Ultrasound confirmation of guidewire position may eliminate accidental arterial dilatation during central venous cannulation

<p>Abstract</p> <p>Background</p> <p>Ultrasound guidance during central line insertion has significantly reduced complications associated with this procedure and has led to it being incorporated as standard of care in many institutions. However, inadvertent arterial penetration and dilation remains a problem despite ultrasound guidance and can result in significant morbidity and even mortality. Dynamic ultrasound confirmation of guidewire position within the vein prior to dilation may help to prevent and even eliminate this feared complication.</p> <p>Methods</p> <p>A prospectively collected database of central line insertions for one author utilizing this novel technique was retrospectively reviewed for all incidents of arterial dilation over a period from September 2008 to January 2010.</p> <p>Results</p> <p>During the study period 53 central lines were inserted with no incidents of arterial dilation.</p> <p>Conclusions</p> <p>Ultrasound confirmation of guidewire position has the potential to reduce or eliminate the morbidity and mortality of arterial dilation during central line placement.</p

Intakes of vegetables and related nutrients such as vitamin B complex, potassium, and calcium, are negatively correlated with risk of stroke in Korea

Consumption of vegetables and fruits is associated with a reduced risk of stroke, but it is unclear whether their protective effects are due to antioxidant vitamins or folate and metabolically related B vitamins. The purpose of the study was to test the hypothesis that intake of fruits and vegetables, which are major sources of antioxidant and vitamin B complex vitamins, reduces the risk of stroke. Cases consisted of patients diagnosed with first event of stroke (n = 69). Controls (n = 69) were age-, sex-, and body mass index-matched to cases. Multivariable-adjusted regression analysis showed that subjects who ate four to six servings of vegetable per day had a 32% reduction in the risk of stroke, and those with more than six servings per day had a reduction of 69% after adjusting for age, sex, BMI, and family history of stroke. Intakes of total fat, plant fat, calcium, potassium, vitamin B1, vitamin B2, vitamin B6, niacin, and folate were significantly and negatively associated with the risk of stroke. Although the trend was not significant, stroke risk was reduced in the second quartile (1.21-2.66 servings per week) of fish intake. However, intake of fruits (average daily intake of 1.0 serving) and antioxidant vitamins such as carotene, vitamin C, and vitamin E was not associated with the risk of stroke. In conclusion, our observational study suggests that intake of fat and vegetables, rich sources of vitamin B complex, calcium, and potassium may protect against stroke

What are the main inefficiencies in trial conduct : a survey of UKCRC registered clinical trials units in the UK

BACKGROUND: The UK Clinical Research Collaboration (UKCRC) registered Clinical Trials Units (CTUs) Network aims to support high-quality, efficient and sustainable clinical trials research in the UK. To better understand the challenges in efficient trial conduct, and to help prioritise tackling these challenges, we surveyed CTU staff. The aim was to identify important inefficiencies during two key stages of the trial conduct life cycle: (i) from grant award to first participant, (ii) from first participant to reporting of final results. METHODS: Respondents were asked to list their top three inefficiencies from grant award to recruitment of the first participant, and from recruitment of the first participant to publication of results. Free text space allowed respondents to explain why they thought these were important. The survey was constructed using SurveyMonkey and circulated to the 45 registered CTUs in May 2013. Respondents were asked to name their unit and job title, but were otherwise anonymous. Free-text responses were coded into broad categories. RESULTS: There were 43 respondents from 25 CTUs. The top inefficiency between grant award and recruitment of first participant was reported as obtaining research and development (R&D) approvals by 23 respondents (53%), contracts by 22 (51%), and other approvals by 13 (30%). The top inefficiency from recruitment of first participant to publication of results was failure to meet recruitment targets, reported by 19 (44%) respondents. A common comment was that this reflected overoptimistic or inaccurate estimates of recruitment at site. Data management, including case report form design and delays in resolving data queries with sites, was reported as an important inefficiency by 11 (26%) respondents, and preparation and submission for publication by 9 (21%). CONCLUSIONS: Recommendations for improving the efficiency of trial conduct within the CTUs network include: further reducing unnecessary bureaucracy in approvals and contracting; improving training for site staff; realistic recruitment targets and appropriate feasibility; developing training across the network; improving the working relationships between chief investigators and units; encouraging funders to release sufficient funding to allow prompt recruitment of trial staff; and encouraging more research into how to improve the efficiency and quality of trial conduct

Biomarker-guided trials: Challenges in practice.

Biomarker-guided trials have drawn considerable attention as they promise to lead to improvements in the benefit-risk ratio of treatments and enhanced opportunities for drug development. A variety of such designs have been proposed in the literature, many of which have been adopted in practice. Implementing such trial designs in practice can be challenging, and identifying those challenges was the main objective of a workshop organised by the MRC Hubs for Trials Methodology Research Network's Stratified Medicine Working Group in March 2017. Participants reflected on completed and ongoing biomarker-guided trials to identify the practical challenges encountered. Here, the key challenges identified during the workshop including those related to funding, ethical and regulatory issues, recruitment, monitoring of samples and laboratories, biomarker assessment, and data sharing and resources, are discussed. Despite the complexities often associated with biomarker-guided trials, the workshop concluded that they can play an important role in advancing the field of personalised medicine. Therefore, it is important that the practical challenges surrounding their implementation are acknowledged and addressed

Reply to editorial and commentaries on Steele, Al-Mufti, Augustyn, Chandrajith, Coghlan, Coulson et al. (2018) "Cause of Cambrian explosion - Terrestrial or cosmic?"

No abstract availabl

Reply to commentary by R Duggleby (2019)

Duggleby (2018) has made a numerical analysis of some aspects of the wide range of phenomena we reviewed in Steele et al. (2018) and asserted " .that panspermia as proposed by Steele et al. (2018) is extremely implausible.” It seems to us that Duggleby has based his viewpoint on a quite narrow and specific model of Panspermia which he supposes to be active in the cosmos. Here we address both his conclusions and his numerical analysis. Our response therefore will be at two levels, his specific analysis and his general conclusions. In the specific section below we show that while Duggleby's numerical analysis appears in part correct it is, in the final analysis, quite irrelevant to Cosmic Panspermia. In the general response which follows we address his unsupported conclusion throughout his critique, namely that … " none of the examples mentioned by Steele et al. (2018) is decisive enough to allow no other explanation.

A multi-factorial analysis of response to warfarin in a UK prospective cohort

Background Warfarin is the most widely used oral anticoagulant worldwide, but it has a narrow therapeutic index which necessitates constant monitoring of anticoagulation response. Previous genome-wide studies have focused on identifying factors explaining variance in stable dose, but have not explored the initial patient response to warfarin, and a wider range of clinical and biochemical factors affecting both initial and stable dosing with warfarin. Methods A prospective cohort of 711 patients starting warfarin was followed up for 6 months with analyses focusing on both non-genetic and genetic factors. The outcome measures used were mean weekly warfarin dose (MWD), stable mean weekly dose (SMWD) and international normalised ratio (INR) > 4 during the first week. Samples were genotyped on the Illumina Human610-Quad chip. Statistical analyses were performed using Plink and R. Results VKORC1 and CYP2C9 were the major genetic determinants of warfarin MWD and SMWD, with CYP4F2 having a smaller effect. Age, height, weight, cigarette smoking and interacting medications accounted for less than 20 % of the variance. Our multifactorial analysis explained 57.89 % and 56.97 % of the variation for MWD and SMWD, respectively. Genotypes for VKORC1 and CYP2C9*3, age, height and weight, as well as other clinical factors such as alcohol consumption, loading dose and concomitant drugs were important for the initial INR response to warfarin. In a small subset of patients for whom data were available, levels of the coagulation factors VII and IX (highly correlated) also played a role. Conclusion Our multifactorial analysis in a prospectively recruited cohort has shown that multiple factors, genetic and clinical, are important in determining the response to warfarin. VKORC1 and CYP2C9 genetic polymorphisms are the most important determinants of warfarin dosing, and it is highly unlikely that other common variants of clinical importance influencing warfarin dosage will be found. Both VKORC1 and CYP2C9*3 are important determinants of the initial INR response to warfarin. Other novel variants, which did not reach genome-wide significance, were identified for the different outcome measures, but need replication

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT