3,943 research outputs found

    Xpert MTB/RIF - why the lack of morbidity and mortality impact in intervention trials?

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    : Compared with smear microscopy, the Xpert MTB/RIF assay (Xpert), with superior accuracy and capacity to diagnose rifampicin resistance, has advanced TB diagnostic capability. However, recent trials of Xpert impact have not demonstrated reductions in patient morbidity and mortality. We conducted a narrative review of Xpert impact trials to summarize which patient-relevant outcomes Xpert has improved and explore reasons for no observed morbidity or mortality reductions. We searched PubMed, Google Scholar, Cochrane Library and Embase and identified eight trials meeting inclusion criteria: three individually randomized, three cluster-randomized, and two pre-post trials. In six trials Xpert increased diagnostic yield of bacteriologically-confirmed TB from sputa and in four trials Xpert shortened time to TB treatment. However, all-cause mortality was similar between arms in all six trials reporting this outcome, and the only trial to assess Xpert impact on morbidity reported no impact. Trial characteristics that might explain lack of observed impact on morbidity and mortality include: higher rates of empiric TB treatment in microscopy compared with Xpert arms, enrollment of study populations not comprised exclusively of populations most likely to benefit from Xpert, and health system weaknesses. So far as equipoise exists, future trials that address past limitations are needed to inform Xpert use in resource-limited settings.<br/

    Impact of ethnicity and extreme prematurity on infant pulmonary function.

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    The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth ) and forced expired volume (FEV0.5 ) were obtained at ∼12 months post-term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23-27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30-36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37-42] weeks; 86% White mothers). Using reference equations based on identical equipment and techniques, results were expressed as z-scores to adjust for age, sex and body size. FEV0.5 was significantly lower in EP infants when compared with PTC (mean difference [95% CI]: -1.02[-1.60; -0.44] z-scores, P < 0.001), as was forced vital capacity (FVC) but there were no significant differences in FRCpleth or FEV0.5 /FVC ratio. FEV0.5 , FVC, and FEV0.5 /FVC were significantly lower in both preterm groups when compared with fullterm controls. On multivariable analyses of the combined preterm dataset: FEV0.5 at ∼1 year was 0.11 [0.05; 0.17] z-scores higher/week GA, and 1.28 (0.49; 2.08) z-scores lower in EP infants with prior BPD. Among non-white preterm infants, FEV0.5 was 0.70 (0.17; 1.24) z-scores lower, with similar reductions in FVC, such that there were no ethnic differences in FEV0.5 /FVC. Similar ethnic differences were observed among fullterm infants. These results confirm the negative impact of preterm birth on subsequent lung development, especially following a diagnosis of BPD, and emphasize the importance of taking ethnic background into account when interpreting results during infancy as in older subjects. Pediatr Pulmonol. © 2013 Wiley Periodicals, Inc

    Effect of floor type on the performance, physiological and behavioural responses of finishing beef steers

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    peer-reviewedBackground:The study objective was to investigate the effect of bare concrete slats (Control), two types of mats [(Easyfix mats (mat 1) and Irish Custom Extruder mats (mat 2)] fitted on top of concrete slats, and wood-chip to simulate deep bedding (wood-chip placed on top of a plastic membrane overlying the concrete slats) on performance, physiological and behavioral responses of finishing beef steers. One-hundred and forty-four finishing steers (503 kg; standard deviation 51.8 kg) were randomly assigned according to their breed (124 Continental cross and 20 Holstein–Friesian) and body weight to one of four treatments for 148 days. All steers were subjected to the same weighing, blood sampling (jugular venipuncture), dirt and hoof scoring pre study (day 0) and on days 23, 45, 65, 86, 107, 128 and 148 of the study. Cameras were fitted over each pen for 72 h recording over five periods and subsequent 10 min sampling scans were analysed. Results: Live weight gain and carcass characteristics were similar among treatments. The number of lesions on the hooves of the animals was greater (P < 0.05) on mats 1 and 2 and wood-chip treatments compared with the animals on the slats. Dirt scores were similar for the mat and slat treatments while the wood-chip treatment had greater dirt scores. Animals housed on either slats or wood-chip had similar lying times. The percent of animals lying was greater for animals housed on mat 1 and mat 2 compared with those housed on concrete slats and wood chips. Physiological variables showed no significant difference among treatments. Conclusions: In this exploratory study, the performance or welfare of steers was not adversely affected by slats, differing mat types or wood-chip as underfoot material

    Invariant Synthesis for Incomplete Verification Engines

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    We propose a framework for synthesizing inductive invariants for incomplete verification engines, which soundly reduce logical problems in undecidable theories to decidable theories. Our framework is based on the counter-example guided inductive synthesis principle (CEGIS) and allows verification engines to communicate non-provability information to guide invariant synthesis. We show precisely how the verification engine can compute such non-provability information and how to build effective learning algorithms when invariants are expressed as Boolean combinations of a fixed set of predicates. Moreover, we evaluate our framework in two verification settings, one in which verification engines need to handle quantified formulas and one in which verification engines have to reason about heap properties expressed in an expressive but undecidable separation logic. Our experiments show that our invariant synthesis framework based on non-provability information can both effectively synthesize inductive invariants and adequately strengthen contracts across a large suite of programs

    Ischaemic strokes in patients with pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia: associations with iron deficiency and platelets.

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    <div><p>Background</p><p>Pulmonary first pass filtration of particles marginally exceeding ∼7 µm (the size of a red blood cell) is used routinely in diagnostics, and allows cellular aggregates forming or entering the circulation in the preceding cardiac cycle to lodge safely in pulmonary capillaries/arterioles. Pulmonary arteriovenous malformations compromise capillary bed filtration, and are commonly associated with ischaemic stroke. Cohorts with CT-scan evident malformations associated with the highest contrast echocardiographic shunt grades are known to be at higher stroke risk. Our goal was to identify within this broad grouping, which patients were at higher risk of stroke.</p><p>Methodology</p><p>497 consecutive patients with CT-proven pulmonary arteriovenous malformations due to hereditary haemorrhagic telangiectasia were studied. Relationships with radiologically-confirmed clinical ischaemic stroke were examined using logistic regression, receiver operating characteristic analyses, and platelet studies.</p><p>Principal Findings</p><p>Sixty-one individuals (12.3%) had acute, non-iatrogenic ischaemic clinical strokes at a median age of 52 (IQR 41–63) years. In crude and age-adjusted logistic regression, stroke risk was associated not with venous thromboemboli or conventional neurovascular risk factors, but with low serum iron (adjusted odds ratio 0.96 [95% confidence intervals 0.92, 1.00]), and more weakly with low oxygen saturations reflecting a larger right-to-left shunt (adjusted OR 0.96 [0.92, 1.01]). For the same pulmonary arteriovenous malformations, the stroke risk would approximately double with serum iron 6 µmol/L compared to mid-normal range (7–27 µmol/L). Platelet studies confirmed overlooked data that iron deficiency is associated with exuberant platelet aggregation to serotonin (5HT), correcting following iron treatment. By MANOVA, adjusting for participant and 5HT, iron or ferritin explained 14% of the variance in log-transformed aggregation-rate (p = 0.039/p = 0.021).</p><p>Significance</p><p>These data suggest that patients with compromised pulmonary capillary filtration due to pulmonary arteriovenous malformations are at increased risk of ischaemic stroke if they are iron deficient, and that mechanisms are likely to include enhanced aggregation of circulating platelets.</p></div
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