359 research outputs found

    Measuring the Quality of Observational Study Data in an International HIV Research Network

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    Observational studies of health conditions and outcomes often combine clinical care data from many sites without explicitly assessing the accuracy and completeness of these data. In order to improve the quality of data in an international multi-site observational cohort of HIV-infected patients, the authors conducted on-site, Good Clinical Practice-based audits of the clinical care datasets submitted by participating HIV clinics. Discrepancies between data submitted for research and data in the clinical records were categorized using the audit codes published by the European Organization for the Research and Treatment of Cancer. Five of seven sites had error rates >10% in key study variables, notably laboratory data, weight measurements, and antiretroviral medications. All sites had significant discrepancies in medication start and stop dates. Clinical care data, particularly antiretroviral regimens and associated dates, are prone to substantial error. Verifying data against source documents through audits will improve the quality of databases and research and can be a technique for retraining staff responsible for clinical data collection. The authors recommend that all participants in observational cohorts use data audits to assess and improve the quality of data and to guide future data collection and abstraction efforts at the point of care

    Suicidal Behavior and Depression in Smoking Cessation Treatments

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    BACKGROUND: Two treatments for smoking cessation--varenicline and bupropion--carry Boxed Warnings from the U.S. Food and Drug Administration (FDA) about suicidal/self-injurious behavior and depression. However, some epidemiological studies report an increased risk in smoking or smoking cessation independent of treatment, and differences between drugs are unknown. METHODOLOGY: From the FDA's Adverse Event Reporting System (AERS) database from 1998 through September 2010 we selected domestic, serious case reports for varenicline (n = 9,575), bupropion for smoking cessation (n = 1,751), and nicotine replacement products (n = 1,917). A composite endpoint of suicidal/self-injurious behavior or depression was defined as a case with one or more Preferred Terms in Standardized MedDRA Query (SMQ) for those adverse effects. The main outcome measure was the ratio of reported suicide/self-injury or depression cases for each drug compared to all other serious events for that drug. RESULTS: Overall we identified 3,249 reported cases of suicidal/self-injurious behavior or depression, 2,925 (90%) for varenicline, 229 (7%) for bupropion, and 95 (3%) for nicotine replacement. Compared to nicotine replacement, the disproportionality results (OR (95% CI)) were varenicline 8.4 (6.8-10.4), and bupropion 2.9 (2.3-3.7). The disproportionality persisted after excluding reports indicating concomitant therapy with any of 58 drugs with suicidal behavior warnings or precautions in the prescribing information. An additional antibiotic comparison group showed that adverse event reports of suicidal/self-injurious behavior or depression were otherwise rare in a healthy population receiving short-term drug treatment. CONCLUSIONS: Varenicline shows a substantial, statistically significant increased risk of reported depression and suicidal/self-injurious behavior. Bupropion for smoking cessation had smaller increased risks. The findings for varenicline, combined with other problems with its safety profile, render it unsuitable for first-line use in smoking cessation

    Development and evolution of dentition pattern and tooth order in the Skates and Rays (Batoidea; Chondrichthyes)

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    Shark and ray (elasmobranch) dentitions are well known for their multiple generations of teeth, with isolated teeth being common in the fossil record. However, how the diverse dentitions characteristic of elasmobranchs form is still poorly understood. Data on the development and maintenance of the dental patterning in this major vertebrate group will allow comparisons to other morphologically diverse taxa, including the bony fishes, in order to identify shared pattern characters for the vertebrate dentition as a whole. Data is especially lacking from the Batoidea (skates and rays), hence our objective is to compile data on embryonic and adult batoid tooth development contributing to ordering of the dentition, from cleared and stained specimens and micro-CT scans, with 3D rendered models. We selected species (adult and embryonic) spanning phylogenetically significant batoid clades, such that our observations may raise questions about relationships within the batoids, particularly with respect to current molecular-based analyses. We include developmental data from embryos of recent model organisms Leucoraja erinacea and Raja clavata to evaluate the earliest establishment of the dentition. Characters of the batoid dentition investigated include alternate addition of teeth as offset successional tooth rows (versus single separate files), presence of a symphyseal initiator region (symphyseal tooth present, or absent, but with two parasymphyseal teeth) and a restriction to tooth addition along each jaw reducing the number of tooth families, relative to addition of successor teeth within each family. Our ultimate aim is to understand the shared characters of the batoids, and whether or not these dental characters are shared more broadly within elasmobranchs, by comparing these to dentitions in shark outgroups. These developmental morphological analyses will provide a solid basis to better understand dental evolution in these important vertebrate groups as well as the general plesiomorphic vertebrate dental condition

    Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

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    <p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan<sup>® </sup>manikin.</p> <p>Results</p> <p>The Airtraq<sup>® </sup>reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview<sup>® </sup>increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq<sup>® </sup>devices.</p> <p>Conclusion</p> <p>The Airtraq<sup>® </sup>laryngoscope performed more favourably than the Macintosh and Truview<sup>® </sup>devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

    Energy loss due to defect formation from \u3csup\u3e206\u3c/sup\u3ePb recoils in SuperCDMS germanium detectors

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    The Super Cryogenic Dark Matter Search experiment (SuperCDMS) at the Soudan Underground Laboratory studied energy loss associated with Frenkel defect formation in germanium crystals at mK temperatures using in situ 210Pb sources. We examine the spectrum of 206Pb nuclear recoils near its expected 103 keV endpoint energy and determine an energy loss of (6.08±0.18) %, which we attribute to defect formation. From this result and using TRIM simulations, we extract the first experimentally determined average displacement threshold energy of (19.7+0.6−0.5) eV for germanium. This has implications for the analysis thresholds of future germanium-based dark matter searches

    Comparison of the Airtraq® and Truview® laryngoscopes to the Macintosh laryngoscope for use by Advanced Paramedics in easy and simulated difficult intubation in manikins

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    <p>Abstract</p> <p>Background</p> <p>Paramedics are frequently required to perform tracheal intubation, a potentially life-saving manoeuvre in severely ill patients, in the prehospital setting. However, direct laryngoscopy is often more difficult in this environment, and failed tracheal intubation constitutes an important cause of morbidity. Novel indirect laryngoscopes, such as the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes may reduce this risk.</p> <p>Methods</p> <p>We compared the efficacy of these devices to the Macintosh laryngoscope when used by 21 Paramedics proficient in direct laryngoscopy, in a randomized, controlled, manikin study. Following brief didactic instruction with the Airtraq<sup>® </sup>and Truview<sup>® </sup>laryngoscopes, each participant took turns performing laryngoscopy and intubation with each device, in an easy intubation scenario and following placement of a hard cervical collar, in a SimMan<sup>® </sup>manikin.</p> <p>Results</p> <p>The Airtraq<sup>® </sup>reduced the number of optimization manoeuvres and reduced the potential for dental trauma when compared to the Macintosh, in both the normal and simulated difficult intubation scenarios. In contrast, the Truview<sup>® </sup>increased the duration of intubation attempts, and required a greater number of optimization manoeuvres, compared to both the Macintosh and Airtraq<sup>® </sup>devices.</p> <p>Conclusion</p> <p>The Airtraq<sup>® </sup>laryngoscope performed more favourably than the Macintosh and Truview<sup>® </sup>devices when used by Paramedics in this manikin study. Further studies are required to extend these findings to the clinical setting.</p

    First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector

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    We present the first limits on inelastic electron-scattering dark matter and dark photon absorption using a prototype SuperCDMS detector having a charge resolution of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 gram CDMS HV device). These electron-recoil limits significantly improve experimental constraints on dark matter particles with masses as low as 1 MeV/c2. We demonstrate a sensitivity to dark photons competitive with other leading approaches but using substantially less exposure (0.49 gram days). These results demonstrate the scientific potential of phonon-mediated semiconductor detectors that are sensitive to single electronic excitations

    Search for low-mass dark matter with CDMSlite using a profile likelihood fit

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    The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) searches for interactions between dark matter particles and germanium nuclei in cryogenic detectors. The experiment has achieved a low energy threshold with improved sensitivity to low-mass (/c2) dark matter particles. We present an analysis of the final CDMSlite data set, taken with a different detector than was used for the two previous CDMSlite data sets. This analysis includes a data salting method to protect against bias, improved noise discrimination, background modeling, and the use of profile likelihood methods to search for a dark matter signal in the presence of backgrounds. We achieve an energy threshold of 70 eV and significantly improve the sensitivity for dark matter particles with masses between 2.5 and 10 GeV/c2 compared to previous analyses. We set an upper limit on the dark matter-nucleon scattering cross section in germanium of 5.4×10−42 cm2 at 5 GeV/c2, a factor of ∼2.5 improvement over the previous CDMSlite result
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