eta'(958)$ production and obtain 90% CL upper limits \B(\tau^{-}\to \pi^{-}\eta'\nu_\tau)<7.4\times10^{-5} and \B(\tau^{-}\to \pi^{-}\piz\eta'\nu_\tau)<8.0\times10^{-5}.Comment: 11 page postscript file, postscript file also available through http://w4.lns.cornell.edu/public/CLN

Search for the Decays B^0 -> D^{(*)+} D^{(*)-}

Using the CLEO-II data set we have searched for the Cabibbo-suppressed decays B^0 -> D^{(*)+} D^{(*)-}. For the decay B^0 -> D^{*+} D^{*-}, we observe one candidate signal event, with an expected background of 0.022 +/- 0.011 events. This yield corresponds to a branching fraction of Br(B^0 -> D^{*+} D^{*-}) = (5.3^{+7.1}_{-3.7}(stat) +/- 1.0(syst)) x 10^{-4} and an upper limit of Br(B^0 -> D^{*+} D^{*-}) D^{*\pm} D^\mp and B^0 -> D^+ D^-, no significant excess of signal above the expected background level is seen, and we calculate the 90% CL upper limits on the branching fractions to be Br(B^0 -> D^{*\pm} D^\mp) D^+ D^-) < 1.2 x 10^{-3}.Comment: 12 page postscript file also available through http://w4.lns.cornell.edu/public/CLNS, submitted to Physical Review Letter

ΛΛˉ\Lambda\bar{\Lambda} Production in Two-Photon Interactions at CLEO

Using the CLEO detector at the Cornell $e^+e^-$ storage ring, CESR, we study the two-photon production of $\Lambda \bar{\Lambda}$, making the first observation of $\gamma \gamma \to \Lambda \bar{\Lambda}$. We present the cross-section for $\gamma \gamma \to \Lambda \bar{\Lambda}$ as a function of the $\gamma \gamma$ center of mass energy and compare it to that predicted by the quark-diquark model.Comment: 10 pages, postscript file also available through http://w4.lns.cornell.edu/public/CLN